What are the indications for liver transplantation?

Liver Transplant Indications

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

Primary Disease Categories

Chronic Liver Disease

• Chronic noncholestatic disorders: chronic hepatitis B/C, autoimmune hepatitis, and alcoholic liver disease are established indications 1
• Cholestatic disorders: primary biliary cirrhosis, primary sclerosing cholangitis, and biliary atresia warrant transplantation 1
• Metabolic disorders: alpha-1-antitrypsin deficiency, Wilson disease, and nonalcoholic steatohepatitis causing cirrhosis are appropriate indications 1
• Referral should occur before development of malnutrition, hepatorenal failure, and advanced disease severity to optimize outcomes 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 2
• Patients with paracetamol hepatotoxicity meeting specific criteria require specialist center referral 2
• Progressive coagulopathy without encephalopathy warrants discussion with a transplant center 2

MELD Score-Based Prioritization

Listing Criteria

• MELD score ≥15 represents the threshold for transplant listing, as transplant benefit exceeds waitlist mortality risk at this point 1
• MELD >30 receives urgent priority with macro-area level allocation 1
• MELD 15-29 receives standard priority with regional allocation 1

Disease-Specific Indications

Hepatocellular Carcinoma

• Small HCC complicating cirrhosis meeting Milan criteria (single tumor ≤5 cm or up to 3 tumors ≤3 cm without vascular invasion) is recommended for transplantation 2, 1
• This provides 4-year survival of 75% with 83% recurrence-free survival 1
• Tumors >5 cm or >3 in number should only be assessed with novel management strategies 2
• Extrahepatic HCC disease (local or systemic) is an absolute contraindication 2, 1
• Fibrolamellar variant is not constrained by standard size criteria 2

Alcoholic Liver Disease

• Transplantation in selected patients with advanced alcoholic liver disease improves outcomes 2, 1
• Decompensated alcoholic cirrhosis with Child-Pugh class C or MELD-Na ≥21 should be referred for transplantation 3
• Patients failing to improve after 3 months of abstinence, particularly with Child-Pugh C cirrhosis, require referral 3
• 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 2, 3
• Multidisciplinary psychosocial assessment including addiction specialist evaluation is essential 2, 3
• Alcohol dependence must be differentiated from non-dependent misuse 2
• Young patients with life-threatening presentation may not require usual stringent evaluation 2

Hepatitis B

• Patients with end-stage HBV-related disease must be HBV DNA negative before transplantation 2, 1
• Most HBV DNA positive patients can be rendered negative with antiviral treatment and should not be excluded from assessment 2
• Long-term hepatitis B immunoglobulin is effective for preventing reinfection 2
• Precore mutant HBV or HDV co-infection are not contraindications 2

Autoimmune Hepatitis

• Transplantation is viable for autoimmune hepatitis 2
• Indications include failure to achieve biochemical remission, shrinking liver volume, severe acute presentation, and progressive decompensation 2

Other Conditions

• Wilson's disease is a good indication for transplantation 2, 1
• Budd-Chiari syndrome requires management at centers offering decompressive surgery, transplantation, TIPS, and radiological intervention 2
• Genetic hemochromatosis is viable but considered higher risk than other elective indications 2
• Neuroendocrine tumors are the only metastatic liver tumors suitable for transplantation, but extrahepatic metastatic disease is a contraindication 2
• Epithelioid hemangioendothelioma requires expert histopathological review to exclude angiosarcoma; extrahepatic disease may not be a contraindication 2

Absolute Contraindications

The following conditions preclude transplantation: 2

• AIDS
• Extrahepatic malignancy (except hemangioendothelioma and neuroendocrine tumors in select centers)
• Advanced cardiopulmonary disease
• Cholangiocarcinoma (unless part of novel management strategy) 2, 1
• Limited life expectancy from non-liver-related comorbidities 1

Relative Contraindications

These conditions weigh heavily against transplantation but are not absolute: 2

• HIV positivity (not AIDS)
• Age above 70 years (though age >60 should not discourage transplantation) 2
• Significant sepsis outside extrahepatic biliary tree
• Active alcohol/substance misuse
• Severe psychiatric disorder
• Portal venous system thrombosis (requires transplant center assessment)
• Pulmonary hypertension (requires transplant center assessment)

MELD Exception Categories

Standardized exception points are granted for: 1

• Hepatopulmonary syndrome
• Portopulmonary hypertension
• Refractory hydrothorax
• Late acute retransplantation (receives priority 1 with 30 points, macro-area allocation)

Evaluation Requirements

• Multidisciplinary assessment involving transplant hepatologist, transplant surgeon, and specialists is mandatory 1
• Assessment must evaluate comorbidities compromising post-transplant outcomes, ability to comply with complex medical regimens, and exclude significant comorbid disease 2, 1
• Early referral facilitates optimal timing and improves outcomes 2

Common Pitfalls

• Active alcohol/substance misuse is a relative, not absolute, contraindication—emphasis is on "active" use rather than arbitrary time thresholds 2
• The 6-month abstinence rule alone is inadequate for predicting post-transplant drinking; comprehensive psychosocial evaluation is more predictive 3
• Strict application of the 6-month rule may unfairly penalize low-risk patients unlikely to survive the waiting period 3
• HBV DNA positivity is a relative contraindication since most patients can be treated successfully 2