Management of Severe Alcoholic Hepatitis
For a patient with severe alcoholic hepatitis (Maddrey's discriminant function ≥32 or MELD ≥20), you must first exclude active infection through comprehensive screening, then initiate prednisolone 40 mg daily for 28 days if no contraindications exist, enforce absolute alcohol abstinence, and provide aggressive nutritional support with 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day. 1, 2
Immediate Severity Assessment and Risk Stratification
Calculate both the Maddrey Discriminant Function (MDF ≥32) and MELD score (>20) immediately, as these thresholds identify patients with 40-50% 90-day mortality without treatment and determine eligibility for corticosteroid therapy. 1, 2
An MDF ≥32 predicts approximately 30-40% mortality within 6 months and is the most widely validated trigger for initiating specific medical therapy. 3, 4
MELD >20 independently confirms severe disease and warrants consideration of corticosteroids, with MELD >21 being an alternative threshold used in some protocols. 1, 5
Mandatory Pre-Treatment Infection Screening
Before initiating any corticosteroid therapy, you must definitively exclude active infection, as 20-30% of severe alcoholic hepatitis patients have concurrent infections that drive multi-organ failure and mortality. 1, 2
Required screening includes:
- Blood cultures (obtain immediately, regardless of fever presence) 1, 2
- Urinalysis with urine culture 1, 2
- Chest radiograph to exclude pneumonia 2
- Diagnostic paracentesis with ascitic fluid culture if any ascites is present 1, 2
- Screen for hepatitis B, tuberculosis, and HIV when risk factors exist 1, 2
- Rule out active gastrointestinal bleeding 1, 2
Active infection, uncontrolled GI bleeding, acute pancreatitis, and renal failure (creatinine >2.5 mg/dL) are absolute contraindications to corticosteroids. 1, 2
Corticosteroid Therapy Protocol
If MDF ≥32 or MELD >20 AND all contraindications are excluded, initiate prednisolone 40 mg orally once daily (or methylprednisolone 32 mg IV if oral intake impossible) for a full 28-day course. 1, 2
Corticosteroids provide modest survival benefit at 28 days (84.6% survival with steroids versus 65% with placebo, representing a 30% relative risk reduction and number needed to treat of 5), but no benefit beyond 28 days. 1, 2
On day 7 of treatment, calculate the Lille score to assess response: 1, 2
- Lille <0.45: Continue the full 28-day course; expected 6-month survival approximately 85%
- Lille ≥0.45: Discontinue steroids immediately (non-responders gain no survival benefit and face higher infection risk)
- Lille ≥0.56: Definite null responders with only 53% 28-day survival; steroid cessation is mandatory
After completing 28 days, either stop abruptly or taper over 2 weeks; there is no consensus on the optimal approach. 2
Absolute Alcohol Abstinence (The Most Critical Intervention)
Complete and permanent cessation of all alcohol is the single most important intervention and cornerstone of management, improving long-term survival from approximately 50% to 80% at 5 years. 1, 6, 7
Continued alcohol use after alcoholic hepatitis results in increased rates of variceal bleeding, ascites, hepatic encephalopathy, hepatocellular carcinoma, and death. 1
Initiate pharmacologic support for abstinence: 6, 7
- Baclofen 10 mg three times daily is first-line, as it is safe and effective even in advanced liver disease without hepatotoxicity (A1 recommendation)
- Acamprosate 666 mg three times daily is an alternative, as it has no hepatic metabolism and no reported hepatotoxicity
- Naltrexone should be avoided due to potential hepatotoxicity in liver disease
- Disulfiram is absolutely contraindicated due to direct hepatotoxic effects
Arrange immediate referral to addiction medicine or a structured alcohol treatment program. 6
Aggressive Nutritional Support
Provide 30-40 kcal/kg/day and 1.2-1.5 g protein/kg/day, preferably via the enteral route, as patients with alcoholic hepatitis are profoundly malnourished and nutritional therapy independently improves survival. 1, 2, 6, 7
Daily caloric intake below 21.5 kcal/kg/day in patients receiving corticosteroids is associated with significantly increased infection rates and 6-month mortality (65.8% versus 33.1%). 1
Enteral nutritional supplements reduce mortality by 36% (hazard ratio 0.64; 95% CI 0.48-0.86). 1
Administer thiamine 500 mg IV three times daily for 3-5 days before any glucose-containing fluids to prevent Wernicke's encephalopathy. 2, 6
Supplement with vitamin B12, folic acid, pyridoxine, vitamin D, and zinc, as most patients are deficient and zinc specifically improves gut mucosal barrier integrity. 1, 7
Provide frequent small meals including nighttime snacks to improve nitrogen balance and prevent catabolism. 7
Prevention and Management of Complications
Renal Protection
Avoid nephrotoxic drugs including NSAIDs, intravenous contrast, aminoglycosides, and use diuretics cautiously, as acute kidney injury is an early manifestation of multi-organ failure and significantly worsens prognosis. 1
Monitor creatinine closely; early AKI should be treated promptly with intravenous albumin and vasoconstrictors. 1
Infection Surveillance
Maintain a low threshold for repeat cultures (blood, urine) and chest radiography if clinical status deteriorates, as infections develop in up to 50% of patients receiving corticosteroids and are the primary driver of mortality. 1, 2, 6
Systemic inflammatory response syndrome (SIRS) is strongly associated with infection, multi-organ failure, and high mortality, requiring multidisciplinary care involving hepatology, critical care, infectious disease, and nephrology. 1
Monitoring for Decompensation
- Watch for hepatic encephalopathy, variceal bleeding, and worsening ascites, which are common decompensation events in this population. 2
Common Pitfalls and Contraindicated Interventions
Do NOT combine pentoxifylline with prednisolone, as large randomized trials show no additional survival benefit. 2
Do NOT start corticosteroids in mild-to-moderate disease (MDF <32, MELD <20), as they provide no benefit and increase infection risk. 6
Do NOT order ERCP, MRI, or MRCP unless there is clear suspicion of biliary obstruction; hepatic findings are intra-hepatic. 2
Pentoxifylline 400 mg three times daily may be considered only in patients with absolute contraindications to corticosteroids, though it is less effective than prednisolone. 1, 2
N-acetylcysteine may be used as an adjunct to prednisolone for modest additional benefit, but not as monotherapy. 2
Liver Transplantation Consideration
Patients with severe alcoholic hepatitis, particularly those with MELD >26, good insight into their alcohol use disorder, and strong social support should be referred for liver transplantation evaluation, as 90-day mortality is extremely high (40-50%) despite optimal medical therapy. 1, 2