What is the recommended prednisone dosage and regimen for severe alcoholic hepatitis with a Maddrey's discriminant function greater than 33?

Prednisolone 40 mg Daily for 28 Days in Severe Alcoholic Hepatitis

For severe alcoholic hepatitis with a Maddrey's discriminant function greater than 33, the standard evidence-based regimen is prednisolone 40 mg orally once daily for 28 days. 1, 2

Dosing Regimen

• Prednisolone 40 mg orally once daily is the recommended dose, not prednisone 1, 2
• Duration: 28 days of continuous therapy 3, 1
• Alternative: Methylprednisolone 32 mg IV daily if oral intake is impossible 2, 4
• After 28 days, either abrupt discontinuation or a 2-week taper may be used 1, 2

Critical Pre-Treatment Requirements

Before initiating corticosteroids, you must exclude absolute contraindications:

• Active infection (obtain blood cultures, urine cultures, chest X-ray, and diagnostic paracentesis if ascites present) 3, 2, 4
• Active gastrointestinal bleeding 3, 2
• Renal failure (serum creatinine > 2.5 mg/dL is an absolute contraindication) 2
• Acute pancreatitis 2
• Uncontrolled infection or multiorgan failure 1

Infection occurs in 20-30% of severe alcoholic hepatitis cases and is the primary driver of multiorgan failure and death, making pre-treatment screening mandatory. 2, 4

Why Prednisolone, Not Prednisone

Prednisolone is strongly preferred over prednisone because it is the active drug and does not require hepatic conversion, which is impaired in alcoholic hepatitis. 1 Using prednisone instead of prednisolone is a common pitfall that reduces treatment efficacy. 1

Day-7 Response Assessment: The Lille Score

On day 7 of treatment, calculate the Lille score to determine whether to continue or stop steroids:

• Lille score < 0.45: Continue the full 28-day course (6-month survival ≈ 85%) 3, 1, 4
• Lille score ≥ 0.45: Consider discontinuing steroids (non-responders) 3, 4
• Lille score ≥ 0.56: Stop steroids immediately (null responders; 28-day survival only 53.3%; continued steroids increase infection risk without survival benefit) 3, 1, 4

The Lille score incorporates age, albumin, change in bilirubin from day 0 to day 7, renal function, baseline bilirubin, and prothrombin time. 2, 4 This dynamic assessment is critical because continuing steroids in non-responders exposes patients to unnecessary infection risk without any survival benefit. 4

Expected Outcomes

• 28-day survival: 84.6% with steroids versus 65% with placebo (number needed to treat = 5) 2
• Historical mortality: A Maddrey score ≥ 32 predicted 40-50% one-month mortality without treatment 1, 2
• Contemporary mortality: With modern supportive care, one-month mortality is approximately 15-17% 1

Essential Concurrent Supportive Care

While on corticosteroids, provide:

• Absolute alcohol abstinence (the single most important intervention for long-term outcomes) 2, 4
• Aggressive nutritional support: 30-40 kcal/kg/day and 1.0-1.5 g protein/kg/day, preferably via enteral route 3, 2, 4
• Thiamine 500 mg IV three times daily for 3-5 days before any glucose-containing fluids to prevent Wernicke's encephalopathy 2
• Vigilant infection surveillance with low threshold for cultures, as infection risk increases during steroid therapy 1, 4

What NOT to Do

• Do not use pentoxifylline as an adjunct to prednisolone; multiple large trials show no survival benefit when combined with corticosteroids 3, 5, 6
• Do not continue steroids beyond day 7 in non-responders (Lille ≥ 0.45); this only increases infection risk without improving survival 3, 4
• Do not substitute prednisone for prednisolone; impaired hepatic conversion reduces efficacy 1

Monitoring During Treatment

• Repeat infection screening if clinical deterioration occurs, as 25% of patients develop infection during the first month of corticosteroid treatment 4
• Monitor for hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding, which are common decompensation events 2
• Assess renal function closely, especially if baseline creatinine is elevated 2

Special Considerations

• Patients with Maddrey score > 54 may experience worse outcomes with steroids, though this threshold requires further validation 2
• For patients with contraindications to steroids, pentoxifylline 400 mg orally three times daily for 28 days may be considered as an alternative, though it is less effective than prednisolone 3, 1
• Early liver transplantation evaluation should be considered for null responders (Lille ≥ 0.56) after careful selection 4