What is the Lille score in patients with severe alcoholic hepatitis?

What is the Lille Score?

The Lille score is a dynamic prognostic model calculated on day 7 of corticosteroid therapy in patients with severe alcoholic hepatitis to identify treatment non-responders and guide decisions about continuing or stopping corticosteroids. 1

Purpose and Clinical Context

The Lille score addresses a critical clinical need: early identification of patients with severe alcoholic hepatitis who are not responding to corticosteroid therapy and require alternative management strategies. 1, 2 Unlike static prognostic scores (Maddrey, MELD, ABIC) that assess baseline severity, the Lille score is a dynamic model that incorporates both baseline patient characteristics and the change in bilirubin during the first week of treatment. 1, 2

Formula Components

The Lille score integrates six variables measured at treatment initiation and day 7: 1, 3

• Age (in years) - coefficient of -0.101 4, 3
• Albumin on day 0 (in g/L) - coefficient of +0.147 4, 3
• Bilirubin on day 0 (in μmol/L) - coefficient of -0.0065 4, 3
• Prothrombin time (in seconds) - coefficient of -0.0096 4, 3
• Renal insufficiency - coded as 0 if creatinine <1.3 mg/dL or 1 if ≥1.3 mg/dL, coefficient of -0.206 4, 3
• Evolution in bilirubin level - calculated as (bilirubin day 0 minus bilirubin day 7 in μmol/L), coefficient of +0.0165 4, 3

The calculation follows this formula: R = 3.19 – 0.101×age + 0.147×albumin day 0 + 0.0165×(bilirubin day 0 – bilirubin day 7) – 0.206×renal insufficiency – 0.0065×bilirubin day 0 – 0.0096×prothrombin time, then Lille score = exp(–R) / [1 + exp(–R)]. 3

Timing of Calculation

• Standard timing: Calculate on day 7 of corticosteroid treatment 1, 3
• Alternative timing: Day 4 calculation shows similar prognostic performance but requires further validation 1, 5
• In clinical practice, most patients are not discharged before day 7, making the day 7 calculation practical 1

Score Interpretation and Mortality Prediction

The Lille score stratifies patients into response categories with dramatically different survival outcomes: 1, 3

• Complete responders (Lille ≤0.16): 91.1% 28-day survival 3
• Partial responders (Lille 0.16-0.56): 79.4% 28-day survival 3
• Null responders (Lille ≥0.56): 53.3% 28-day survival 3

The critical threshold is Lille ≥0.45, which identifies non-responders with only 20-30% 6-month survival compared to 70-80% for responders (score <0.45). 1, 2 This cutoff identifies approximately 75% of observed deaths. 2

Clinical Decision-Making Algorithm

For Lille score ≥0.56 (null responders): 1, 3

• Stop corticosteroids immediately - therapy is as effective as placebo in this group 1
• Consider liver transplantation as primary rescue option 1
• Increased infection risk makes continued steroids harmful 1

For Lille score 0.45-0.56 (partial responders): 1

• Decision to continue corticosteroids must be made case-by-case 1
• Weigh infection risk against potential marginal benefit 1

For Lille score <0.45 (responders): 1

• Continue corticosteroid therapy 1
• Expected 6-month survival 70-80% 1

Prognostic Performance

The Lille model demonstrates superior prognostic accuracy compared to static models: 2

• Lille model AUROC: 0.89 ± 0.02 in development cohort, 0.85 ± 0.04 in validation cohort 2
• Child-Pugh AUROC: 0.62 ± 0.04 (p < 0.00001 vs. Lille) 2
• Maddrey AUROC: 0.66 ± 0.04 (p < 0.00001 vs. Lille) 2
• MELD AUROC: 0.72 ± 0.05 (p = 0.01 vs. Lille) 2

Integration with Other Scores

Combining Lille with baseline severity scores provides optimal prognostication: 1, 6

• The MELD + Lille combination is superior to Maddrey + Lille or ABIC + Lille for predicting patient survival 6
• For example, with baseline MELD 21, a patient with Lille 0.45 has 1.9-fold higher death risk than one with Lille 0.16 (23.7% vs 12.5% mortality) 6
• This combined approach is valuable for selecting candidates for fast-track liver transplantation 1

Critical Pitfalls to Avoid

• Do not ignore renal function - renal insufficiency is a critical component and predictor of poor outcomes 4
• Do not continue steroids in null responders (Lille ≥0.56) - this increases infection risk without benefit 1
• Do not use Lille score at baseline - it requires day 7 bilirubin change to be valid 1
• Do not confuse Lille score with static prognostic scores - Lille assesses treatment response, not baseline severity 2