What is the Lille score (alcoholic hepatitis prognostic tool) formula and how is it used to predict mortality in a patient with impaired health status, potential comorbidities, and a history of alcohol abuse?

Lille Score Formula and Clinical Application

The Lille score is calculated as R = 3.19 – 0.101×[age (years)] + 0.147×[albumin on day 0 (g/L)] + 0.0165×[evolution in bilirubin level (μmol/L)] − 0.206×renal insufficiency − 0.0065×[bilirubin on day 0 (μmol/L)] − 0.0096×[PT (seconds)], with the final Lille score = exp(–R)/[1+exp(–R)], and a score ≥0.45 predicts approximately 75% mortality within 6 months in patients receiving corticosteroid therapy for severe alcoholic hepatitis. 1

Formula Components and Calculation

The Lille model requires the following variables:

• Age in years 1
• Albumin on day 0 in g/L 1
• Bilirubin on day 0 in μmol/L 1
• Prothrombin time in seconds 1
• Renal insufficiency: coded as 0 if creatinine <1.3 mg/dL or 1 if creatinine ≥1.3 mg/dL 1
• Evolution in bilirubin level: calculated as bilirubin on day 0 minus bilirubin on day 7 (in μmol/L) 1

The calculation proceeds in two steps: first calculate R using the formula above, then convert to the final Lille score using the exponential transformation. 1

Clinical Interpretation and Mortality Prediction

Critical Threshold

• Lille score ≥0.45 identifies non-responders to corticosteroid therapy with typically 75% mortality within 6 months 1
• Lille score <0.45 identifies responders with significantly better survival outcomes 2
• A Lille score >0.56 indicates null responders who derive no benefit from continued corticosteroid therapy 2

Timing of Assessment

The Lille score is traditionally calculated after 7 days of corticosteroid therapy to assess treatment response and guide continuation or discontinuation of therapy. 1, 3, 4

Recent evidence demonstrates that Lille scores calculated at day 4 (LM4) perform equivalently to day 7 (LM7), with 90.3% of patients correctly identified as responders or non-responders, allowing earlier treatment decisions and avoidance of prolonged corticosteroid exposure. 5

• Day 3-6 Lille scores (LM3-6) show comparable accuracy to LM7, with area under ROC curves ranging from 0.743 to 0.809 for predicting 90-day mortality 6
• Early Lille assessment (days 3-6) allows discontinuation of ineffective therapy before complications develop 6

Integration with Other Prognostic Models

Combined Scoring Approach

The combination of MELD score with Lille score provides superior prognostic accuracy compared to either model alone, with the MELD+Lille combination achieving the best performance (Akaike information criterion value of 1305) for predicting both 2-month and 6-month mortality. 7

The joint-effect model demonstrates:

• For patients with MELD score of 21, a Lille score of 0.45 confers 1.9-fold higher mortality risk compared to Lille score of 0.16 (23.7% vs 12.5%) 7
• Complete responders (Lille 0.16) with MELD 15-45 have predicted 6-month mortality of 8.5%-49.7%, versus 16.4%-75.2% for non-responders (Lille 0.45) 7

Complementary Static Models

The Lille model functions as an on-treatment dynamic model that complements pre-treatment static models: 1, 3

• mDF score ≥32: identifies severe alcoholic hepatitis requiring treatment consideration 1, 3
• MELD score >21: predicts 20% mortality at 90 days 1
• GAHS ≥9: identifies patients benefiting from corticosteroid therapy with >50% mortality at 28-84 days without treatment 1, 3
• ABIC score: stratifies 90-day mortality into low (<6.71,0% mortality), intermediate (6.71-9.0,30% mortality), and high (>9.0,75% mortality) risk categories 1, 3

Clinical Application Algorithm

Step 1: Initial Assessment (Day 0)

Calculate baseline prognostic scores (mDF, MELD, GAHS, ABIC) to determine disease severity and treatment candidacy. 3, 4

Step 2: Treatment Initiation

For severe alcoholic hepatitis (mDF ≥32 or MELD >20) without contraindications, initiate methylprednisolone 32 mg daily after excluding active infection. 3, 4

Step 3: Early Response Assessment (Day 4-7)

Calculate Lille score at day 4 to identify non-responders early, allowing discontinuation of ineffective corticosteroid therapy before complications develop. 5, 6

• Lille <0.45: Continue corticosteroids for full 28-day course 2
• Lille 0.45-0.56: Consider stopping corticosteroids or switching to pentoxifylline 2
• Lille >0.56: Stop corticosteroids immediately as null responder 2

Step 4: Combined Risk Stratification

Use MELD+Lille combination for optimal mortality prediction and to guide discussions about liver transplantation evaluation. 7

Critical Pitfalls to Avoid

• Do not continue corticosteroids beyond day 7 in patients with Lille score ≥0.45, as this exposes patients to infection risk and other steroid complications without survival benefit 4, 2
• Do not rely on Lille score alone for initial treatment decisions—it is an on-treatment model requiring baseline and day 7 measurements, not a pre-treatment stratification tool 1, 3
• Do not delay Lille calculation until day 7 when day 4 assessment provides equivalent prognostic information and allows earlier treatment modification 5, 6
• Do not ignore renal function in the Lille calculation, as renal insufficiency is a critical component and predictor of poor outcomes 1, 6

Enhanced Prognostic Models

A modified Lille score incorporating neutrophil-lymphocyte ratio (NLR) achieves superior performance (AUC 0.889) compared to Lille score alone (AUC 0.819), potentially identifying additional non-responders who would benefit from early treatment cessation. 8