What are the indications for liver transplantation?

Indications for Liver Transplantation

Liver transplantation is indicated for patients with end-stage liver disease causing life-threatening complications, acute liver failure, or hepatocellular carcinoma meeting specific criteria, with listing priority determined by MELD score ≥15 or standardized exception points for specific conditions. 1

Primary Disease Categories

Liver transplantation serves as definitive treatment across four major categories of liver disease:

Chronic Liver Disease (Cirrhosis)

• Chronic noncholestatic disorders including chronic hepatitis B/C, autoimmune hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis are established indications 1
• Cholestatic disorders including primary biliary cirrhosis, primary sclerosing cholangitis, and biliary atresia warrant transplantation 1
• Metabolic disorders such as alpha-1-antitrypsin deficiency, Wilson disease, and hemochromatosis causing cirrhosis are appropriate indications 1
• Referral should occur at the onset of any major complication (variceal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis) or significant coagulopathy, before development of malnutrition, hepatorenal failure, and advanced disease severity 1, 2

Acute Liver Failure

• All patients with non-paracetamol acute and subacute liver failure with encephalopathy (including fulminant Wilson's disease) must be referred to a transplant center immediately 3, 1
• For paracetamol hepatotoxicity, specific King's College criteria guide referral: arterial pH <7.3 after resuscitation, OR all three of: prothrombin time >100 seconds (INR >6.5), serum creatinine >300 μmol/L, and grade III-IV encephalopathy 3
• For non-paracetamol acute liver failure, refer if: non-A, non-B hepatitis etiology, age <10 or >40 years, jaundice to encephalopathy interval >7 days, prothrombin time >50 seconds, OR serum bilirubin >300 μmol/L 3
• Patients with progressive coagulopathy without encephalopathy warrant discussion with a transplant center 3, 1

Hepatocellular Carcinoma

• Small hepatocellular carcinoma complicating cirrhosis meeting Milan criteria (single lesion ≤5 cm or up to 3 lesions each ≤3 cm, no vascular invasion, no extrahepatic disease) provides 4-year survival of 75% with 83% recurrence-free survival 1
• Extrahepatic hepatocellular carcinoma is an absolute contraindication 1

Metabolic Disorders with Extrahepatic Manifestations

• Liver-based genetic defects triggering damage to other organs (e.g., familial amyloidosis, primary hyperoxaluria) are indications even when liver function is preserved 1, 2

MELD Score-Based Prioritization

The Model for End-stage Liver Disease (MELD) score determines allocation priority and identifies transplant benefit:

• MELD ≥15 represents the threshold for transplant listing, as transplant benefit exceeds waitlist mortality risk at this point 1, 2
• MELD >30 receives urgent priority with macro-area level allocation 1
• MELD 15-29 receives standard priority with regional allocation 1
• Maximal benefit occurs when expected survival on the waiting list is higher with than without transplantation 2

MELD Exception Categories

Standardized exception points are granted for conditions where MELD underestimates mortality risk:

• Hepatopulmonary syndrome 1
• Portopulmonary hypertension 1
• Refractory hydrothorax 1
• Late acute retransplantation 1
• Hepatocellular carcinoma meeting Milan criteria 1

Disease-Specific Considerations

Alcoholic Liver Disease

• Decompensated alcoholic cirrhosis with Child-Pugh class C or MELD-Na ≥21 requires referral for transplantation 1
• Patients failing to improve after 3 months of abstinence, particularly with Child-Pugh class C cirrhosis, should be referred 4
• A 6-month abstinence period is desirable but not mandatory; selection should not be based solely on fixed abstinence intervals but rather comprehensive evaluation of recidivism risk factors including duration of preoperative abstinence, denial of alcoholism, lack of familial/occupational support, antisocial behavior, and history of psychiatric disorders or drug abuse 1, 4, 5
• Liver allograft and recipient survival for alcoholic liver disease are among the highest of all indications, with 5-year survival approximately 65-80% 1, 5

Primary Biliary Cirrhosis

• Primary biliary cirrhosis is an excellent indication for transplantation with over 80% one-year patient survival 3
• Referral should occur once serum bilirubin exceeds 100 μmol/L or significant impairment of liver function ensues 3
• Earlier referral is justified if intractable pruritus, debilitating lethargy, or other complications are prominent 3

Primary Sclerosing Cholangitis

• Transplantation provides 89% five-year survival versus 31% with conservative management 3
• Cholangiocarcinoma complicating PSC is an absolute contraindication 1

Absolute Contraindications

The following conditions preclude liver transplantation:

• AIDS 1
• Extrahepatic malignancy (with rare exceptions for specific neuroendocrine tumors) 1
• Advanced cardiopulmonary disease 1
• Cholangiocarcinoma (except highly selected cases with neoadjuvant protocols) 1
• Limited life expectancy from non-liver-related comorbidities 1

Relative Contraindications

These conditions weigh heavily against transplantation but are not absolute:

• HIV positivity (controlled disease may be acceptable) 1
• Age above 70 years (acceptable with favorable comorbidity profile) 1, 6
• Significant active sepsis 1
• Active alcohol/substance misuse 1, 4
• Severe psychiatric disorder 1
• Portal venous system thrombosis 1
• Pulmonary hypertension 1
• Body mass index extremes (≥40 or <18.5) 6

Evaluation Requirements

Multidisciplinary assessment involving transplant hepatologist, transplant surgeon, and specialists (including addiction specialist for alcohol-related disease) is mandatory 1, 4

The evaluation must:

• Assess comorbidities compromising post-transplant outcomes 1
• Evaluate ability to comply with complex medical regimens 1
• Exclude significant comorbid disease 1, 4
• Include comprehensive psychosocial assessment by addiction specialist for alcohol-related disease 4
• Determine time of last alcohol use and predict likelihood of achieving abstinence (for alcoholic liver disease) 4

Critical Timing Considerations

• Early referral facilitates optimal timing and improves outcomes 1, 7
• Delays in referral allow unfavorable complications of advanced liver disease to supervene, jeopardizing outcomes 3
• The evaluation process itself takes time, so beginning evaluation does not mean immediate listing or transplantation 4
• For acute liver failure, early referral is crucial due to high mortality with medical therapy and unpredictable evolution 8, 2