combine conference 2011.05.18 r4 李思穎 / vs 賴俊夫. a 48-year-old woman with vomiting with...
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Combine Conference2011.05.18
R4 李思穎 / VS 賴俊夫
A 48-year-old woman with vomiting with blood clot for 10 days
Past History
• Systemic disease– Hypertension for 10+ year– Chronic hepatitis B related liver cirrhosis, Child A– Coronary artery disease, s/p POBA– Peptic ulcer disease
• Regular medications– Inderal(10mg) 1# BID– Norvasc(5mg) 1# BID
Personal History
• Surgical History– Gallbladder stone s/p cholecystectomy in 2008
• Allergy: No known drug allergies• Occupation: nil• Travel: no travel in recent 3 months• Animal contact: no• Smoking: denied• Drinking: denied• Betel nuts: denied
Family History
48-year-old55-year-old
24-year-old 23-year-old 16-year-old
HBV carrier
Present Illness
• Nausea, poor appetite and vomiting with blood clot for 10 days
• Visit NTUH ER– TPR=36.7C/71/18– Bp=136/94
2011/2/22
Physical ExaminationGeneral
appearanceBL: 163 cm, BW: 80.1 kgConsciousness: Clear and alert, E4M6V5
Vital signsT/P/R: 36.7/83/18, BP: 140/88 mmHg, SpO2=100% under room air
HEENT
Grossly normalConjunctiva: not pale, Sclera: icteric Pupils: isocoric, 3.0/3.0 mm Light reflex: bilateral promptNo gum bleeding
Neck Supple, JVE(-), LAP(-), Goiter(-)
ChestSymmetric expansion, deformity(-), Breath sounds: bilateral clear, wheezing(-), crackles(-)
Physical Examination
Heart RHB, no murmur, no extra-sounds
Abdomen
Soft , Tenderness(+, epigastric), Rebound(-),
Muscle guarding(-), Normal lung liver border Liver: impalpable, Spleen: impalpable Shifting dullness(-), Central obesity(-) Striae(-), Bowel sound: normoactive
ExtremitiesFreely movable, Clubbing (-), Cyanosis(-), Pitting edema(-), symmetric pulsations
Skin Petechiae(-), Ecchymoses(-)
NE No specific finding
• Hemogram
Date RBC Hb Hct MCV MCH MCHC Plt WBC
106/μL g/dL % fL pg g/dL 103/μL /μL
2/22 4.83 13.2 41.4 85.7 27.3 31.9 116 4640
Date Blast Promyl/myelo
Meta Seg/ Band
Eos Baso Mono Lym/Aty. lym
% % % % % % % %
2/22 0 0/0 0 61.0 / 0 2.8 0.4 6.5 29.3 / 0
Lab
Lab
• Biochemistry and Electrolyte
• Coagulation profile
Date Alb T/D-Bilirubin ALP r-GT AST ALT Amy Lip
g/dL mg/dL IU/L IU/L IU/L IU/L IU/L IU/L
2/22 3.7 2.64/1.76 328 163 677 425 106 30
Date BUN Cr Na K Ca Mg
mg/dL mg/dL mmol/L mmol/L mmol/L mg/dL
2/22 7 0.73 137 4.1 1.98 0.74
Date PT PT INR PTT
sec sec
2/22 14.1 1.29 31.9
• Urine analysisDate Sp.
Gr.pH Protein Glu. Ketones O.B. Bil Urobil.
mg/dL mg/dL mg/dL mg/dL mg/dL EU/dL
2/12 1.008 7.5 - - - 3+ - 2.0
RBC WBC EpithCell
Cast Crystal Nitrite Others Color Turbidity
/HPF /HPF /HPF /LPF
5-10 0-2 0-2 - - - - Yellow Clear
Lab
CXR (2011/02/22)
Abdominal Ultrasound
Hepatitis Profile
檢查項目 數值 單位 標準值Alpha-Fetoprotein 7.08 ng/ml <20
HBeAg Reactive(532.374) S/CO
Anti-HBe Nonreactive(23.95)
IgM-Anti-HAV Nonreactive(0.34)
Anti-Hepatitis C Virus
Nonreactive(0.06)
HBV viral load >1.0 E+09 IU/ml 1IU=3.41 copies
Present Illness
• Chronic hepatitis B with flare up– Start Lamivudine
• Hepatic encephalopathy– Switch to Entecavir– Start pre-liver transplantation evaluation
2011/2/25
2011/3/02
2011/3/6~3/21Plasma Exchange
2011/3/6~3/21Plasma Exchange
2011/3/10~SLED
0222 0310 0323
2011/3/6~3/21Plasma Exchange
2011/3/23Liver Transplantation
2011/3/23Liver Transplantation
2011/3/6~3/21Plasma Exchange
2011/3/28 B/C: candida albicans
2011/3/23Liver Transplantation
2011/3/6~3/21Plasma Exchange
2011/4/06Explore laparotomyLiver biopsy: no rejection
2011/3/23Liver Transplantation
2011/3/6~3/21Plasma Exchange
2011/4/06Explore laparotomyLiver biopsy: no rejection
2011/3/6~3/21Plasma Exchange
2011/3/23Liver Transplantation
2011/4/06Explore laparotomyLiver biopsy: no rejection
2011/3/10~SLED cSLED(4/3-4/12)SLED IHD
0406 04180310 0323
2011/3/23Liver Transplantation
2011/3/10~SLED cSLED(4/3-4/12)SLEDIHD
0222
2011/3/23Liver Transplantation
2011/3/10~SLED cSLED(4/3-4/12)SLED IHD
2011/3/23Liver Transplantation
2011/3/10~SLED cSLED(4/3-4/12)SLED IHD
2011/3/6~3/21Plasma Exchange
2011/3/23Liver Transplantation
2011/4/06Explore laparotomyLiver biopsy: no rejection
2011/3/10~SLED cSLED(4/3-4/12)SLED IHD(-5/6)Hold
Discussion
1. Renal prognosis after liver transplantation for hepatorenal syndrome
2. Indication of simultaneous liver-kidney transplantation
Abbreviation
• LTX: Liver transplantation• LTA: Liver transplant alone• OLT: Orthotopic liver transplantation• KTA: Kidney transplant alone• LKTX: Liver-kidney transplants• CLKT: Combined liver and kidney transplantation• SLK: Simultaneous liver and kidney• KALT: Kidney transplantation after liver transplantation• HRS: Hepatorenal syndrome
Discussion
1. Renal prognosis after liver transplantation for hepatorenal syndrome
2. Indication of simultaneous liver-kidney transplantation
• Approximately 20% of patients undergoing liver transplantation (LTx) demonstrate acute or chronic renal insufficiency
Model for end-stage liver disease (MELD)
• Adopted by UNOS(United Network for Oragn Sharing) in 2002 as the basis for deceased donor liver allocation for adult patients
Transplantation, 2011
Model for end-stage liver disease (MELD)
www.unos.org
LKTx in UNOS Data
Transplantation, 2011
MELD Score
• Predict mortality and choose candidates most in need of LTx
• 3.8[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.6[Ln serum creatinine (mg/dL)] + 6.4
Pre-MELD vs Post-MELD Era
Patient Survival Graft Survival
Post-MELD era ~ Mean MELD: 20.5Pre-MELD era ~ Mean MELD: 17.0
Aliment Pharmacol Ther 2005; 21: 169
• Renal failure before LTx has been reported to predict an increased risk of postoperative renal failure, infection, and death
Renal Function in Liver Disease
• Serum creatinine: unreliable(overestimate)– lower muscle mass– decreased hepatic synthesis of creatine, the
precursor of creatinine– increased tubular secretion of creatinine
• Women will have a lower MELD score than men because of a smaller muscle mass
Transplantation, 2011
Acute Kidney Injury
• Cause– Hepatorenal syndrome(HRS): 17%– Acute tubular necrosis– Hypovolemia-associated hemorrhage– Infection– ……
Hepatorenal Syndrome
• The development of acute renal failure in a patient who usually has advanced liver disease due to cirrhosis, severe alcoholic hepatitis or metastatic tumor
Diagnostic Criteria -1
• Major criteria– Chronic or acute liver disease with advanced hepatic
failure and portal HTN– Low GFR ( crea> 1.5mg/dL or 24hr Ccr< 40 mL/min )– Absence of shock, current or recent treatment with
nephrotoxic drugs, fluid losses, or ongoing bacterial infection
– No improvement after diuretics withdraw & hydration with 1.5 L of isotonic saline
– Proteinuria < 500mg/day and no ultrasonographic evidence of obstructive uropathy or parenchymal renal disease
Gut 2007;56: 1310-1318
Diagnostic Criteria -2
• Minor criteria– Urine volume < 500mL/day – Urine Na < 10 mEq/L– Urine osmo greater than plasma osmo– Urine RBC < 50/HPF – Serum Na< 130 mEq/L
Gut 2007;56: 1310-1318
Current Diagnostic Criteria
• Chronic or acute liver disease with advanced hepatic failure and portal HTN
• Low GFR ( crea> 1.5mg/dL)• Absence of shock, current or recent treatment with
nephrotoxic drugs, fluid losses• No improvement after diuretics withdraw & hydration
with Albumin 1g/kg/BW (up to a maximum 100g)• Proteinuria < 500mg/day and no ultrasonographic
evidence of obstructive uropathy or parenchymal renal disease
Gut 2007;56: 1310-1318
Classification
• HRS Type 1
• HRS Type 2
Pathogenesis of HRS 2
Seminars in Liver Disease 2008;28: 81-95
HRS Type 2
• Less severe (creatinine1.5 mg/dL [132μM/L])
• More slowly progressive with a mean survival of 6 months.
• Usually appears spontaneously
• Associated with refractory ascites
Seminars in Liver Disease 2008;28: 81-95
Pathogenesis of HRS 1
Seminars in Liver Disease 2008;28: 81-95
HRS Type 1
• Rapid impairment of renal function– Serum creatinine level greater than 2.5 mg/dL
(>220 μM/L) within 2 weeks
• Frequently with precipitating factor– Infection, esp SBP– GI hemorrhage– Acute hepatitis
Seminars in Liver Disease 2008;28: 81-95
Survival
Gastroenterology 1993;271: 1121- 1125
Treatment -1
• Pharmacological Treatment– Renal vasodilator
• Dopamine, PGE1,E2,I2: all been tried without success
– Systemic (splanchnic) vasoconstrictor• Terlipressin• Midodrine• Norepinephrine
– Volume expander• albumin
Drug DosageDrug Dose Others
Terlipressin 0.5mg~1mg q4~6h If no early response, double dose qod. Max:
12mg/day
Midodrine& Octreotide
Midodrine 7.5~12.5mg po or iv tid+
Octrotide sc 100~200 μg tid
Adjust midodrine: to keep
MAP>90mmHg
Norepinephrine 0.5mg~3mg/hr
Albumin 1g/kg Day1, max: of 100g, then 20-40g/day
Duration: until reversal of HRS or for a maximum 14 days
National Taiwan University Hospital
Treatment -2
• TIPS(Transjugular intrahepatic portosystemic shunt)
• Liver transplantation
Pretransplant Renal Function
• Both duration and degree of renal impairment before LTx have been linked with incidence and progression of kidney dysfunction postoperatively
• Pretransplant renal function has remained an independent predictor of posttransplant mortality
HRS and LTx -1
• HRS is not always cured by orthotopic liver transplant– 28 patients(13 on dialysis) with type 1 HRS who
under went LTx in whom renal dysfunction resolved in 16(57%)
Nephrol Dial Transplant (2006) 21: 478–482
HRS and LTx -2
ARCH SURG/VOL 141, AUG 2006
ARCH SURG/VOL 141, AUG 2006
• American consesus conference suggested 6 weeks as a threshold after which LKTx should be considered
American Journal of Transplantation 2008; 8: 2243–2251
Spontaneous recovery of renal function after LTx -1
• United Network for Organ Sharing (UNOS) / Organ Procurement and Transplantation Network database
• February 27, 2002 and January 18, 2007
LIVER TRANSPLANTATION 16:440-446, 2010
Spontaneous recovery of renal function after LTx -2
LIVER TRANSPLANTATION 16:440-446, 2010
Spontaneous recovery of renal function after LTx -3
LIVER TRANSPLANTATION 16:440-446, 2010
LIVER TRANSPLANTATION 16:440-446, 2010
For Patients not on dialysis at the Time of OLT
• For patients with either AKI /HRS, SLK should not be considered based on – the absence of studies showing meaningful benefit
compared to OLT for this population– the potential for some reversibility to the acute
injury component data demonstrating a low likelihood of progressive CKD in the first few years after OLT.
For Patients on dialysis at the Time of OLT
• Patients who were on dialysis for less than 8 weeks should be listed for LTA based on – the absence of an established survival benefit for
SLK in patients before 8 weeks– data from University of California at Los Angeles
(UCLA) indicating that over 90% of patients dialyzed for HRS for less than or equal to 4 weeks will recover renal function after LTA
Renal Biopsy??
Transplantation, 2011
Discussion
1. Renal prognosis after liver transplantation for hepatorenal syndrome
2. Indication of simultaneous liver-kidney transplantation
Chronic Kidney Disease
• Secondary to glomerulonephritis, polycystic kidney disease, and primary hyperoxaluria
Transplantation • Volume 86, Number 11, December 15, 2008
Scientific Registry of Transplant Recipients (SRTR)/ Organ Procurement and Transplant Network(OPTN)
• 2002/2/27~2005/12/30
• At listing( 人 ) LTA SLK
Not on dialysis 27343 605
On dialysis 577 579
American Journal of Transplantation 2007; 7: 1702–1709
MELD At listing At transplant
LTA Not on dialysis 14 18
On dialysis 38 39
SLK Not on dialysis 25 26
On dialysis 31 31
American Journal of Transplantation 2007; 7: 1702–1709
Waitlist Survial
American Journal of Transplantation 2007; 7: 1702–1709
Posttransplant Survival
American Journal of Transplantation 2008; 8: 2243–2251
1
2 4
3
American Journal of Transplantation 2008; 8: 2243–2251
KALT & CLKT
• Organ Procurement and Transplant Network (OPTN)/United Network for Organ Sharing (UNOS)
• 1996/1~2003/12
• KALT: 352, CLKT: 1136
Transplantation • Volume 82, Number 10, November 27, 2006
Transplantation • Volume 82, Number 10, November 27, 2006
Transplantation • Volume 82, Number 10, November 27, 2006
Algorithm for SLK Candidate Evaluation
American Journal of Transplantation 2007; 7: 1702–1709 1705
Algorithm for SLK Candidate Evaluation
American Journal of Transplantation 2007; 7: 1702–1709 1705
Indications for LKTx(The Consensus Conference on Simultaneous Liver Kidney Transplantation Review Board)
• Endstage renal disease and symptomatic portal hypertension or hepatic vein wedge pressure gradient more than 10 mm Hg
• Liver failure and CKD with GFR less than 30 mL/min
• AKI or HRS with creatinine more than 2.0 mg/dL and on dialysis more than 8 weeks
• Liver failure and CKD with renal biopsy demonstrating more than 30% glomerulosclerosis 30% fibrosis
Nature Clinical Practice Nephrology (2007) 3, 507-514
CLKT in Pre-MELD and Post-MELD -1
Nature Clinical Practice Nephrology (2007) 3, 507-514
CLKT in Pre-MELD and Post-MELD -2
Nature Clinical Practice Nephrology (2007) 3, 507-514
NTUH ExperienceAge ICU
indicationLTX Total
dialysis date
林 O意 2645594 M 38 Liver failure O 41
林 O枝 4291460 F 32 Liver failure 3
蔡 O卿 4302503 F 40 Liver failure 5
蔡 O堂 3066964 M 5 LTX O 10
林 O淑瓊 4396578 F 67 Liver failure 5
簡 O鈴 4582287 M 50 LTX O 17
王 O鈞 5022759 M 26 Liver failure 25
徐 O華 2309920 F 50 LTX O 59
方 O珊 2138061 F 52 Liver failure O 7
曾 O珠 3901646 F 49 Liver failure O 58