Prednisolone Schedule for Alcoholic Hepatitis
For patients with severe alcoholic hepatitis (defined by Maddrey Discriminant Function score ≥32), prednisolone should be administered at 40 mg daily for 28 days, followed by either discontinuation or a 2-week taper depending on clinical response. 1
Assessment of Severity
Before initiating prednisolone, determine the severity of alcoholic hepatitis:
- Severe alcoholic hepatitis: Maddrey Discriminant Function (MDF) score ≥32 or presence of hepatic encephalopathy
- Mild-moderate alcoholic hepatitis: MDF score <32, no hepatic encephalopathy
Calculation of MDF:
- MDF = 4.6 × [patient's prothrombin time - control prothrombin time (seconds)] + serum bilirubin (mg/dL)
Treatment Algorithm
Step 1: Evaluate for contraindications to steroid therapy
- Active infection
- Gastrointestinal bleeding
- Renal failure
- Active pancreatitis
Step 2: Initiate treatment based on severity and contraindications
For severe alcoholic hepatitis WITHOUT contraindications:
- Prednisolone 40 mg orally daily for 28 days 1
- After 28 days: either discontinue or taper over 2 weeks 1
For severe alcoholic hepatitis WITH contraindications:
- Consider pentoxifylline 400 mg orally three times daily for 28 days 1
- Note: Recent evidence suggests pentoxifylline is no longer recommended due to ineffectiveness 1, 2
For mild-moderate alcoholic hepatitis:
- Supportive care and abstinence only
- No steroid therapy needed 1
Step 3: Assess response at day 7
Use the Lille model to assess early response to steroid therapy:
- Complete responders (Lille score ≤0.16): Continue prednisolone for full 28 days
- Partial responders (Lille score 0.16-0.56): Continue prednisolone for full 28 days
- Null responders (Lille score ≥0.56): Consider discontinuing steroids and evaluating for liver transplantation 1
Emerging Evidence on Dosing Regimens
Recent research suggests that a tapered prednisolone regimen (starting at 40 mg/day and tapering by 10 mg/day weekly over 4 weeks) may reduce the frequency of infections compared to the standard fixed dose of 40 mg/day for 4 weeks 3. This approach resulted in significantly lower infection rates (19.7% vs 33.1%) by day 90, particularly for microbiologically proven infections (8.6% vs 19%).
Combination Therapies
- Prednisolone + N-acetylcysteine: May improve 1-month survival but does not improve 6-month survival 4. Consider in selected cases with weak evidence supporting its use 1.
- Prednisolone + pentoxifylline: Not recommended as it shows no survival benefit over prednisolone alone 2, 5.
Monitoring During Treatment
- Week 1: Assess early response using the Lille model
- Daily: Monitor for signs of infection (fever, leukocytosis)
- Weekly: Check liver function tests, renal function, and blood glucose
- Throughout treatment: Screen for complications of steroid therapy (hyperglycemia, infections)
Common Pitfalls to Avoid
- Failure to calculate MDF score: This may lead to inappropriate treatment of patients with mild disease or missed treatment opportunities for severe cases
- Missing early treatment failure: Not assessing Lille score at day 7 may result in continued ineffective therapy
- Overlooking infections: Steroids increase infection risk; perform thorough infection screening before and during treatment
- Inappropriate continuation: Continuing steroids beyond 28 days without tapering increases risk of complications without additional benefit
Long-term Management
The cornerstone of long-term management is complete alcohol abstinence, which must be strictly recommended as continued alcohol use is associated with disease progression 1, 6. Consider naltrexone or acamprosate in combination with counseling to decrease the likelihood of relapse in patients who achieve abstinence 1.
Remember that while prednisolone improves short-term survival, it has not been shown to improve medium or long-term survival 1, highlighting the critical importance of addressing the underlying alcohol use disorder.