When to start steroids in patients with alcoholic hepatitis?

When to Start Steroids in Alcoholic Hepatitis

Start prednisolone 40 mg daily for 28 days in patients with severe alcoholic hepatitis (Maddrey Discriminant Function ≥32 or MELD >20-21) after taking up to one week to systematically exclude contraindications, particularly active infection, gastrointestinal bleeding, acute renal failure, and acute pancreatitis. 1, 2, 3, 4

Defining Severe Disease: The Threshold for Treatment

Steroids should be initiated when patients meet criteria for severe alcoholic hepatitis using any of these validated scoring systems: 2, 3

• Maddrey Discriminant Function (mDF) ≥32 1, 2
• MELD score >20-21 3, 5
• Glasgow Alcoholic Hepatitis Score (GAHS) ≥9 2, 3
• Presence of hepatic encephalopathy 1

Patients with mild-to-moderate disease (mDF <32, MELD <18-20) improve with abstinence and nutritional support alone and should not receive steroids. 1, 2

Critical Pre-Treatment Evaluation Period

The most important finding from recent evidence is that you should take up to 6-7 days from admission to systematically evaluate patients before initiating steroids. 4 This pre-treatment window allows you to:

• Screen for active infections with blood cultures, urine cultures, and ascitic fluid culture if ascites is present 3, 4
• Assess for gastrointestinal bleeding through clinical examination and laboratory monitoring 1, 3
• Evaluate renal function to identify acute kidney injury or hepatorenal syndrome 1, 3
• Rule out acute pancreatitis with lipase levels and imaging if indicated 3
• Monitor bilirubin trends during the first week, as improvement suggests patients may not require steroids 1

The median time from admission to steroid initiation across 28 clinical trials was 6.5 days, supporting this systematic approach rather than immediate treatment. 4

Absolute Contraindications to Steroid Therapy

Do not start steroids if any of the following are present: 1, 3

• Active infection or sepsis (most critical contraindication) 1, 3
• Active gastrointestinal bleeding 1, 3
• Acute renal failure 1, 3
• Acute pancreatitis 3
• Uncontrolled infection despite negative initial cultures 3

In these situations, use pentoxifylline 400 mg three times daily for 28 days as an alternative, though it is less effective (74.5% vs 87.0% one-month survival). 1, 2, 6

The Therapeutic Window: MELD Score Matters

Steroids are only effective in patients with MELD scores between 21 and 51, with maximal benefit seen in MELD 25-39. 5 This represents critical evidence from a worldwide study of 3,380 patients:

• MELD 21-24: Steroids provide modest survival benefit (HR 0.61) 5
• MELD 25-39: Maximum steroid effect with 21-30% survival benefit (HR 0.57-0.58) 5
• MELD 40-51: Diminishing benefit but still some effect (HR 0.72) 5
• MELD >51: No survival benefit from steroids 5

This means patients who are "too sick" (MELD >51) should not receive steroids and should be evaluated urgently for liver transplantation instead. 5

Standard Dosing Regimen

Once contraindications are excluded and severity criteria are met: 1, 2, 3

• Prednisolone 40 mg orally daily (or methylprednisolone 32 mg IV if unable to take oral) 3
• Duration: 28 days 1, 2, 3
• Assess response at day 7 using Lille score or Early Change in Bilirubin Level 1, 2, 3

Early Response Assessment: The Day 7 Decision Point

At day 7, calculate the Lille score (available at www.lillemodel.com) to determine whether to continue or stop steroids: 1, 2, 3, 6

• Lille score ≤0.16 (complete responders): 91.1% 28-day survival—continue full 28-day course 1, 2, 6
• Lille score 0.16-0.56 (partial responders): 79.4% 28-day survival—continue full 28-day course 1, 2
• Lille score ≥0.56 (null responders): 53.3% 28-day survival—stop steroids immediately to avoid infection risk without benefit 1, 2, 3, 6

Alternatively, use Early Change in Bilirubin Level (ECBL): patients with confirmed ECBL have 82% six-month survival versus only 23% without ECBL. 2

Essential Concurrent Interventions

All patients receiving steroids must also receive: 3

• Complete alcohol abstinence (counseling and support) 1, 3
• Aggressive enteral nutrition: 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day 1, 3
• Vitamin supplementation: thiamine, B12, folic acid, pyridoxine, vitamin D, zinc 3
• Avoid nephrotoxic drugs including diuretics 3

Post-Treatment Management

After completing 28 days of prednisolone: 1, 4

• Taper over 2 weeks (most common and recommended regimen) 1, 4
• Monitor closely in first month as most infections occur during this period 4
• Close outpatient follow-up to minimize steroid exposure 4

Common Pitfalls and Critical Caveats

Infection surveillance is paramount: Exactly 50% of adverse events in steroid trials occurred in the treatment arm, with infections being the most common complication. 4 Most infections develop within the first month of treatment. 4

Do not use combination therapy: Prednisolone plus pentoxifylline provides no additional survival benefit over prednisolone alone at 4 weeks or 6 months. 1, 7

Do not switch to pentoxifylline in non-responders: Early switching from steroids to pentoxifylline in patients without ECBL shows no survival benefit (35.5% vs 31.0% two-month survival). 1

Consider liver transplantation for null responders: Patients with Lille score ≥0.56 have significantly higher survival with transplantation than continued medical therapy. 1, 6

Long-term survival depends on abstinence: While steroids improve 30-day survival (88% vs 65% without treatment), they do not improve 90-day or 180-day survival unless patients achieve complete alcohol abstinence. 3, 5