Recommended Glucocorticoid for Alcoholic Hepatitis
Prednisolone 40 mg daily for 28 days is the recommended glucocorticoid for severe alcoholic hepatitis, as it is the standard treatment regimen endorsed by major gastroenterology and hepatology societies. 1
Why Prednisolone Specifically
- Prednisolone is the preferred formulation because it is the active metabolite and does not require hepatic conversion, making it superior to prednisone in patients with severe liver dysfunction 1
- The American College of Gastroenterology explicitly recommends prednisolone (not prednisone or other glucocorticoids) at 40 mg daily for 28 days as the standard regimen 1
- This improves short-term (28-day) survival by reducing pro-inflammatory cytokines including TNF-α 2
When to Use Prednisolone
Prednisolone should be initiated in patients meeting criteria for severe alcoholic hepatitis:
- Maddrey Discriminant Function (mDF) ≥32, OR 1
- MELD score >20-21, OR 1, 2
- Glasgow Alcoholic Hepatitis Score (GAHS) ≥9, OR 1
- Presence of hepatic encephalopathy regardless of other scores 2
Patients with mild disease (mDF <32, MELD <18, GAHS <8) do not require glucocorticoids and generally improve with abstinence and supportive care alone 1
Absolute Contraindications to Prednisolone
Do not use prednisolone if any of the following are present:
- Active infection or sepsis 1
- Active gastrointestinal bleeding 1, 2
- Acute renal failure 1, 2
- Acute pancreatitis 1, 2
- Uncontrolled infection 2
Treatment Protocol
Standard dosing regimen:
- Prednisolone 40 mg orally once daily for 28 days 1, 2
- Assess response at day 7 using the Lille model score 1
- If Lille score <0.56 (responder): continue full 28-day course, then consider tapering over 2 weeks 1
- If Lille score ≥0.56 (null responder): discontinue prednisolone immediately to reduce infection risk 3
Evidence Supporting Prednisolone Over Other Glucocorticoids
- A landmark 1989 multicenter trial demonstrated that methylprednisolone reduced 28-day mortality from 35% to 6% (p=0.006) in severe alcoholic hepatitis 4
- However, current guidelines uniformly recommend prednisolone rather than methylprednisolone because prednisolone is the active form and avoids the need for hepatic conversion 1
- The STOPAH trial (2015, n=1053) showed prednisolone was associated with reduced 28-day mortality (odds ratio 0.72,95% CI 0.52-1.01, p=0.06), though this did not reach statistical significance 5
Common Pitfall: Infection Risk
Critical caveat: Serious infections occur in 13% of patients treated with prednisolone versus 7% without prednisolone (p=0.002) 5
- Continuous monitoring for infections is mandatory, as they develop frequently after treatment initiation and are associated with high mortality, particularly in steroid non-responders 2
- Discontinuing steroids in non-responders is critical as infection occurs more frequently in this population 2
Alternative When Prednisolone is Contraindicated
- Pentoxifylline 400 mg three times daily for 28 days can be considered when steroids are contraindicated, though it is less effective than prednisolone 1, 3
- Pentoxifylline showed inferior 1-month survival (74.5%) compared to prednisolone (87.0%) in head-to-head comparison 3
- Pentoxifylline does NOT work as rescue therapy for steroid non-responders and should not be used in this setting 3
Adjunctive Therapies (Not Recommended as Standard)
- N-acetylcysteine combined with prednisolone improved 1-month survival (8% vs 24%, p=0.006) but not 6-month survival (27% vs 38%, p=0.07) in one trial 6
- The combination is not consistently recommended due to lack of long-term benefit, though it may reduce hepatorenal syndrome deaths 1, 6
- Pentoxifylline added to prednisolone showed no survival benefit at 6 months (69.9% vs 69.2%, p=0.91) 7