What is the recommended management for alcoholic hepatitis, including initial abstinence, severity assessment (Maddrey Discriminant Function and MELD scores), and indications for corticosteroid therapy?

Management of Alcoholic Hepatitis

Absolute alcohol abstinence is the cornerstone of treatment for all patients with alcoholic hepatitis, and for severe disease (MDF ≥32 or MELD >20), corticosteroids (prednisolone 40 mg daily or methylprednisolone 32 mg daily for 28 days) should be initiated after excluding active infection, with treatment response assessed at day 7 using the Lille score to determine whether to continue or stop therapy. 1, 2

Initial Assessment and Diagnosis

Diagnostic Criteria

• Onset of jaundice within 8 weeks of last drinking period in a patient with heavy alcohol use (>40 g/day or approximately 3 standard drinks daily) for more than 6 months 1, 2
• Serum bilirubin >3.0 mg/dL 1, 2
• Serum AST >50 IU/L but <400 IU/L with AST/ALT ratio >1.5 1, 2
• Liver biopsy is helpful but not required for clinical diagnosis 1

Mandatory Infection Screening Before Treatment

• Obtain blood cultures, urine cultures, and ascites fluid culture (if ascites present) regardless of fever presence, as the immune response is severely impaired in alcoholic hepatitis 1, 2
• Chest radiograph should be performed 3
• Active infection is an absolute contraindication to corticosteroid therapy 1, 3

Severity Assessment

Calculate Prognostic Scores

• Maddrey Discriminant Function (MDF) = 4.6 × (patient's PT - control PT in seconds) + serum bilirubin (mg/dL) 1, 2
  • MDF ≥32 predicts high 28-day mortality and defines severe disease 1, 2
• MELD score >20 predicts high 90-day mortality 1, 2
• Glasgow Alcoholic Hepatitis Score ≥9 also indicates severe disease 1, 3

Risk Stratification

• Patients with MDF <32 and MELD <20 have low risk and will likely improve with abstinence and supportive care alone 1
• Presence of systemic inflammatory response syndrome (SIRS) on admission indicates increased risk of multi-organ failure 1

Treatment Algorithm

All Patients (Mild and Severe)

• Enforce complete and permanent alcohol abstinence—there is no safe amount of alcohol consumption after an episode of alcoholic hepatitis 1, 2
• Provide aggressive nutritional support: 1-1.5 g protein/kg and 30-40 kcal/kg body weight daily 1, 2
• If oral intake is inadequate, place a feeding tube for enteral nutrition (parenteral nutrition alone is inadequate) 1
• Supplement with thiamine, vitamin B12, folic acid, pyridoxine, vitamin D, and zinc 3
• Avoid nephrotoxic drugs including diuretics, as acute kidney injury is an early manifestation of multi-organ failure 1, 3

Patients with Mild Disease (MDF <32 and MELD <20)

• Supportive care with abstinence counseling and high-protein diet 1
• Consider naltrexone or acamprosate combined with counseling to maintain abstinence 1
• Vitamin supplementation with B vitamins and folic acid 1

Patients with Severe Disease (MDF ≥32 or MELD >20)

Step 1: Exclude Contraindications to Corticosteroids

Absolute contraindications include: 1, 3

• Active or uncontrolled infection
• Active gastrointestinal bleeding
• Hepatitis B viral infection
• Tuberculosis or other serious infectious diseases
• Acute pancreatitis
• Renal failure

Step 2: Initiate Corticosteroid Therapy

• Methylprednisolone 32 mg IV daily (equivalent to prednisolone 40 mg oral) for 28 days 1, 3
• The type of corticosteroid (prednisone, prednisolone, or methylprednisolone) does not affect survival benefit 4
• Maximum benefit is observed in patients with MELD scores between 25-39, with 21-30% survival benefit 4
• No benefit is seen in patients with MELD >51 4

Step 3: Assess Response at Day 7 Using Lille Score

The Lille score is calculated using age, albumin at day 0, change in bilirubin from day 0 to day 7, renal function, bilirubin at day 0, and prothrombin time 2, 3

Treatment decisions based on Lille score: 3

• Lille <0.45 (complete responder): Continue corticosteroids for full 28 days (85% 6-month survival)
• Lille 0.45-0.56 (partial responder): Consider stopping on case-by-case basis (79.4% 28-day survival)
• Lille ≥0.56 (null responder): Stop corticosteroids immediately (53.3% 28-day survival, no benefit from continued therapy, only increased infection risk)

Alternative Therapy for Contraindications to Corticosteroids

• N-acetylcysteine combined with corticosteroids may improve short-term survival (weak recommendation) 2
• Do not use pentoxifylline—multiple large trials show no survival benefit and no reduction in hepatorenal syndrome 3

Monitoring During Treatment

Infection Surveillance

• Infection develops in 25% of patients during the first month of corticosteroid treatment 3
• Repeat infection screening (blood, urine, ascites cultures) if any clinical deterioration occurs 2, 3
• Development of multi-organ failure, usually due to infections, is associated with very high mortality 1, 2

Prognostic Assessment

• Combine Lille and MELD scores for optimal prediction of short and medium-term mortality risk 2, 5, 3

Liver Transplantation Consideration

• Patients with severe alcoholic hepatitis (particularly MELD >26) who are null responders to corticosteroids (Lille ≥0.45) should be referred for early liver transplantation evaluation 1, 3
• Selection criteria include first episode of severe alcoholic hepatitis, good insight into alcohol use disorder, and strong social support 1, 6, 7
• The traditional 6-month abstinence requirement cannot be met by these critically ill patients, but emerging data support transplantation in carefully selected cases 6, 7

Long-Term Outcomes and Relapse Prevention

• Medical treatment responders have 5-year survival rates of approximately 80% if abstinence is maintained, dropping to approximately 50% with alcohol relapse 2, 5
• Corticosteroids improve only short-term (28-day) survival with no significant benefit at 3 months and beyond 2, 5, 7, 8
• Systematically offer addiction treatment including naltrexone, acamprosate, or baclofen (for patients with cirrhosis) combined with counseling 1, 5

Critical Pitfalls to Avoid

• Never continue corticosteroids beyond day 7 in non-responders (Lille ≥0.56)—this exposes patients to infection risk without any survival benefit 3
• Never use iodinated contrast dye liberally for imaging, as it increases acute kidney injury risk 1
• Never rely on parenteral nutrition alone—enteral feeding is essential for adequate recovery 1
• Never prescribe pentoxifylline as an alternative or adjunct to corticosteroids 3
• Never recommend cutting back on alcohol rather than complete abstinence—there is significant risk of recidivism with this approach, and no safe amount of alcohol consumption exists after alcoholic hepatitis 1