What is the recommended treatment for severe alcoholic hepatitis?

Treatment of Severe Alcoholic Hepatitis

For severe alcoholic hepatitis, prednisolone 40 mg daily for 28 days is the recommended first-line treatment for patients with Maddrey Discriminant Function (MDF) >32 or MELD score >20, with treatment response assessed at day 7 using the Lille model. 1

Disease Severity Assessment

• Severity should be determined using validated scoring systems:
  • Maddrey Discriminant Function (MDF) >32
  • MELD score >20 (optimal benefit with MELD 25-39) 2
  • Glasgow Alcoholic Hepatitis Score ≥9
  • ABIC score category C

First-Line Treatment

Corticosteroid Therapy

• Prednisolone 40 mg daily orally for 28 days for patients with severe alcoholic hepatitis 1, 3
• Response assessment at day 7 using:
  • Lille model (optimal cutoff: <0.45 indicates response)
  • Early Change in Bilirubin Level (ECBL)
• Response classification 3:
  • Complete responders (Lille ≤0.16): continue prednisolone
  • Partial responders (Lille 0.16-0.56): continue prednisolone
  • Null responders (Lille ≥0.56): discontinue steroids and consider liver transplantation

Contraindications to Corticosteroids

• Uncontrolled infection
• Gastrointestinal bleeding
• Renal failure
• Pancreatitis
• Hepatitis B viral infection
• Tuberculosis

Alternative Treatments

• N-acetylcysteine + corticosteroids can be considered as it shows short-term benefit 1
• Pentoxifylline is no longer recommended as an alternative to steroids due to ineffectiveness 1, 4
  • The STOPAH trial showed pentoxifylline did not improve survival 4
  • A randomized trial comparing pentoxifylline and prednisolone combination versus prednisolone alone showed no survival benefit 5

Emerging Therapies

• Fecal microbiota transplantation (FMT) has shown promise in recent research:
  • A 2023 randomized trial showed improved 90-day survival with FMT (75%) compared to prednisolone (56.6%) 6
  • FMT was associated with fewer infections (3.6% vs 19.3% with prednisolone) 6

Supportive Care

• Complete alcohol abstinence is critical for survival 1, 3
• Nutritional support:
  • Protein intake: 1.2-1.5 g/kg/day
  • Caloric intake: 35-40 kcal/kg/day
  • Consider enteral feeding if patient cannot eat 3
• Vitamin and mineral supplementation (vitamin A, thiamine, B12, folate, pyridoxine, vitamin D, zinc) 1
• Infection screening before initiating corticosteroids:
  • Blood cultures
  • Urine cultures
  • Ascites fluid cultures if present 1

Liver Transplantation

• Consider early liver transplantation for carefully selected patients who:
  • Fail medical therapy (Lille score ≥0.56)
  • Have MELD score >26
  • Have good insight into their alcohol use disorder
  • Have good social support 3, 1

Monitoring and Complications

• Avoid nephrotoxic drugs, including diuretics 3
• Monitor for development of infections, which increase mortality risk 1
• Watch for hepatorenal syndrome, an early manifestation of multi-organ failure 3

Important Caveats

• The benefit of corticosteroids is modest and limited to 28 days, with no improvement in long-term survival 3
• Patients with MELD >51 do not benefit from corticosteroids 2
• Infection risk is significantly higher with prednisolone (13%) compared to no prednisolone (7%) 4
• Long-term outcomes depend primarily on maintaining abstinence from alcohol 1