What is the recommended steroid treatment for severe alcoholic hepatitis?

Steroid Treatment for Severe Alcoholic Hepatitis

Prednisolone 40 mg daily for 28 days is the recommended first-line treatment for severe alcoholic hepatitis, defined as having a Maddrey Discriminant Function (mDF) score ≥32 or hepatic encephalopathy. 1

Diagnosis and Assessment

• Severe alcoholic hepatitis requiring steroid treatment is defined by:

  • mDF score ≥32 1
  • MELD score >21 1
  • Glasgow Alcoholic Hepatitis Score (GAHS) ≥9 1
  • Presence of hepatic encephalopathy 1

• Patients with mild alcoholic hepatitis (mDF <32, MELD <18, GAHS <8) generally improve with abstinence and supportive care alone 1

First-Line Treatment

• Prednisolone 40 mg daily for 28 days is the standard treatment regimen for severe alcoholic hepatitis 1

• Methylprednisolone 32 mg daily is an acceptable alternative to prednisolone 1, 2

• Steroid therapy has been shown to improve short-term (28-day) survival in patients with severe alcoholic hepatitis 1, 2

Contraindications to Steroid Therapy

• Steroids are contraindicated in patients with: 1
  • Active infection or sepsis
  • Gastrointestinal bleeding
  • Acute renal failure
  • Acute pancreatitis

Monitoring Response to Treatment

• Early response to steroid treatment should be assessed at day 7 using: 1

  • Early Change in Bilirubin Level (ECBL): Bilirubin level at day 7 should be lower than day 1
  • Lille model score: Categorizes patients as:
    • Complete responders (score ≤0.16)
    • Partial responders (score 0.16-0.56)
    • Null responders (score ≥0.56)

• 28-day survival rates based on Lille score: 1

  • Complete responders: 91.1%
  • Partial responders: 79.4%
  • Null responders: 53.3%

Treatment Algorithm

1. For patients with mDF ≥32 without contraindications:

   • Start prednisolone 40 mg daily for 28 days 1
   • Assess response at day 7 using Lille model 1

2. If Lille score <0.56 (responder):

   • Continue prednisolone for full 28-day course 1
   • Consider tapering over 2 weeks after completion 1, 3

3. If Lille score ≥0.56 (null responder):

   • Discontinue steroids 1
   • Consider liver transplantation evaluation in appropriate candidates 1

4. For patients with contraindications to steroids:

   • Pentoxifylline 400 mg three times daily for 28 days can be considered as an alternative 1
   • However, recent evidence shows pentoxifylline is less effective than prednisolone 1, 4

Alternative Treatments

• Pentoxifylline:

  • Less effective than prednisolone but may be used when steroids are contraindicated 1
  • Primarily reduces mortality by decreasing hepatorenal syndrome 1
  • Recent guidelines state it "must no longer be offered to patients with severe alcoholic hepatitis because of its ineffectiveness" 1

• Combination therapy:

  • Combining prednisolone and pentoxifylline shows no survival benefit over prednisolone alone 1, 5, 6

• N-acetylcysteine with corticosteroids:

  • May improve short-term survival at 1 and 3 months 1
  • Not consistently recommended as confirmatory studies are needed 1

Common Pitfalls and Caveats

• Steroid therapy should not be delayed excessively; however, a systematic evaluation taking up to a week before initiation is reasonable to rule out contraindications 3

• Infections are a common complication of steroid therapy, occurring in 13% of treated patients versus 7% in untreated patients 4, 3

• Long-term outcomes depend primarily on achieving alcohol abstinence, which should be strongly recommended to all patients 1

• The 6-month survival rate is 82% in patients with confirmed ECBL but only 23% in those without ECBL 1

• Despite improving short-term survival, steroids have not consistently shown benefits in medium or long-term survival 1, 4