Transplantation in Alcoholic Hepatitis: What We Have Learned

Transplantation in Alcoholic Hepatitis: What We Have Learned

Lecture Summary — Thomas Cotter, MD

1. Main Clinical Topics Discussed

• Pathogenesis, diagnosis, and prognostic scoring of alcohol-associated hepatitis (AH)
• Pharmacotherapeutic management of severe AH (steroids and emerging alternatives)
• Alcohol use disorder (AUD): epidemiology, DSM-5 criteria, and pharmacotherapy
• Early liver transplantation (ELT) as a management option in refractory severe AH

2. Key Learning Points, Guidelines, and Recommendations

Diagnosis of AH (AASLD Definition):

• Recent jaundice + regular alcohol consumption + compatible biochemical abnormalities, in the absence of clear confounders
• Liver biopsy not required for probable AH in clinical practice
• However, biopsy should be considered when diagnosis is uncertain — a Newcastle (UK) study found 25% of clinically suspected AH cases were actually advanced decompensated alcohol-associated cirrhosis on biopsy, representing significant misclassification

Severity Classification:

• Severe AH defined by:

- Maddrey's Discriminant Function (MDF) ≥ 32

- MELD score ≥ 21

• Prognostic tools include: MDF, MELD, ABIC score (Spain), GAHS (UK, limited external validation), and the Lille score (assessed days 4–7 post-steroid initiation)

Historical note on MDF: Creatinine was intentionally excluded from the original MDF in the 1970s (Johns Hopkins) due to concerns about falsely inflating scores in isolated renal failure; creatinine was later incorporated into the MELD score developed at Mayo Clinic

Steroid Management:

• Prednisolone remains the standard of care for eligible patients with severe AH
• Contraindications to steroids:

- Uncontrolled infection

- AKI with creatinine > 2.5

- Uncontrolled upper GI bleeding

• GI bleeding is NOT a contraindication once hemostasis is achieved — retrospective data show no survival difference
• Infection should be treated, not used to withhold steroids — treated infection does not negate steroid benefit
• The 28-day steroid duration is arbitrary, derived from 1970s NIH funding logistics; emerging data suggest 7 days may be sufficient
• "Fast fallers" (>20% bilirubin reduction by day 7) may not require steroid treatment — improved 90-day survival with abstinence alone

AUD Pharmacotherapy:

• Acamprosate: renally excreted — preferred in advanced liver disease
• Naltrexone: IM formulation useful for compliance; use with caution in liver disease (hepatic metabolism)
• Baclofen: only AUD agent studied in advanced liver disease; not FDA-approved; requires dose titration
• Gabapentin (off-label): renally excreted; useful if insomnia or neuropathy present
• Supervised detoxification and benzodiazepine taper should be considered before initiating AUD medications in actively drinking patients

3. Specific Clinical Data, Statistics, and Study Results