What is the Madrey's discriminant score and how is it used to assess and manage alcoholic hepatitis?

Maddrey's Discriminant Function Score

What It Is and How to Calculate It

The Maddrey Discriminant Function (MDF) is a prognostic scoring system specifically designed to identify severe alcoholic hepatitis requiring immediate treatment, calculated as: MDF = 4.6 × (Patient's PT - Control PT) + Total Bilirubin (mg/dL), with a score ≥32 defining severe disease that mandates consideration of corticosteroid therapy. 1, 2

The formula uses two readily available laboratory values:

• Prothrombin time (PT): The difference between patient and control PT in seconds 1
• Total bilirubin: Measured in mg/dL 1

Clinical Application and Risk Stratification

When to Use MDF

Calculate the MDF score in patients presenting with: 2, 3

• Recent heavy alcohol consumption (>40g/day for women, >50-60g/day for men for >6 months) 2
• Rapid onset of jaundice (bilirubin >3 mg/dL) within 60 days of abstinence 2, 3
• AST elevation 50-400 IU/mL with AST/ALT ratio >1.5 2, 3
• Tender hepatomegaly on examination 2

Interpreting the Score

MDF ≥32 (Severe Disease): 1, 2, 4

• Historically associated with 30-50% one-month mortality 1, 4
• Recent studies show improved outcomes with supportive care (approximately 15-17% mortality) 3
• This threshold mandates consideration of prednisolone 40 mg daily for 28 days 2, 5
• Requires extensive bacteriological examination before initiating corticosteroids 5

MDF <32 (Non-Severe Disease): 2, 3, 6

• Still carries substantial mortality: 10% at 6 months and 20% at 1 year 2, 3
• One study found 16.7% died within 28 days even with MDF <32 6
• Requires close monitoring and aggressive supportive care including nutritional therapy 2

Optimal Threshold Considerations

The traditional cutoff of 32 maximizes both sensitivity (66.7%) and specificity (61.5%) for predicting mortality 6. However, some studies suggest higher thresholds may be more accurate:

• MDF >65 showed excellent discrimination for 30-day mortality 7
• MDF >60 for 90-day mortality 7
• MDF >52.8 corresponded to optimal MELD score of >19 8

Integration with Other Prognostic Scores

Combined Prognostication Strategy

Use both static scores at baseline (MDF and MELD) plus dynamic assessment (Lille score at day 7) for optimal risk stratification rather than relying solely on MDF. 2

MELD Score: 2, 3, 8

• MELD >20-21 indicates severe disease with high 90-day mortality 2
• Performs similarly to MDF for 30-day mortality (C-statistics 0.74-0.83 for MDF vs 0.83-0.86 for MELD) 3
• Superior for capturing renal dysfunction through creatinine incorporation 2
• May be preferred when ascites or encephalopathy complicate assessment 3

Lille Score (Day 7): 2, 5, 9

• Calculate on day 7 after initiating corticosteroid therapy 2, 5
• Lille ≥0.45 identifies non-responders 2, 5
• Lille ≥0.56 indicates null responders requiring discontinuation of steroids 2, 5
• Day-4 Lille score (LM4) may be used instead of day-7 assessment, correctly identifying 90.3% of responders 9

Critical Limitations

When NOT to Use MDF

Do not use MDF as a prognostic tool for chronic liver disease unless acute alcoholic hepatitis is superimposed on the chronic disease. 3

MDF fails to account for: 3

• Degree of hepatic fibrosis or cirrhosis stage
• Ongoing alcohol consumption patterns
• Complications beyond the acute inflammatory episode
• Medium-to-long-term prognosis

For chronic liver disease prognosis, use MELD score instead, which is validated for 90-day mortality prediction and transplant prioritization. 3

Accuracy Concerns

The MDF has notable drawbacks: 1

• Although continuous, interpretation using threshold of 32 converts it to essentially categorical classification
• Once patients exceed threshold of 32, risk is higher but not precisely specified
• Does not capture dynamic changes over time

Management Algorithm Based on MDF

MDF ≥32 (Severe Alcoholic Hepatitis)

1. Perform extensive infection screening before initiating therapy 5
2. Start prednisolone 40 mg daily for 28 days if no contraindications 5
3. Calculate Lille score on day 7 (or day 4 for earlier assessment) 2, 5, 9
   • If Lille ≥0.56: Discontinue corticosteroids 5
   • If Lille ≥0.45: Consider non-responder, evaluate alternative therapy 2
4. Provide aggressive nutritional support with high-calorie, high-protein diet 5, 4
5. Alternative: If contraindications to steroids exist, consider pentoxifylline 400 mg orally three times daily for 4 weeks 5

MDF <32 (Non-Severe Alcoholic Hepatitis)

1. Close monitoring with serial laboratory assessments 2
2. Aggressive supportive care including nutritional therapy 2
3. Alcohol abstinence counseling 2, 5
4. Consider alternative therapies given substantial mortality risk 6

Universal Interventions Regardless of Score

• Complete alcohol abstinence is essential 5, 4
• Nutritional supplements: High-calorie, high-protein diet with vitamin E, C, and thiamine 4
• Liver transplantation consideration for treatment failure cases 4

Common Pitfalls to Avoid

1. Assuming MDF <32 means low risk: These patients still face 10-20% mortality at 6-12 months 2, 3, 6
2. Using MDF for chronic liver disease prognosis: It only predicts short-term (30-day) mortality in acute alcoholic hepatitis 3
3. Relying solely on baseline MDF: Incorporate MELD and Lille scores for comprehensive risk assessment 2
4. Continuing steroids in non-responders: Lille score at day 7 should guide continuation or cessation 2, 5
5. Ignoring infection screening: Must perform before initiating immunosuppressive therapy 5