What is the appropriate treatment approach for suspected severe alcoholic hepatitis?

Management of Suspected Severe Alcoholic Hepatitis

For suspected severe alcoholic hepatitis, immediately assess disease severity using Maddrey Discriminant Function (mDF) or MELD score, then initiate prednisolone 40 mg daily for 28 days if mDF ≥32 or MELD >20 and no contraindications exist, while simultaneously implementing alcohol abstinence and aggressive nutritional support. 1, 2

Initial Assessment and Severity Stratification

Calculate severity scores immediately upon presentation:

• Use mDF ≥32 or MELD >20 to define severe disease requiring pharmacologic intervention 1, 2
• Severe alcoholic hepatitis carries 30-50% mortality at 28 days without treatment 1
• Alternative thresholds include Glasgow Alcoholic Hepatitis Score (GAHS) ≥9 2

Screen for infections and contraindications before starting steroids:

• Obtain blood, urine, and ascites cultures (if present) regardless of fever presence 1
• Active gastrointestinal bleeding, renal failure, acute pancreatitis, and uncontrolled infection are absolute contraindications to corticosteroids 2
• Consider transjugular liver biopsy for definitive diagnosis when the clinical picture is unclear, especially before committing to corticosteroid therapy 1

Universal Interventions (All Patients)

Implement these measures regardless of disease severity:

• Mandate complete and permanent alcohol abstinence—this is the single most important intervention 3, 2
• Provide aggressive nutritional support: 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day 1, 3, 2
• Use enteral feeding via nasogastric tube if the patient cannot eat due to anorexia or altered mental status 1
• Administer thiamine 500 mg IV three times daily for 3-5 days before any glucose-containing solutions to prevent Wernicke's encephalopathy 3
• Supplement with B vitamins and folic acid 1

Pharmacologic Treatment for Severe Disease

For patients with mDF ≥32 or MELD >20 without contraindications:

Corticosteroid Therapy

• Initiate prednisolone 40 mg orally daily for 28 days 4, 1, 2
• Take up to 6-7 days from admission to systematically evaluate for contraindications before starting steroids 5
• This improves 28-day survival by reducing pro-inflammatory cytokines including TNF-α 2

Response Assessment at Day 7

• Calculate the Lille score at day 7 of treatment 4, 1
• Lille score <0.45 indicates response; continue steroids for full 28-day course 4, 2
• Lille score ≥0.45 indicates non-response; immediately discontinue steroids 4, 2
• Non-responders have 6-month survival of only 25% and increased infection risk 4
• Complete responders (Lille ≤0.16) have 91.1% 28-day survival, partial responders (0.16-0.56) have 79.4%, and null responders (≥0.56) have only 53.3% 4

Steroid Tapering

• After completing 28 days, taper over 2 weeks using the lowest possible steroid exposure 5
• Prednisolone can be continued for an additional 21 days with or without tapering in responders 4

Adjunctive Therapy

• Consider N-acetylcysteine in combination with corticosteroids, which has shown short-term survival benefit at 1 and 3 months 1

Alternative Treatment When Steroids Are Contraindicated

If steroids cannot be used due to infection, renal failure, or other contraindications:

• Administer pentoxifylline 400 mg orally three times daily for 28 days 4
• However, recognize that pentoxifylline is inferior to prednisolone (1-month survival 74.5% vs 87.0%) 4
• Pentoxifylline may reduce hepatorenal syndrome-related deaths 4
• Do not use pentoxifylline as rescue therapy in steroid non-responders—it provides no benefit when switched early 4
• Do not combine steroids and pentoxifylline—combination therapy shows no survival benefit 4

Critical Monitoring and Complication Prevention

Vigilant surveillance is essential, particularly in the first month:

• Monitor closely for infections, which occur more frequently in steroid non-responders and account for most deaths in the weeks following steroid treatment 4, 2, 6
• Infections, gastrointestinal bleeding, and renal impairment are the most common adverse events 5
• Avoid all nephrotoxic drugs including diuretics, as acute kidney injury represents early multi-organ failure with very high mortality 1, 3, 2
• Avoid iodinated contrast agents which increase acute kidney injury risk 1, 3
• Serious infections occur in 13% of prednisolone-treated patients versus 7% without prednisolone 7

Liver Transplantation Evaluation

For patients with very severe disease or steroid non-responders:

• Refer patients with MELD >26 for early liver transplantation evaluation 1, 3
• The 90-day mortality without transplantation is extremely high in this population 1
• Survival may be significantly higher after liver transplantation than with continued medical treatment in null responders 4
• Select patients with good insight into their alcohol use disorder and strong social support 1
• Traditional 6-month abstinence requirement may be waived in severe alcoholic hepatitis cases 3

Common Pitfalls to Avoid

• Do not delay severity assessment—calculate mDF or MELD immediately upon presentation 1, 2
• Do not rush to start steroids—take up to a week to systematically screen for infections and contraindications 5
• Do not continue steroids in non-responders—Lille score ≥0.45 at day 7 mandates immediate discontinuation due to infection risk without benefit 4, 2
• Do not use pentoxifylline as rescue therapy after steroid failure—it provides no survival benefit 4
• Do not overlook nutritional support—protein-calorie malnutrition is present in almost every patient with severe alcoholic hepatitis and enteral nutrition improves survival regardless of steroid treatment 3, 6
• Do not use diuretics or nephrotoxic agents—acute kidney injury dramatically worsens prognosis 1, 3, 2