What are the indications and considerations for a liver transplant in an adult patient with a history of liver disease, such as cirrhosis or liver cancer, who has not responded to previous treatments?

Liver Transplantation: Indications and Considerations

Liver transplantation should be considered for any adult patient with end-stage liver disease when expected survival without transplant is one year or less, when major complications of cirrhosis develop (variceal hemorrhage, ascites, hepatorenal syndrome, encephalopathy), when hepatocellular carcinoma meets Milan criteria, or in cases of acute liver failure. 1

Primary Indications for Liver Transplantation

End-Stage Liver Disease (Cirrhosis)

• Refer patients to transplant centers immediately when major complications occur, including variceal hemorrhage, ascites, hepatorenal syndrome, or encephalopathy. 1
• List patients for transplantation when MELD score reaches ≥15, as this represents the threshold where transplant benefit exceeds waitlist mortality risk. 2, 3
• Patients with MELD >30 receive urgent priority with macro-area level allocation. 2, 3
• Common etiologies include chronic hepatitis B/C, autoimmune hepatitis, alcoholic liver disease, primary biliary cirrhosis, primary sclerosing cholangitis, and metabolic disorders (alpha-1-antitrypsin deficiency, Wilson disease, nonalcoholic steatohepatitis). 2, 3

Acute Liver Failure

• All patients with non-acetaminophen acute liver failure with encephalopathy must be referred immediately to a transplant center. 2
• This represents an urgent indication with dramatically improved survival: from 10-20% without transplant to 75-80% at 1 year and 70% at 5 years post-transplant. 1
• Common causes include hepatitis viruses A and B, drugs (acetaminophen), toxic agents, and seronegative hepatitis. 1
• For acetaminophen overdose, transplant evaluation is necessary when arterial pH <7.30 OR when prothrombin time >100 seconds combined with serum creatinine >300 μmol/L and grade III-IV hepatic encephalopathy (King's College Criteria). 4

Hepatocellular Carcinoma (HCC)

• Transplantation is recommended for small HCC complicating cirrhosis meeting Milan criteria: single tumor ≤5 cm OR up to 3 tumors each ≤3 cm without vascular invasion. 1, 2, 3
• This achieves 4-year survival of 75% with 83% recurrence-free survival. 2, 3
• Tumors >5 cm or greater than three in number should only be assessed in conjunction with novel management strategies. 1
• Local or systemic extrahepatic HCC disease is an absolute contraindication. 1, 2, 3

Alcoholic Liver Disease

• Transplantation in selected patients with advanced alcoholic liver disease improves outcomes. 1, 2
• Decompensated alcoholic cirrhosis with Child-Pugh class C or MELD-Na ≥21 requires referral for transplantation. 2
• A 6-month abstinence period is desirable but not mandatory; selection should be based on comprehensive evaluation of recidivism risk factors rather than fixed abstinence intervals. 1, 2
• Psychosocial assessment by a multidisciplinary transplant team is required, differentiating alcohol dependence from non-dependent misuse. 1

Viral Hepatitis

Hepatitis B:

• Patients must be HBV DNA negative before transplantation (based on commercial non-PCR assays). 1, 3
• Most HBV DNA positive patients can be rendered negative with antiviral treatment and should not be excluded from assessment. 1, 3
• Long-term passive immunization with hepatitis B immunoglobulin is effective in preventing reinfection. 1
• Precore mutant HBV or hepatitis D virus co-infection are not contraindications. 1

Hepatitis C:

• Patients with end-stage hepatitis C cirrhosis should be considered for transplantation. 1
• Genotype and viral load should not influence transplant assessment. 1
• On-going drug dependency is a relative contraindication. 1

Recurrent or Persistent Hepatic Encephalopathy

• Patients with end-stage liver disease and recurrent or persistent hepatic encephalopathy not responding to other treatments should be assessed for liver transplantation. 1
• Consider transplantation when MELD score is above 15 after an index complication including hepatic encephalopathy, or with history of recurrent hospitalization for overt hepatic encephalopathy. 1

Other Indications

• Wilson's disease is a good indication for transplantation, particularly with fulminant presentation, hemolysis, and renal failure. 1, 3
• Budd-Chiari syndrome: indicated for severe acute presentation, decompensated cirrhosis, failed shunt surgery, or caval compression. 1
• Neuroendocrine tumors are the only metastatic liver tumors suitable for transplantation for palliation (extrahepatic disease is contraindication). 1
• Epithelioid hemangioendothelioma: 5-year survival of 43-76% despite extensive disease; requires expert histopathological review to exclude angiosarcoma. 1

Absolute Contraindications

The following conditions preclude liver transplantation: 2, 3

• AIDS
• Extrahepatic malignancy
• Advanced cardiopulmonary disease
• Cholangiocarcinoma (unless in conjunction with novel management strategy) 1
• Limited life expectancy from non-liver-related comorbidities

Relative Contraindications

The following weigh heavily against transplantation but are not absolute: 2

• HIV positivity
• Age above 70 years
• Significant sepsis
• Active alcohol/substance misuse
• Severe psychiatric disorder
• Portal venous system thrombosis
• Pulmonary hypertension

MELD Exception Categories

Standardized exception points are granted for: 2, 3

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

Evaluation Requirements

• Multidisciplinary assessment involving transplant hepatologist, transplant surgeon, and specialists is mandatory. 2, 3
• Assessment must evaluate comorbidities compromising post-transplant outcomes and ability to comply with complex medical regimens. 1, 2, 3
• Referral should occur before development of malnutrition, hepatorenal failure, and advanced disease severity to optimize outcomes. 2
• Early referral facilitates optimal timing even before meeting full transplant criteria. 2, 4

Critical Timing Considerations

Common pitfall: Delaying referral until patients are too sick. Patients should be discussed with transplant centers as soon as progressive coagulopathy develops, even without encephalopathy. 4

Current 1-year survival after liver transplantation is 96%, with 10-year survival of 71%, representing dramatic improvement from historical outcomes. 1