Should a patient with alcoholic hepatitis superimposed on cirrhosis and severe disease (Maddrey’s discriminant function >32, MELD ≥20, bilirubin >5 mg/dL) without contraindications be treated with prednisolone 40 mg daily for 28 days, and how should response be assessed and therapy managed?

Prednisolone in Alcoholic Hepatitis with Cirrhosis

Direct Recommendation

Yes, initiate prednisolone 40 mg orally daily for 28 days immediately after excluding active infection, gastrointestinal bleeding, acute pancreatitis, and severe renal failure (creatinine >2.5 mg/dL). 1, 2

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Treatment Algorithm

Step 1: Confirm Severity and Indications

Your patient meets criteria for severe alcoholic hepatitis requiring corticosteroid therapy:

• Maddrey Discriminant Function ≥32 (calculated as 4.6 × [PT – control PT] + bilirubin in mg/dL) 1, 2
• MELD ≥20 (your patient has MELD ≥20, which predicts 40-50% 90-day mortality without treatment) 1, 2
• Bilirubin >5 mg/dL (confirms severe disease) 1

The presence of underlying cirrhosis does not contraindicate steroid therapy—in fact, 79% of patients in major cohorts had cirrhosis, and the landmark 1992 trial included 57 of 61 patients with biopsy-proven cirrhosis who still benefited from prednisolone. 3, 4

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Step 2: Mandatory Pre-Treatment Screening

Before starting prednisolone, you must exclude absolute contraindications: 1, 5, 2

• Active infection (obtain blood cultures, urine cultures, chest X-ray, and diagnostic paracentesis with ascitic fluid culture if ascites present—infection occurs in 20-30% of severe cases and drives multi-organ failure) 5, 2
• Active gastrointestinal bleeding 1, 2
• Acute pancreatitis 1, 2
• Severe renal failure (creatinine >2.5 mg/dL is a contraindication; below this threshold, proceed with close renal monitoring) 2

Critical pitfall: Starting steroids without infection screening exposes patients to 25% risk of developing infection during the first month of treatment, which dramatically increases mortality. 5

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Step 3: Initiate Prednisolone Protocol

• Dose: Prednisolone 40 mg orally once daily (or methylprednisolone 32 mg IV if unable to take oral medications) 1, 5, 2
• Duration: 28 days, followed by either abrupt discontinuation or a 2-week taper 1, 5
• Evidence: Prednisolone improves 28-day survival from 55% (placebo) to 88% in severe alcoholic hepatitis (number needed to treat = 5). 3 A worldwide study of 3,380 patients confirmed that corticosteroids decrease 30-day mortality by 41% (HR 0.59, p <0.001). 4

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Step 4: Day 7 Response Assessment (Lille Score)

On day 7 of treatment, calculate the Lille score using age, albumin at day 0, change in bilirubin from day 0 to day 7, renal function, baseline bilirubin, and prothrombin time: 1, 5, 2

• Lille score <0.45 → Continue prednisolone for the full 28 days (expected 6-month survival 85%) 5, 2
• Lille score 0.45-0.56 → Consider stopping on a case-by-case basis (partial responders, 79.4% 28-day survival) 1, 5
• Lille score ≥0.56 → Stop prednisolone immediately (null responders have only 53.3% 28-day survival and derive no benefit from continued steroids, only increased infection risk) 1, 5

Critical pitfall: Continuing steroids in non-responders (Lille ≥0.56) is a common error that exposes patients to infection without survival benefit and delays consideration of early liver transplantation evaluation. 5

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Step 5: Essential Concurrent Supportive Care

All patients receiving prednisolone must also receive: 1, 5, 2

• Absolute alcohol abstinence (the single most important intervention for long-term outcomes; 6-month survival is 82% with abstinence vs. 23% without) 1, 2
• Thiamine 500 mg IV three times daily for 3-5 days before any glucose-containing fluids to prevent Wernicke's encephalopathy 2
• Aggressive nutritional support: 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day via enteral route 1, 5, 2
• Vitamin supplementation: thiamine, vitamin B12, folic acid, pyridoxine, vitamin D, and zinc 5
• Avoid nephrotoxic drugs including diuretics 5

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Step 6: Ongoing Infection Surveillance

Screen repeatedly for infection during hospitalization because infection develops in 25% of patients during the first month of corticosteroid treatment and is associated with increased short-term mortality: 5

• Repeat blood cultures, urine cultures, and chest imaging if clinical deterioration occurs 5
• Maintain high index of suspicion for spontaneous bacterial peritonitis if ascites present 5, 2

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Therapeutic Window and Upper Limits

Prednisolone is most effective in patients with MELD 25-39 (21-30% survival benefit), with benefit extending from MELD 21 to MELD 51. 4 Patients with MELD >51 derive no survival benefit from corticosteroids. 4 Some data suggest patients with Maddrey Discriminant Function >54 may experience worse outcomes with steroids, though this threshold requires further validation. 2

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Alternative Therapies (Not Recommended)

• Pentoxifylline should not be used as an alternative or adjunct to prednisolone—the STOPAH trial (1,103 patients) showed no survival benefit at 28 days, 90 days, or 1 year (OR 1.07, p=0.69). 5, 6
• N-acetylcysteine may be considered as an adjunct to prednisolone for modest additional benefit, but is not recommended as monotherapy. 2

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Nuances and Divergent Evidence

The STOPAH trial (2015) showed prednisolone was associated with a reduction in 28-day mortality that did not reach statistical significance (14% vs. 17%, OR 0.72, p=0.06), with no improvement at 90 days or 1 year. 6 However, this trial has been criticized for including patients with milder disease (median MELD 21) and for high rates of serious infections (13% with prednisolone vs. 7% without). 6 In contrast, the 1992 landmark trial and the 2021 worldwide study (3,380 patients) both demonstrated clear survival benefit. 3, 4 Current guidelines from the American Association for the Study of Liver Diseases and American College of Gastroenterology continue to recommend prednisolone as standard therapy for severe alcoholic hepatitis. 1, 5, 2