potent antivirallere kısmi yanıtlı olgular · 2015-06-30 · evaluation of 3 years treatment...
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![Page 1: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/1.jpg)
Potent Antivirallere Kısmi Yanıtlı Olgular
Fatime Korkmaz
Konya Eğitim Araştırma Hastanesi
Kr Hepatit B de tedavi amacı
bull Siroz hepatoselluumller kanser ve karaciğer yetmezliği gibi uzun doumlnem komplikasyonları oumlnlemek ve yaşam kalitesini arttırmaktır
bull Karaciğer histolojisinin duumlzelmesi
bull HBe Ag Anti HBe serokonversiyonu
bull HBs Ag Anti HBs serokonversiyonu
TEDAVİNİN BAŞARISI Kalıcı HBV DNA negatifliğini sağlamak ALT duumlzeyinin normal sınırlarda kalması Virusun tam eradikasyonu ccDNA kalıcı
Tedavideki ilaccedillar yıllar iccedilindehellip
Akhan S etal Klimik Dergisi 2014 27(oumlzel sayı)2-18
OLGU 1 22 yaş erkek
ŞikayetiHikayesi Halsizlik son 2 aydır
4 yıl oumlnce HBs Ag pozitif takip yaptırmamış
3-4 aydır antidepresan kullanıyor (Milnasipran 50 mg)
Aile oumlykuumlsuuml Anne ve diğer kardeşte HBV
Fizik Muayene zayıf goumlruumlnuumlmluuml (ağırlık60 kg boy172 cm BKİ= 202)
İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 2: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/2.jpg)
Kr Hepatit B de tedavi amacı
bull Siroz hepatoselluumller kanser ve karaciğer yetmezliği gibi uzun doumlnem komplikasyonları oumlnlemek ve yaşam kalitesini arttırmaktır
bull Karaciğer histolojisinin duumlzelmesi
bull HBe Ag Anti HBe serokonversiyonu
bull HBs Ag Anti HBs serokonversiyonu
TEDAVİNİN BAŞARISI Kalıcı HBV DNA negatifliğini sağlamak ALT duumlzeyinin normal sınırlarda kalması Virusun tam eradikasyonu ccDNA kalıcı
Tedavideki ilaccedillar yıllar iccedilindehellip
Akhan S etal Klimik Dergisi 2014 27(oumlzel sayı)2-18
OLGU 1 22 yaş erkek
ŞikayetiHikayesi Halsizlik son 2 aydır
4 yıl oumlnce HBs Ag pozitif takip yaptırmamış
3-4 aydır antidepresan kullanıyor (Milnasipran 50 mg)
Aile oumlykuumlsuuml Anne ve diğer kardeşte HBV
Fizik Muayene zayıf goumlruumlnuumlmluuml (ağırlık60 kg boy172 cm BKİ= 202)
İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 3: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/3.jpg)
Tedavideki ilaccedillar yıllar iccedilindehellip
Akhan S etal Klimik Dergisi 2014 27(oumlzel sayı)2-18
OLGU 1 22 yaş erkek
ŞikayetiHikayesi Halsizlik son 2 aydır
4 yıl oumlnce HBs Ag pozitif takip yaptırmamış
3-4 aydır antidepresan kullanıyor (Milnasipran 50 mg)
Aile oumlykuumlsuuml Anne ve diğer kardeşte HBV
Fizik Muayene zayıf goumlruumlnuumlmluuml (ağırlık60 kg boy172 cm BKİ= 202)
İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 4: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/4.jpg)
Akhan S etal Klimik Dergisi 2014 27(oumlzel sayı)2-18
OLGU 1 22 yaş erkek
ŞikayetiHikayesi Halsizlik son 2 aydır
4 yıl oumlnce HBs Ag pozitif takip yaptırmamış
3-4 aydır antidepresan kullanıyor (Milnasipran 50 mg)
Aile oumlykuumlsuuml Anne ve diğer kardeşte HBV
Fizik Muayene zayıf goumlruumlnuumlmluuml (ağırlık60 kg boy172 cm BKİ= 202)
İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
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OLGU 1 22 yaş erkek
ŞikayetiHikayesi Halsizlik son 2 aydır
4 yıl oumlnce HBs Ag pozitif takip yaptırmamış
3-4 aydır antidepresan kullanıyor (Milnasipran 50 mg)
Aile oumlykuumlsuuml Anne ve diğer kardeşte HBV
Fizik Muayene zayıf goumlruumlnuumlmluuml (ağırlık60 kg boy172 cm BKİ= 202)
İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 6: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/6.jpg)
Laboratuvar Bulguları
bull ALT 137 UL bull AST 88 UL bull GGT 35 UL bull Tbiluumlribin12 mgdl bull Tprotein 82 mgdL bull Albuumlmin 48 mgdL bull Kreatinin 08mgdL bull PTZ93 sn INR1 bull AFP 23 ngml bull Trombosit 220 000 mL
bull Anti HBe Negatif bull Anti HBcIgM Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
1 250 000 000 IUml
a
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 7: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/7.jpg)
UumlST BATIN USG
Normal bulgular
KC BİYOPSİ (Modifiye ISHAK)
bull Periportal alanda orta şiddete50 den az piecemal nekroz (3)
bull Fokal konfluent nekroz (1)
bull İntralobuumller alanda 2-4 fokal
litik nekrozfokal inflamasyon (2)
bull Portal alanda orta derecede inflamasyon (2)
bull Portal alanda fibrozis (2)
HAİ8 E2
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 8: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/8.jpg)
Tedavi seccedilenekleri rehberler EASL 2012
APASL 2012
AASLD 2009
VHSD 2011
KLİMİK ndashVHCcedilG 2014
HBe Ag ( + )
HBV DNA IUml
ge 20 000 ge 20000 ge 20 000 gt 2000 gt 2000- 20000
ALT UL
gt 2 kat gt 2-5 kat
gt 2 kat
gt normal gt 2 kat
KC BİYOPSİ gt2000 biyopsi ile ge A2- ge F2 gt20000 biyopsi olmadan da
Ortaşiddetli İnflamasyon
Opsiyonlu Ortaşiddetli İnflamasyon Belirgin fibrozis
HAİge4 E ge 2 Biyopsi oumlnerilir
OumlNERİ Tedavi et 3 - 6 ay ara ile ALT HBe Ag izlemi Tedavi et
1-3 ay ara ile ALT HBe Ag izlemi Tedavi et
Tedavi et Tedavi et
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 9: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/9.jpg)
Tedavi seccedilimi Entekavir 05 mg guumln ilehellip
bull DNA polimerazın potent inhibitoumlrlerinden
bull Nuumlkleozid analoğu
bull Genetik bariyeri yuumlksek
bull Yan etki youmlnuumlnden rahat
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 10: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/10.jpg)
EASL 2012
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 11: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/11.jpg)
EASL KAYNAKLARI
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 12: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/12.jpg)
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE CHRONIC HEPATITIS B PATIENTS Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime KORKMAZ Konya Meram Research and Education Hospital
HBV DNA 1Year 2 Year 3 Year
HBeAg (+)
n15
13 (866) 15(1000) 15(1000)
HBeAg (-)
n36
25 ( 694) 33 (916) 35 (972)
APASL 2013 POSTER
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 13: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/13.jpg)
EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVIR NAIVE
CHRONIC HEPATITIS B PATIENTS
Fatma KACAR Nazlım AKTUĞ DEMİR Halil KARATAŞ Mehmet OumlZCAN Fatime
KORKMAZ
Konya Meram Research and Education Hospital
Purpose In this study 3 years treatment results of 51 chronic hepatitis B patients treated with
05 mgday entacavir
Method This study included 51 patients admitted to Infectious Diseases clinic of Konya
Research and Education Hospital between January 2008 and September 20121 Data were
recorded to SPSS 160 package program and chi-square test was used for statistical evaluation
of cathegorical variables plt005 was considered as statistically significant
Findings Thirty three (647) patients were males 18 (353) were females and mean age
was 41 plusmn 168 HBeAg was positive in 15 (295) patients and Anti-HBe was positive in 36
(705) patients Median HBV DNA value was 86424000 (21000-19937832620) IUMl and
median alanine aminotransferase (ALT) value was 97(28-468) ul Three years treatment
responses of patients are given in Table 1
Table 1 Treatment Responses of Patients Versus Years
1Year 2Year 3Year
HBV DNA
(IUml)
38(745) 48(941) 50(98)
ALT(UL) 40(784) 49(96) 50(98)
Rate of turning of HBV DNA test to negative and rate of ALT normalisation in HBeAg
positive Anti-Hbe positive patients are shown in Table 2 and Table 3
Table 2 Rate of Turning of HBV DNA Test to Negative in HBeAg positive and Anti-
Hbe Positive Patients
HBV DNA 1Year 2 Year 3 Year
HBeAg (+) 13 (866) 15(1000) 15(1000)
HBeAg (-) 25 ( 694) 33 (916) 35 (972)
Table 3 Rate of ALT Normalisation in HBeAg Positive and Anti-Hbe Positive Patients
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 14: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/14.jpg)
Kronik B Hepatitinde Entekavir Kullanımının Etkinliği ile İlgili Tuumlrkiye Kaynaklı Ccedilalışmaların Meta-Analizi
16
643
803
898 907
996
50
60
70
80
90
100
6 12 24 36 48
Suumlre (ay)
Daha oumlnce tedavi almamış hastalarda virolojik yanıt
Akarca US ve ark
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 15: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/15.jpg)
TEDAVİ SEYRİ
AY - HAFTA ALT U L
HBV DNA İUml
0 - 137 1 250 000 000
3 (12) 60
6 (24) 43 44600
9 (36) 32 33659
Biyokimyasal yanıt 6 ay
Kısmi virolojik yanıt
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 16: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/16.jpg)
EASL 2012 KISMİ VİROLOJİK YANIT YOumlNETİMİ
bull Youmlnetim tartışmalı
bull 48 Haftada HBV DNA duumlşme eğilimde ise aynı ajanla devam edilebilir
(ETV ya da TDF) (B1)
bull 2 lsquoli tedavi (C2)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 17: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/17.jpg)
24 Haftaya goumlre kısmi viral yanıtta yol haritası
Tedavi 24 hafta
Ccedilapraz direnci olmayan diğer ilacı ekle
3 ayda bir kontrol et
Kısmi yanıt 60 - lt 2000 IUml
300 -10000 kopyaml
Keeff et alClinical Gastroenterology and hepatology 2007 5 s890-97
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 18: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/18.jpg)
VİRAL YUumlKUuml YUumlKSEK HBE AG(+) HASTADA ENTEKAVİR SECcedilİMİ UYGUN MU Efficacy of entecavir treatment for up to 96 weeks in nucleoside-naive HBeAg-positive chronic hepatitis B patients with high viral load
TEDAVİ HAFTASI
VİROLOJİK YANIT HBV DNA gt 10 log 9 kopyaml
VİROLOJİK YANIT HBV DNA lt 10 log 9 kopyaml
p
48 42 6734 0006
72 62 8571 0007
96 68 8571 0037
bull 99 HBe Ag(+) hastanaif
bull 50rsquosi yuumlksek viral yuumlk
gt 10 log 9 kopyaml
bull 49 lsquou yuumlksek olmayan VY
lt 10 log 9 kopya ml
bull Virolojik yanıt lt300 kopyaml
Yan LB et alClin Res Hepatol Gastroenterol 2014
SONUCcedil Başlangıccediltaki viral yuumlkuumln yuumlksek Olması virolojik yanıt iccedilin negatif bir belirteccedil
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 19: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/19.jpg)
Viral yuumlk ge 7 log IUml
Viral yuumlk lt 7 log IUml
150 NA naif hasta LAM69 ETV35 TDF46
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 20: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/20.jpg)
Tedaviye TDF eklendihelliphellip
AYLAR 0 ETV
3 ETV
6 ETV
9 ETV+TDF
12 ETV+ TDF
ALT UL 137 60 43 32 26
HBV DNA IUml
1 250 000 000 44600 33659 773
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 21: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/21.jpg)
2rsquoli tedavi suumlresi helliphellip Sonra monoterapi bull KESİN VERİ YOK DENEYİMLER GENELLİKLE 24-48 HAFTADA
(CcedilOĞUL İLACcedil DİRENCİ YOKSA) VİRAL SUumlPRESYON SAĞLANIP MONOTERAPİ YOumlNUumlNDE
DİRENCcedilLİ VİUSTA DEVAMhellip
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 22: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/22.jpg)
2 li sonrası TDF monoterapisi
bull Eur J Gastroenterol Hepatol 2015 Apr 21 [Epub ahead of print]
bull Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy
bull Kim LH1 Chaung KT Ha NB Kin KC Vu VD Trinh HN Nguyen HA Nguyen MH
bull Author information
bull Abstract
bull OBJECTIVES
bull It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV Our goal was to examine virologic outcomes in such patients
bull METHODS
bull This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy who were switched back to monotherapy with either ETV (n=16) or TDF (n=18) or continued on combination therapy (n=23) The majority of patients were Asian (91) and male (65) with a mean age of 41plusmn12 years
bull RESULTS
bull The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs 39 P=0004) Patients who remained on ETV+TDF also had virologic breakthrough due to either confirmed or suspected nonadherence On multivariate analysis inclusive of age sex and hepatitis B virus DNA levels at initiation of combination therapy ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 1127 P=003) as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 602 P=003)
bull CONCLUSION
bull TDF monotherapy especially in those who have had CVS for at least 12 months on combination therapy may be considered for some ETV partial responders who have achieved CVS with combination therapy given the financial advantage and convenience of monotherapy
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 23: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/23.jpg)
Olgu 2
43 yaş erkek işccedili
ŞikayetiHikayesi Yakınması yok Tarama sırasında HBs Ag(+)
Aile oumlykuumlsuuml Oumlzellik yok
Fizik Muayene İkteri yok
Karaciğer dalak palpe edilmiyor traube accedilık asit yok
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 24: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/24.jpg)
LABORATUVAR BULGULARI (Mart 2008)
bull ALT 75 - 282 UL bull AST 51 - 161 UL bull GGT 55 UL bull Tbiluumlribin 06 mgdl bull Tprotein 78 mgdL bull Albuumlmin 4 mgdL bull Kreatinin 11 mgdl bull PTZ 129 sn INR103 bull AFP 62 ngml bull Trombosit 182 000 mL
bull HBs Ag Pozitif bull Anti HBe Pozitif bull HBe Ag Negatif bull Anti HDV bull Anti HCV Negatif bull Anti HIV bull Anti HAV IgG Pozitif
HBV DNA gt 100 000 000 kopyaml
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 25: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/25.jpg)
İlk Takipte ALT artışı
bull Anti HBc IgM Negatif
bull CMV EBV HSV koinf yok
bull Demir bakır depo hst yok
bull İmmuumln marker (ANAAMA)
bull Negatif
Mart Nisan Biyopsi
mayıs Haziran Tedavi başlandı
ALT UL 75 282 464 - 190
182
AST Uml
51 161 269- 77 75
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 26: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/26.jpg)
TEDAVİ SECcedilENEĞİ
bull USG Normal bulgular
bull KARACİĞER BİYOPSİ (Mod ISHAK)
bull HAİ 10 E1
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 27: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/27.jpg)
TEDAVİ KARARI Tenofovir disoproxil 245 mg (Haziran 2008)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 28: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/28.jpg)
TDF TEDAVİ İZLEMİ 3 ay biyokimyasal yanıt 6ay kısmi VY 12ay VY
0
20
40
60
80
100
120
140
160
180
200
0 3 6 9 12
ALT UL
AYLAR
AYLAR 0 3 6 9 12
ALT UL 182 30 25 22 26
HBV DNA IUml 100000000 kopya 2000 kopya 35 IUml
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 29: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/29.jpg)
ANCAK HASTA MUTSUZ-GİS YAN ETKİ
Tenofovir yan etkiler bull Nadiren laktik asidoz bulguları
bull Sarılık
bull Nadir bulantı kusma mide ağrısı gaz-şişkinlik
bull Uyku problemi baş doumlnmesi
bull Kaşıntı
bull Uzun suumlreli kullanımda renal fonksiyon bozukluğu
bull laquo laquo osteopeni-poroz
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 30: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/30.jpg)
GASTRİK YAKINMALAR İCcedilİN ENDOSKOPİ
bull OumlZEFAJİT
bull LES DİSFONKSİYONU
bull PANGASTRİT
bull PPI
bull ANTİASİT
bull TEDAVİ 48 HF (1 YIL) HASTA İSTEĞİ İLE İLACcedil DEĞİŞİMİ
bullENTEKAVİR
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 31: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/31.jpg)
TDF ETV tedavi seyiri
bull
bull viral kırılma bull ilaccedil uyumu
AYLAR ALT UL
HBV DNA IUml
0 26 35
3 28
6 38 lt 10
12 33 lt 10
18 40
24 115 259 000
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 32: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/32.jpg)
Viral kırılmada EASL 2012 oumlnerisi
bullLAMLdT ADVİlaca uyum varsa direnccedil duumlşuumlnuumllmeli
bullPotent ilaccedillarda hasta uyumsuzluğu
bullCcedilok duumlşuumlk ihtimal entekavir direnci
bullEntecavir direncinde TDF değişimekleme
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 33: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/33.jpg)
HASTAMIZDA DURUM
bull Hastanın ağabeyi vefat etmiş
bull ETV lsquoi aksatmış ama kesmemiş
bull ETV direnci baktırmadık (2011)
bull ETV lsquoye TDF EKLENEREK DEVAMhelliphellip
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 34: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/34.jpg)
ETV+ TDF 6 AYLIK SEYİR
ALT 115 55 UL
HBV DNA 240 IUml
YENİDEN TENOF0VİR MONOTERAPİ
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 35: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/35.jpg)
TENOFOVİRLE DEVAM AYLAR ALT UL HBV
DNA IUml
0 (42) 55 240
6 (48) 32 192
12 (54) 24 NEGATİF
18 (60) 18 507 VİRAL KIRILMA
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 36: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/36.jpg)
Sequence Information
Identifier Konya EAH N A HBV
Genotype D
Dual Infection No indication of dual infection was found (100
confidence)
Subgenotype D1 (similarity to subgenotype profile = 9865)
Included RT
domain codons
82 - 243 (similarity to reference = 9815)
Included SHB
protein codons
74 - 227 (similarity to reference = 9805)
Mutations RT
domain
H124Y Y135S Q215S (LAM ve ADV ile ilişkili
kompansatuvar - viral replikasyonu onarıcıarttırıcı-
mutasyon)
Mutations SHB
protein
T127P S207R I208T
Escape mutations
SHB protein
Drug Resistance
Drugs
Scored mutations
Resistance analysis
Lamivudine Zeffixreg
none
susceptible
Adefovir Hepserareg
none
susceptible
Entecavir Baracludereg
none
susceptible
Tenofovir DF
none
susceptible
Telbivudine Tyzekareg Sebivoreg
none
susceptible
VHCcedilG ULUSAL HBV İLACcedil DİRENCİ PROJESİ
DoccedilDrMurat SAYAN Kocaeli Uumlniversitesi Hastanesi Merkez Laboratuvarı PCR Uumlnitesi
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 37: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/37.jpg)
TENOFOVİRE DEVAMhellip VE NİHAYET hellip 2013 - 2015 AYLAR ALT UL HBV DNA
IUml
18 (60) 18 507
21 (63) 17 20
24 (66) 18 NEGATİF
30 (72) 20 NEGATİF
36 (78) 19 NEGATİF
bull HBs Ag Pozitif
bull Anti HBs Negatif
bull HBe Ag Negatif
bull Anti HBe Pozitif
bull UumlRE 42
bull Kreatinin 111
bull AFP 3
bull Plt 280 000
bull USG Normal
bull Kemik dansitometre patolojiksınırda değil
TEŞEKKUumlR EDERİM
![Page 38: Potent Antivirallere Kısmi Yanıtlı Olgular · 2015-06-30 · EVALUATION OF 3 YEARS TREATMENT RESULTS OF ENTECAVI R NAI VE CHRONIC HEPATITIS B PATIENTS )DWPD.$&$5 1D]OÕP$.78ö'(0ø5](https://reader033.vdocuments.pub/reader033/viewer/2022042006/5e7035ddd18c2c657135bb2a/html5/thumbnails/38.jpg)
TEŞEKKUumlR EDERİM