Prednisolone Dosing for Alcoholic Hepatitis
For severe alcoholic hepatitis (Maddrey Discriminant Function ≥32), the recommended dose is prednisolone 40 mg daily for 28 days, typically followed by discontinuation or a 2-week taper. 1, 2
Patient Selection for Steroid Therapy
Severe disease criteria (any of the following):
- Maddrey Discriminant Function (MDF) score ≥32 1
- MELD score >20-21 1, 2
- Glasgow Alcoholic Hepatitis Score (GAHS) ≥9 2
- Presence of hepatic encephalopathy 1
Mild-moderate disease (MDF <32, MELD <18, GAHS <8) typically improves with abstinence and nutritional support alone and does not require steroid therapy. 1, 2
Timing of Steroid Initiation
Do not rush to start steroids immediately. The median time from admission to steroid initiation in clinical trials was 6.5 days, allowing for thorough evaluation and exclusion of contraindications. 3 This systematic approach is critical to avoid treating patients with occult infections or other contraindications.
Before initiating steroids, complete the following:
- Screen for infection with chest x-ray, blood, urine, and ascites cultures 1
- Obtain abdominal ultrasound with Doppler to exclude other causes of jaundice 1, 4
- Ensure serum creatinine is <2.5 mg/dL 1
- Rule out active gastrointestinal bleeding 1, 2
Absolute Contraindications to Steroid Therapy
Do not use steroids if any of the following are present:
- Active infection or sepsis 1, 2, 4
- Uncontrolled gastrointestinal bleeding 1, 2, 4
- Acute kidney injury with serum creatinine >2.5 mg/dL 1
- Acute pancreatitis 1, 2, 4
- Concomitant diseases including HBV, HCV, drug-induced liver injury, hepatocellular carcinoma, HIV, or tuberculosis 1
Treatment Protocol
Standard regimen: Prednisolone 40 mg orally once daily for 28 days. 1, 2, 4 This dose was used in the landmark trials that demonstrated improved short-term survival (84.6% vs 65.1% with placebo), representing a 30% relative risk reduction and a number needed to treat of 5. 1, 4
Alternative formulation: Methylprednisolone 32 mg daily can be used if prednisolone is unavailable, as demonstrated in the Carithers trial showing 6% mortality with steroids versus 35% with placebo at 28 days. 5
Response Assessment at Day 7
Calculate the Lille score at day 7 to determine whether to continue or discontinue steroids. 1, 2, 6
Lille score interpretation:
- Complete responders (Lille ≤0.16): 91.1% 28-day survival—continue full 28-day course 2, 6
- Partial responders (Lille 0.16-0.56): 79.4% 28-day survival—continue full 28-day course 2
- Null responders (Lille ≥0.56): 53.3% 28-day survival—discontinue steroids immediately due to increased infection risk without benefit 2, 6
Steroid Tapering
After completing 28 days of prednisolone 40 mg daily, taper over 2 weeks. 1, 4 This is the most frequently reported regimen in clinical trials and minimizes steroid exposure while preventing adrenal insufficiency. 3
A common taper schedule: 20 mg daily for 4 days, 10 mg daily for 4 days, then 5 mg daily for 4 days. 1
Monitoring During Treatment
Vigilant monitoring is essential during the first month of treatment when most adverse events occur, particularly infections. 3
Common adverse events to monitor:
Serious infections occurred in 13% of patients treated with prednisolone versus 7% of those not receiving prednisolone. 7
Alternative Therapy
Pentoxifylline 400 mg orally three times daily for 28 days can be considered only when steroids are contraindicated. 1, 2 However, pentoxifylline is inferior to prednisolone, with 1-month survival of 74.5% versus 87.0% with prednisolone. 6 The STOPAH trial showed pentoxifylline did not improve survival (odds ratio 1.07,95% CI 0.77-1.49, P=0.69). 7
Combination therapy with pentoxifylline plus prednisolone offers no additional benefit over prednisolone alone, with identical 6-month survival rates (69.9% vs 69.2%, P=0.91). 8
Critical Pitfall to Avoid
Do not initiate steroids without first systematically excluding infections and other contraindications. Taking up to one week for thorough evaluation is appropriate and reflects actual clinical trial practice. 3 Patients with very high disease severity (MDF >90 or MELD >30) require especially careful assessment for occult infection before steroid initiation. 4
Long-Term Outcomes
Long-term survival depends primarily on achieving complete alcohol abstinence, which should be strongly recommended to all patients. 2, 4 The 6-month survival rate is 82% in patients with confirmed early change in bilirubin level but only 23% in those without this response. 2