Steroid Treatment for Alcoholic Hepatitis
Prednisolone 40 mg daily for 28 days is the standard corticosteroid regimen for severe alcoholic hepatitis. 1
Defining Severe Disease
Severe alcoholic hepatitis requiring steroid therapy is defined by any of the following criteria: 2, 1
- Maddrey Discriminant Function (mDF) score ≥32
- MELD score >21
- Glasgow Alcoholic Hepatitis Score (GAHS) ≥9
- Presence of hepatic encephalopathy
Treatment Protocol
Initial Therapy
Prednisolone (not prednisone) is the specific corticosteroid used because it is the active metabolite and does not require hepatic conversion. 2, 1 The standard regimen is:
- Prednisolone 40 mg orally daily for 28 days 2, 1
- This improves 28-day survival from 65.1% to 84.6% in patients with mDF ≥32 2
Monitoring Response at Day 7
Response to steroids must be assessed at day 7 using the Lille model score: 2, 1
- Complete responders (Lille score ≤0.16): 91.1% 28-day survival - continue full 28-day course 2, 1
- Partial responders (Lille score 0.16-0.56): 79.4% 28-day survival - continue full 28-day course 2, 1
- Null responders (Lille score ≥0.56): 53.3% 28-day survival - discontinue steroids immediately and consider liver transplantation 2, 1
The Lille score incorporates bilirubin change from day 0 to day 7 along with other variables, and a score ≥0.56 indicates futility of continued steroid therapy. 2
Absolute Contraindications to Steroids
Steroids are contraindicated in the following situations: 2, 1
- Active infection or sepsis
- Gastrointestinal bleeding
- Acute renal failure
- Acute pancreatitis
In these cases, pentoxifylline 400 mg three times daily for 28 days may be considered as an alternative, though it is less effective (74.5% vs 87.0% one-month survival compared to prednisolone). 2, 3
Important Safety Considerations
Serious infections occur in 13% of prednisolone-treated patients versus 7% of controls (p=0.002). 4, 5 Specifically, fungal infections are more common with steroid use (8 of 528 steroid-treated patients vs 1 of 534 controls). 6 However, corticosteroids do not increase bacterial infection rates or infection-related mortality. 6
What Does NOT Work
Pentoxifylline provides no survival benefit and should not be used as first-line therapy. 4, 5 The STOPAH trial definitively showed an odds ratio of 1.07 for 28-day mortality with pentoxifylline (95% CI 0.77-1.49, p=0.69), meaning it is ineffective. 5
Combination therapy with prednisolone plus pentoxifylline offers no additional benefit over prednisolone alone (4-week survival 72.2% vs 73.5%, p=1.00). 7
Critical Pitfall
The survival benefit of prednisolone is limited to 28 days only. 4, 5 At 90 days and 1 year, there are no significant differences in mortality between steroid-treated and untreated patients. 4, 5 Long-term survival depends entirely on achieving alcohol abstinence, which should be aggressively pursued in all patients. 1