What is the recommended treatment protocol for administering methylprednisolone (methylprednisolone) intravenously (IV) in a patient with severe alcohol-induced hepatitis?

Administration of Methylprednisolone 32 mg IV Daily in Severe Alcohol-Induced Hepatitis

Administer methylprednisolone 32 mg intravenously once daily for 28 days, followed by either abrupt discontinuation or a 2-week taper, after confirming the absence of contraindications and active infections. 1

Pre-Treatment Requirements

Before initiating methylprednisolone, you must complete the following screening within the first 6-7 days of admission 2:

• Infection screening: Obtain blood cultures, urine cultures, and ascitic fluid culture (if ascites present) to rule out active infection 1
• Exclude absolute contraindications: Active gastrointestinal bleeding, uncontrolled infection/sepsis, acute renal failure, or acute pancreatitis 3, 1
• Confirm severity: Verify mDF ≥32 (the patient meets this criterion) 3, 1

The median time from admission to steroid initiation in clinical trials is 6.5 days, allowing adequate time for systematic evaluation 2.

Dosing Protocol

The standard regimen is methylprednisolone 32 mg IV once daily, which is equivalent to prednisolone 40 mg orally 1:

• Continue for 28 days total 1, 4
• After 28 days, either discontinue abruptly or taper over 2 weeks 5, 1
• The 2-week taper is the most commonly reported regimen and minimizes steroid exposure 2

This dosing is based on the landmark 1989 multicenter trial showing 6% mortality with methylprednisolone versus 35% with placebo (p=0.006) 4.

Mandatory Day 7 Response Assessment

At day 7, calculate the Lille score to determine whether to continue or discontinue steroids 5, 3, 1:

• Lille score <0.45 (or <0.56 by some criteria): Continue steroids for full 28 days—these patients have 85% 6-month survival 5, 1
• Lille score ≥0.45 (or ≥0.56): Discontinue steroids immediately—continuing exposes patients to infection risk without survival benefit 5, 1

The Lille model categorizes patients as complete responders (≤0.16,91.1% 28-day survival), partial responders (0.16-0.56,79.4% survival), or null responders (≥0.56,53.3% survival) 5, 3. Infections occur more frequently in steroid non-responders, making early discontinuation critical 5, 6.

Essential Concurrent Supportive Care

All patients receiving methylprednisolone must receive 1, 6:

• Complete alcohol abstinence: No safe amount exists after alcoholic hepatitis 6
• Aggressive enteral nutrition: 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day via enteral route 1, 6
• Vitamin supplementation: Thiamine, vitamin B12, folic acid, pyridoxine, vitamin D, and zinc 1
• Avoid nephrotoxic drugs: Including diuretics and iodinated contrast agents 1, 6

Enteral nutrition improves survival regardless of steroid treatment 6.

Monitoring for Complications

Vigilant monitoring is required during the first month of treatment, when most infections occur 2:

• Serious infections occur in 13% of patients treated with prednisolone versus 7% without prednisolone (p=0.002) 7
• Monitor for gastrointestinal bleeding, renal impairment, and new infections 2
• Acute kidney injury represents early multi-organ failure and dramatically worsens prognosis 6

Common Pitfalls to Avoid

• Do not combine with pentoxifylline: Multiple large trials show no survival benefit when pentoxifylline is added to corticosteroids, and no reduction in hepatorenal syndrome 1, 7, 8. The 2015 STOPAH trial (n=1,053) found pentoxifylline had an odds ratio of 1.07 for 28-day mortality (95% CI 0.77-1.49, p=0.69) 7.
• Do not continue steroids beyond day 7 in non-responders: This exposes patients to infection without benefit 1
• Do not delay infection screening: Infections can develop after initial diagnosis and are associated with high mortality 6

Alternative if Contraindications Exist

If steroids are contraindicated, consider pentoxifylline 400 mg orally three times daily for 28 days, though it is less effective than prednisolone 5, 3. A Korean randomized trial showed 1-month survival of 74.5% with pentoxifylline versus 87.0% with prednisolone, failing to demonstrate non-inferiority 5.

Long-Term Outcome Determinant

Long-term survival depends primarily on achieving permanent alcohol abstinence 1. Consider naltrexone or acamprosate combined with counseling to reduce relapse risk 6. For steroid non-responders with Lille score ≥0.56, liver transplantation should be considered as a rescue therapy 5.