What is the recommended prednisolone (corticosteroid) dosing regimen for the treatment of alcoholic hepatitis?

Prednisolone Dosing for Alcoholic Hepatitis

Prednisolone 40 mg daily for 28 days is the recommended dosing regimen for severe alcoholic hepatitis (defined as Maddrey Discriminant Function ≥32, MELD >20, or presence of hepatic encephalopathy). 1

Severity Assessment

Before initiating treatment, severity assessment is crucial:

• Severe alcoholic hepatitis (requires corticosteroid treatment):

  • Maddrey Discriminant Function (MDF) ≥32
  • MELD score >20
  • Glasgow alcoholic hepatitis score ≥9
  • Presence of hepatic encephalopathy

• Mild alcoholic hepatitis (supportive care only):

  • MDF <32
  • MELD ≤18
  • Improving liver function tests during hospitalization

Treatment Algorithm

1. Assess severity using validated scoring systems

2. Check for contraindications to steroids:

   • Gastrointestinal bleeding
   • Renal failure
   • Pancreatitis
   • Uncontrolled infection
   • Hepatitis B virus infection
   • Tuberculosis 1

3. For severe alcoholic hepatitis:

   • If no contraindications: Prednisolone 40 mg daily for 28 days 2, 1
   • If contraindicated: Pentoxifylline 400 mg three times daily for 28 days 2, 1

4. Monitor response to treatment:

   • Assess at day 7 using Early Change in Bilirubin Level (ECBL) or Lille model
   • If Lille score ≥0.56 (null responder) or no ECBL: Consider discontinuing steroids 2
   • If Lille score <0.56: Continue prednisolone for full 28-day course 2

Evidence for Prednisolone Dosing

The recommended 40 mg daily dose of prednisolone is supported by multiple clinical trials and guidelines:

• The American Association for the Study of Liver Diseases recommends prednisolone 40 mg daily for 28 days in severe alcoholic hepatitis 1
• The KASL clinical practice guidelines recommend the same dosing regimen 2
• The Hepatology guidelines from 2010 reviewed 13 clinical trials of steroids in alcoholic hepatitis, with most using 40 mg daily of prednisolone for 28-30 days 2

The most recent large randomized controlled trial (STOPAH) used prednisolone 40 mg daily for 28 days and found a reduction in 28-day mortality, though this benefit did not persist beyond this timeframe 3, 4.

Important Considerations

• Infection risk: Serious infections occurred in 13% of patients treated with prednisolone compared to 7% in controls 4. Monitor closely for infections.

• Response assessment: The Lille model at day 7 is crucial for determining whether to continue treatment. A score ≥0.56 indicates null response and consideration for discontinuing steroids 2.

• Abstinence: Complete abstinence from alcohol is essential for all patients with alcoholic hepatitis, as outcomes are significantly better in those who maintain abstinence 1.

• Nutritional support: Ensure adequate protein intake (1.2-1.5 g/kg/day) and caloric intake (35-40 kcal/day) 1.

• Avoid nephrotoxic drugs: Acute kidney injury is an early manifestation of multi-organ failure in alcoholic hepatitis 1.

Pentoxifylline as Alternative

If steroids are contraindicated, pentoxifylline 400 mg three times daily for 28 days can be considered, though evidence suggests it is less effective than prednisolone 2, 5. The STOPAH trial found that pentoxifylline did not improve survival in patients with alcoholic hepatitis 3, 4.