Liver Transplantation Conference 경희대학교 병원 간이식팀 R3 최인승 /Prof. 김병호

Contents 1.Liver transplantation (LT) indications 2.Liver transplantation (LT) contra-indications 3.Timing of Liver transplantation (LT) 4.Post –transplant complications  Post-transplant infections 5.Patient cases.

Liver plantation (LT) indications Table Indications for Liver Transplantation Adult Chronic viral hepatitis Alcoholic cirrhosis Chronic viral hepatitis Fulminant hepatitis Primary hepatocellular malignancies Primary biliary cirrhosis Secondary biliary cirrhosis Primary sclerosing cholangitis Autoimmune hepatitis Caroli's disease c Cryptogenic cirrhosis Chronic hepatitis with cirrhosis Hepatic vein thrombosis Hepatic adenomas Nonalcoholic steatohepatitis Familial amyloid polyneuropathy Harrison’s Principles of internal medicine, 18e, ch 310.

Liver plantation (LT) indications Table Indications for Liver Transplantation Chronic noncholestatic liver disorders Chronic hepatitis C Chronic hepatitis B Autoimmune hepatitis Alcoholic liver disease Cholestatic liver disorders Primary biliary cirrhosis Primary sclerosing cholangitis Biliary atresia Nonsyndromic paucity of the intrahepatic bile ducts Cystic fibrosis Progressive familial intrahepatic cholestasis Fulminant hepatic failure Miscellaneous conditions Budd-Chiari syndrome Metastatic neuroendocrine tumors Polycystic disease Re-transplantation Metabolic disorders causing cirrhosis Alpha-1-antitrypsin deficiency Wilson disease Nonalcoholic steatohepatitis and cryptogenic cirrhosis Hereditary hemochromatosis Tyrosinemia Glycogen storage disease type IV Neonatal hemochromatosis Metabolic disorders causing severe extrahepatic morbidity Amyloidosis Hyperoxaluria, Urea cycle defects Disorders of branch chain amino acids Primary malignancies of the liver Hepatocellular carcinoma Hepatoblastoma Fibrolamellar hepatocellular carcinoma Hemangioendothelioma AASLD Practice Guidelines: Evaluation of the Patient for LT, Hepatology,2005

Liver plantation contra-indications Table Contraindications to Liver Transplantation Absoluterelative Uncontrolled extra-hepatobiliary infectionAge >70 Active, untreated sepsisPrior extensive hepatobiliary surgery Uncorrectable, life-limiting congenital anomal ies Portal vein thrombosis Active substance or alcohol abuseRenal failure not attributable to liver dise ase Advanced cardio-pulmonary diseasePrevious extrahepatic malignancy (not in cluding nonmelanoma skin cancer) Extrahepatobiliary malignancy (not including nonmelanoma skin cancer) Severe obesity Harrison’s Principles of internal medicine, 18e, ch 310.

When Should Evaluation for Transplantation Be Considered? Recommendations 1.Patients with cirrhosis should be referred for transplantation when they develop evidence of hepatic dysfunction (CTP > 7 and MELD > 10) or when they experience their first major complication (ascites, variceal bleeding, or hepatic encephalopathy) (II-3). 2. Children with chronic liver disease should be referred when they deviate from normal growth curves or develop evidence of hepatic dysfunction or portal hypertension (II-3). 3. Patients with type I hepato-renal syndrome should have an expedited referral for liver transplantation (II-3).

De-compensated liver cirrhosis 수술 후 1 년 생존률 ↔ 비수술 후 1 년 생존률 간이식후 1 년 사망률 : 10~15% 1 년 생존률이 90% 미만인 경우 대상이 됨 Child Pugh score ≥7 (B), MELD score ≥ 15

Fulminant hepatitis Criteria of King’s college Acetaminophen patient pH 6.5 (INR) and serum Cr > 3.4 mg/dL Non-acetaminophen patients PT > 6.5 (INR), or Any three of the following variables: Age 40 years Serum Bilirubin > 17.5 mg/dL Coagulation: PT > 3.5 (INR) Duration of jaundice before encephalopathy > 7 days Etiology: non-A, non-B hepatitis; halothane hepatitis; idiosyncratic drug reaction Gastroenterology 1989;97:439

Fulminant hepatitis Criteria of Hospital Paul-Brousse, Villejuif Factor V level < 20% in patient younger than 30 yrs of age, or < 30% in patient 30 yrs of age or older Hepatology 1991;14:49A

Hepatocellular carcinoma Milan 척도 – 단일 5 cm 이하 – 3 개 이하 최대 3 cm 이하 Milan Criteria (1996) a single HCC 3 cm without vascular invasion, regional node involvement, or distant metastases UCSF(University of California San Francisco) Criteria (2002) a solitary HCC < 6.5 cm or with up to three lesions, the largest of which was <4.5 cm with the sum of the diameters no larger than 8 cm

Timing of liver transplantation 뇌사자간이식 – 수요와 공급의 불균형 – Efficacy  Justice – 응급도와 대기시간 생체부분간이식 – 시기 결정이 더 자유롭다 – 이식이 결정되면 가능한 조기에 수술을 시행해야

국립 장기이식센터 응급도 분류 Status 1 Status 2A Status 2B Status 3 Status 7

Status 1 응급도 1

Status 2A 응급도 1

Status 2B 응급도 2

Status 3 & 7

Hepatology Volume 2011, page 9

Post-transplant complication (1) Table Nonhepatic Complications of Liver Transplantation Cardiovascular instability Arrhythmias, CHF, Cardiomyopathy Pulmonary compromisePneumonia Pulmonary capillary vascular permeability Fluid overload Renal dysfunctionPrerenal azotemia Hypoperfusion injury (acute tubular necrosis) Drug nephrotoxicity HematologicAnemia 2° to GI and/or intraabdominal bleeding Hemolytic anemia, aplastic anemia Thrombocytopenia InfectionBacterial: early, common postoperative infections Fungal/parasitic: late, opportunistic infections Viral: late, opportunistic infections, recurrent hepatitis NeuropsychiatricSeizures, metabolic encephalopathy Depression, difficult psychosocial adjustment Diseases of donorInfectious Malignant MalignancyB cell lymphoma (post-transplantation lympho-proliferative disorders) De novo neoplasms (particularly squamous cell skin carcinoma)

Post-transplant complication (2) Table Hepatic Complications of Liver Transplantation Hepatic Dysfunction Common after Major Surgery PrehepaticPigment load Hemolysis Blood collections (hematomas, abdominal collections) Intrahepatic EarlyHepatotoxic drugs and anesthesia Hypoperfusion (hypotension, shock, sepsis) Benign postoperative cholestasis LateTransfusion-associated hepatitis Exacerbation of primary hepatic disease PosthepaticBiliary obstruction decreased renal clearance of conjugated bilirubin Hepatic Dysfunction Unique to Liver Transplantation Primary graft nonfunction Vascular compromise (Portal vein obstruction, hepatic artery thrombosis, anastomotic leak with intraabdominal bleeding) Bile duct disorder (Stenosis, obstruction, leak) Rejection Recurrent primary hepatic disease

Post-transplant infections

Liver transplantation, 19;3~26, 2013

History Case 김 O F/75 DM (-), HTN (-) C-viral LC(Child C(10), MELD 26) Op Hx (-) Alcohol Hx (-) Smoking Hx (-)  73/F Hypothyroidism, Osteoporosis 로 본원 IE(pf. 우정택 ), C-viral LC(child C 10, MELD 26), HCC(LCSGJ stage II, T2N0M0, JIS 1) s/p TACE( ) #8( ) s/p Tomotherapy(2013.6) 로 본원 IG(pf. 김병호 ) f/u 하는 자로 ~26 까지 uncontrolled ascite 로 입원치료한 병력 있으며 이후 jaundice 악화되어 재 입원함. 환자 hepatic failure 로 L.T 고려 중임

Underlying liver function and performance status CBC/DC (‘ ) WBC(mm 3 )7270 Hb(g/dl)8.8 PLT(mm 3 ) 129,000 PT(sec)22.2 INR1.97 Performance status: Grade 0 Chemistry(‘ ) TB/DB(mg/dL)14.34/10.71 AST/ALT(IU/L)274/39 ALP/rGT(IU/L)220/303 Prot/Alb(g/dL)7.0/2.9 BUN/Cr(mg/dL)36/1.1 LC & Stage Child-PughC (10) MELD score 26 Esophageal varices(-) Ascites+ Encephalopathy± 김 O F/75 Case 1 Tumor markers AFP (ng/mL)54850 CEA (ng/mL) 7.14 PIVKA II (mAU/mL)2998 CA19-9 (U/mL) - Viral markers/ underlying liver disease HBV / HCV(-/+) HBeAg / HBeAb(-/-) Virus titer258,000 Antiviral Tx- Alcohol-

조 O 복 F/57 Case 1 Clinical Course 김 O F/75 Liver MR( ) Increased size of multiple HCCs. Aggravation of tumor thrombosis, extending the main portal vein. Large amount of ascites. ’09.7’13.3‘13.6’15.10 AFP PIVKA II Chronic hepatitis C Chronic hepatitis C S4 HCC TACE #1 S4 HCC TACE #1 Recur at S4/8 TACE #8 Recur at S4/8 TACE #8 Viable HCC S4/8 Tomotherapy Viable HCC S4/8 Tomotherapy Uncontrolled ascite

Summary 김 O F/75 Case 1 Current liver function Normal Well preserved (no risk of decompensation) Compensated (risk of decompensation) Decompensated Terminal state Extent of current tumor Localized (curative) Locally advanced (resectable) Locally advanced (unresectable) No < 4 Diffuse or multiple (> 3) Initial Tumor stage Date: 2012 년 4 월 Modified UICC ( 대한간암연구학회 ) T 2 N 0 M 0 Stage II JIS score 1 BCLC Very early / Early / Intermediate / Advanced / Terminal Current status Multiple HCC with decopmpensated liver function Risk factors of recurrence / Tumor biology Extrahepatic metastasis N Tumor size > 5 cm, capsulation N Tumor number 2 Repeated TACE ( 1 회 / 기간 ) 8 Vascular or bile duct invasion Y High uptake of PET N High AFP or PIVKA II Y Not normalized AFP after curative Tx Histology (microvascular invasion) - Histology (satellite lesion, differentiation) - Poor control of underlying liver disease -

Final diagnosis #1. HCC(T2N0M0, stage II, JIS score 3) s/p TACE #8(’13.3) s/p Tomotherapy(‘13.6) #2. C-viral LC c ascite(C, 10, MELD 26) #3. Hypothyroidism #4. Osteoporosis

Status 2A 응급도 1

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