combine conference 2011.05.18 r4 李思穎 / vs 賴俊夫. a 48-year-old woman with vomiting with...

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