Treatment Approach for High Maddrey Discriminant Score in Severe Alcoholic Hepatitis
For patients with a Maddrey discriminant function (MDF) ≥32, prednisolone 40 mg daily for 28 days is the recommended treatment, combined with aggressive nutritional support and complete alcohol abstinence. 1
Defining Severe Disease
A Maddrey discriminant function ≥32 identifies patients with severe alcoholic hepatitis who have a 1-month mortality rate of 20-50% without specific treatment. 2 The formula is: MDF = 4.6 × (Patient's PT - Control PT) + Total Bilirubin (mg/dL). 2
Additional severity markers to assess:
- MELD score >20-21 indicates severe disease with high 90-day mortality risk and should be calculated alongside MDF for comprehensive prognostication. 3, 4
- Patients with MDF >60 or MELD >30 have extremely poor prognosis and may require consideration for urgent liver transplantation rather than standard pharmacotherapy. 2
Primary Treatment: Corticosteroids
Prednisolone 40 mg orally daily for 28 days is the standard regimen for severe alcoholic hepatitis (MDF ≥32). 1 This represents the most widely accepted specific therapy, though recent evidence shows more modest benefits than historical data suggested. 2
Pre-treatment Requirements
Before initiating corticosteroids, perform extensive bacteriological examination to rule out active infection, as corticosteroids are contraindicated in the presence of sepsis. 1 Screen for:
- Blood cultures
- Urine cultures
- Ascitic fluid analysis (if ascites present)
- Chest imaging for pneumonia 2
Monitoring Treatment Response: The Lille Score
Calculate the Lille score on day 7 of corticosteroid therapy to identify responders versus non-responders. 3, 1 This dynamic assessment is critical:
- Lille score <0.45: Treatment responder—continue corticosteroids for full 28-day course 1
- Lille score ≥0.45: Non-responder—consider stopping therapy 1
- Lille score ≥0.56: Null responder—discontinue corticosteroids as continued treatment provides no benefit 1
The Lille score incorporates change in bilirubin from day 0 to day 7, along with age, creatinine, albumin, and prothrombin time. 2 The combination of baseline MELD/MDF scores with day 7 Lille score provides optimal risk stratification rather than relying on MDF alone. 3
Alternative Treatment: Pentoxifylline
For patients with contraindications to corticosteroids (active infection, gastrointestinal bleeding, renal failure), pentoxifylline 400 mg orally three times daily for 4 weeks can be considered. 1, 5 This is particularly relevant for patients with hepatorenal syndrome or severe infections. 5
However, the evidence for pentoxifylline is weaker than for corticosteroids, and recent large trials (STOPAH) showed no significant mortality benefit. 6
Essential Supportive Care
Nutritional Therapy
Aggressive nutritional support is mandatory alongside any specific medical treatment. 1 Patients with severe alcoholic hepatitis are typically severely malnourished:
- Provide enteral nutrition with high-calorie, high-protein diet (1.2-1.5 g/kg protein daily) 5
- Supplement with thiamine, folate, and multivitamins 5
- Consider nasogastric or nasojejunal feeding if oral intake is inadequate 2
Alcohol Abstinence
Complete and permanent alcohol abstinence is essential and should be strongly emphasized, as continued drinking is the primary determinant of long-term mortality beyond one year. 2, 1
Important Clinical Pitfalls
Do not assume patients with MDF <32 are safe. Even "moderate" alcoholic hepatitis carries 10% mortality at 6 months and 20% at 1 year, requiring close monitoring and aggressive supportive care. 3 These patients were historically excluded from trials but represent a significant at-risk population. 2
Recent trials show lower mortality rates than historical data (17% vs 35% at 28 days) due to improvements in best supportive care, making direct comparisons with older literature difficult. 2 This emphasizes that optimal supportive care—nutrition, infection management, and alcohol cessation—may be as important as specific pharmacotherapy.
Infections are common and increase mortality. The presence of systemic inflammatory response syndrome (SIRS) without infection is frequent in alcoholic hepatitis, but true bacterial infections must be identified and treated aggressively. 2
Prognosis and Transplantation
Even with optimal treatment, mortality remains substantial: 6-month survival is approximately 70-80% in corticosteroid responders. 1 For non-responders to medical therapy with MDF >60 or MELD >30, early liver transplantation should be considered in carefully selected patients, though this remains controversial and requires strict selection criteria including demonstrated commitment to abstinence. 6