What are the criteria for initiating prednisolone in a patient with alcoholic hepatitis, including severity score thresholds and contraindications?

Criteria to Start Prednisolone in Alcoholic Hepatitis

Prednisolone 40 mg daily for 28 days should be initiated in patients with severe alcoholic hepatitis defined by a Maddrey Discriminant Function (mDF) score ≥32, MELD score >21, or Glasgow Alcoholic Hepatitis Score (GAHS) ≥9, or the presence of hepatic encephalopathy, provided that active infection, gastrointestinal bleeding, renal failure, pancreatitis, and uncontrolled infection have been definitively excluded. 1

Severity Score Thresholds for Treatment

The decision to initiate prednisolone hinges on objective severity assessment:

• mDF ≥32: This is the most widely validated threshold, calculated as 4.6 × (patient PT - control PT in seconds) + total bilirubin (mg/dL). An mDF ≥32 predicts 40-50% mortality at 90 days without treatment and represents the primary indication for corticosteroid therapy. 1, 2

• MELD >21: Alternative severity marker that incorporates bilirubin, INR, and creatinine. A MELD >21 indicates high short-term mortality and confirms severe disease warranting treatment. 1

• GAHS ≥9: Another validated prognostic model that can be used to identify treatment candidates. 1

• Hepatic encephalopathy: The presence of spontaneous hepatic encephalopathy, regardless of score, is an indication for treatment. 1, 3

The evidence supporting these thresholds comes from pooled primary data showing 28-day survival of 84.6% with steroids versus 65% with placebo in patients meeting these criteria—a 30% relative risk reduction with a number needed to treat of 5. 1

Mandatory Contraindication Screening Before Initiation

Active infection must be definitively excluded before starting corticosteroids, as infection occurs in 20-30% of severe alcoholic hepatitis cases and is the primary driver of multi-organ failure and death. 2, 4

Required screening includes:

• Blood cultures (must be negative or already obtained and pending) 2
• Urine culture and urinalysis 2
• Chest radiograph to exclude pneumonia 2
• Diagnostic paracentesis with ascitic fluid culture if ascites is present 2, 4
• Assessment for active gastrointestinal bleeding 1
• Hepatitis B and C screening, tuberculosis assessment when risk factors exist 2

Absolute contraindications to prednisolone:

• Active gastrointestinal bleeding 1
• Uncontrolled or active infection 1, 2
• Acute pancreatitis 1, 4
• Renal failure (typically defined as creatinine >2.5 mg/dL, though some guidelines use lower thresholds) 1

The rationale is clear: corticosteroids were excluded in patients with these conditions in the pivotal trials demonstrating efficacy, and their use in these contexts may cause more harm than benefit. 1

Treatment Protocol and Response Assessment

Once contraindications are excluded and severity criteria met:

• Dosing: Prednisolone 40 mg orally daily (or methylprednisolone 32 mg IV daily if unable to take oral) for 28 days, followed by either abrupt discontinuation or a 2-week taper. 1, 4

• Day 7 response assessment: Calculate the Lille score on day 7 of treatment to determine whether to continue therapy. 1, 2, 4

  • Lille score <0.45: Continue prednisolone for full 28 days (85% 6-month survival expected) 1, 4
  • Lille score ≥0.45: Discontinue prednisolone immediately (non-responders derive no benefit and face increased infection risk) 1, 4
  • Lille score ≥0.56: Definite non-responders with only 53.3% 28-day survival; stopping steroids is mandatory 1, 4

The Lille model incorporates age, albumin, change in bilirubin from day 0 to day 7, renal function, baseline bilirubin, and prothrombin time. 1, 4

Essential Concurrent Supportive Measures

Prednisolone is never monotherapy. All patients must receive:

• Absolute alcohol abstinence (the single most important intervention) 1, 2, 4
• Aggressive nutritional support: 30-40 kcal/kg/day and 1.0-1.5 g protein/kg body weight, preferably via enteral route 1, 2, 4
• Thiamine 500 mg IV three times daily for 3-5 days before any glucose-containing fluids to prevent Wernicke's encephalopathy 2, 5, 4
• Vitamin and mineral supplementation: vitamin A, B12, folic acid, pyridoxine, vitamin D, and zinc 1, 4

Common Pitfalls to Avoid

• Starting steroids without infection screening: This is the most dangerous error, as occult infection under corticosteroids dramatically increases mortality. 2, 4

• Continuing steroids in non-responders: Patients with Lille score ≥0.45 should have steroids stopped immediately; continuing therapy only increases infection risk without survival benefit. 1, 4

• Using pentoxifylline as an alternative or adjunct: Multiple large trials show no survival benefit and no reduction in hepatorenal syndrome when combined with corticosteroids; it should not be used. 4

• Ignoring the upper threshold: Some evidence suggests patients with mDF >54 may have worse outcomes with steroids than without, though this threshold requires confirmation. 1

Adjunctive Considerations

• N-acetylcysteine (NAC): May be added to prednisolone as adjunctive therapy. One randomized trial showed improved 1-month survival (8% vs 24% mortality, P=0.006) and reduced hepatorenal syndrome (9% vs 22%, P=0.02), though 6-month survival (the primary endpoint) was not significantly improved (27% vs 38%, P=0.07). 6 NAC is not recommended as monotherapy. 2

• S-adenosylmethionine: Limited evidence suggests potential benefit when combined with prednisolone, with better response rates and less hepatorenal syndrome, but requires further validation. 7