General Framework: Why Transplant?
Liver transplantation is indicated when (1) liver disease is expected to cause death or severe morbidity without transplant, (2) liver disease is not likely to recur or progress fatally after transplant, and (3) the patient has a reasonable chance of surviving the transplant surgery and achieving acceptable long-term outcomes. These three principles underpin every listing decision.
Major Indications
1. Decompensated Chronic Liver Disease
The most common indication. Decompensation is defined by the development of:
- Ascites (especially refractory ascites requiring repeated paracentesis)
- Spontaneous bacterial peritonitis
- Variceal hemorrhage
- Hepatic encephalopathy
- Hepatorenal syndrome
MELD 3.0 ≥15 is generally considered the threshold at which survival benefit from transplantation outweighs operative risk. Below MELD 15, the risk of surgery may exceed the risk of continued medical management.
Common underlying etiologies: alcohol-related liver disease, MASLD/MASH, chronic HBV, chronic HCV (now largely curable with DAAs — transplant indication declining), autoimmune hepatitis, PBC, PSC.
2. Acute Liver Failure (ALF)
ALF is defined as hepatic encephalopathy and coagulopathy (INR ≥1.5) within 26 weeks of onset of liver disease in a patient without prior chronic liver disease. It carries a mortality of >80% without transplantation.
Causes: Acetaminophen toxicity (most common in US — can recover with NAC if caught early), viral hepatitis (HAV, HBV), drug-induced liver injury, Wilson's disease, autoimmune hepatitis, Budd-Chiari, indeterminate.
King's College Criteria: Used to identify which ALF patients are unlikely to survive without transplant. Acetaminophen criteria: pH <7.30 OR (PT >100s AND creatinine >3.4 AND Grade III-IV HE). Non-acetaminophen criteria: PT >100s OR any 3 of [age <10 or >40, DILI or Wilson's, jaundice >7 days before HE, bilirubin >17.5, PT >50s].
ALF patients are listed as Status 1A — the highest priority in UNOS allocation, bypassing MELD-based scoring entirely.
3. Hepatocellular Carcinoma (HCC)
HCC arising in cirrhotic livers is a major indication for transplantation. Transplant offers the dual benefit of treating the cancer and the underlying cirrhosis.
Milan Criteria (standard): 1 lesion ≤5 cm OR 2–3 lesions each ≤3 cm, no vascular invasion, no extrahepatic spread. Patients within Milan criteria receive MELD exception points — an upward adjustment to their MELD score to compensate for the fact that HCC itself does not raise creatinine, bilirubin, or INR.
UCSF Criteria: Expanded criteria (1 lesion ≤6.5 cm OR 2–3 lesions ≤4.5 cm each and total tumor diameter ≤8 cm) adopted by some centers with comparable outcomes.
Bridging therapy (TACE, ablation) is often used to prevent tumor progression while awaiting transplant.
4. Cholestatic Liver Diseases
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) can progress to cirrhosis requiring transplantation. PSC also carries significant risk of cholangiocarcinoma — a contraindication to transplant in most cases.
5. Metabolic Liver Diseases
Wilson's disease (presenting as ALF — Status 1A), hereditary hemochromatosis (advanced cirrhosis), alpha-1 antitrypsin deficiency, and others may require transplantation.
Key Contraindications
Absolute: Active extrahepatic malignancy, active untreated infection outside the biliary tree, active alcohol or drug use (variable by program — typically require documented abstinence period), severe cardiopulmonary disease precluding surgery, anatomic precluding transplant, cholangiocarcinoma (most cases).
Relative: Age >70, severe obesity (BMI >40), prior complex abdominal surgery, multi-organ dysfunction — evaluated case by case.
The Evaluation Process
Transplant evaluation is multidisciplinary and typically involves:
- Hepatology: confirm indication, optimize medical management, calculate MELD
- Transplant surgery: assess operative candidacy and anatomy
- Cardiology: cardiac risk stratification (echo, stress test, right heart cath)
- Pulmonology: exclude hepatopulmonary syndrome, portopulmonary hypertension
- Nephrology: assess baseline renal function
- Psychiatry / social work: assess psychosocial support, substance use history, adherence capacity
- Financial counselor: insurance and compliance verification
- Infectious disease: vaccination review, latent TB screening