The Lille model: A new tool for therapeutic strategy in patients with severe alcoholic hepatitis treated with steroids

Abstract

Early identification of patients with severe (discriminant function > 32) alcoholic hepatitis (AH) not responding to corticosteroids is crucial. We generated a specific prognostic model (Lille model) to identify candidates early on for alternative therapies. Three hundred twenty patients with AH prospectively treated by corticosteroids were included in the development cohort and 118 in its validation. Baseline data and a change in bilirubin at day 7 were tested. The model was generated by logistic regression. The model combining six reproducible variables (age, renal insufficiency, albumin, prothrombin time, bilirubin, and evolution of bilirubin at day 7) was highly predictive of death at 6 months (P < 0.000001). The area under the receiver operating characteristic (AUROC) curve of the Lille model was 0.89 ؎ 0.02, higher than the Child-Pugh (0.62 ؎ 0.04, P < 0.00001) or Maddrey scores (0.66 ؎ 0.04, P < 0.00001). In the validation cohort, its AUROC was 0.85 ؎ 0.04, still higher than the other models, including MELD (0.72 ؎ 0.05, P ‫؍‬ 0.01) and Glasgow scores (0.67 ؎ 0.05, P ‫؍‬ 0.0008). Patients above the ideal cutoff of 0.45 showed a marked decrease in 6-month survival as compared with others: 25% ؎ 3.8% versus 85% ؎ 2.5%, P < 0.0001. This cutoff was able to identify approximately 75% of the observed deaths. Conclusion: In the largest cohort to date of patients with severe AH, we demonstrate that the term "nonresponder" can now be extended to patients with a Lille score above 0.45, which corresponds to 40% of cases. Early identification of subjects with substantial risk of death according to the Lille model will improve management of patients suffering from severe AH and will aid in the design of future studies for alternative therapies. (HEPATOLOGY 2007;45:1348-1354 T he treatment of severe forms of alcoholic hepatitis (AH) constitutes a major challenge in management of severe alcoholic liver disease. Before the era of the Maddrey function (DF), 1,2 clinicians faced substantial difficulties in identifying subgroups of patients with high risk of death over a short term; as a consequence, survival of untreated patients enrolled in randomized controlled trials (RCTs) ranged from 0 to 81%. 3 Since the use of DF (DF Ն 32) in several RCTs, 1,4-6 spontaneous 2-month survival has been approximately 50%. The DF clearly demonstrates the tremendous progress provided by elaborating specific prognostic functions for AH. The advantage of accurate models has been confirmed by the growing importance of the MELD score in the selection of candidates for liver transplantation. [7][8][9] In patients with DF Ն 32, several RCTs and a recent meta-analysis showed that corticosteroids improve shortterm survival. 1,5,10-14 However, novel strategies or molecules are required, in light of the fact that approximately 40% of patients die at 6 months. 15 Therefore, improvement in the prediction of mortality in severe AH is warranted. However, we lack evidence supporting the higher efficacy of new models such as MELD and Glasgow scores compa...

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

“…The parallel reduction of alkaline phosphatase in the ELAD group versus an increase in the control group may suggest bile flow can improve while on ELAD. Although the response measured by the Lille score, the most validated measure for therapy response in AH,19 was significantly better in ELAD, it did not translate into a successful OS benefit, which the authors interpret as a consequence of the worsening of the outcome in nonresponders in the ELAD arm. Similarly, patients with high MELD scores and of older age had worse outcomes, diluting a potential survival benefit indicated by more Lille responders.…”

Baseline urine metabolic phenotype in patients with severe alcoholic hepatitis and its association with outcome

“…Patients with SAH seen between 2013 and 2015 at the Department of Hepatology, Institute of Liver and Biliary Science, New Delhi, India, and confirmed to have MDF ≥32, recent onset of jaundice, chronic alcohol abuse, and liver biochemistry and histologic features of SAH (n = 180) were screened for corticosteroid therapy 6. All 180 patients underwent transjugular liver biopsy, and a minimum of 10 portal spaces were analyzed before characterization of a patient as SAH.…”

“…Patients were characterized as responders (Rs) or nonresponders (NRs) at day 7 using the Lille score 6. At baseline, none of the enrolled patients with SAH documented high serum creatinine level, suggesting normal functioning of the kidneys.…”

“…It is important to identify patients with SAH at a high risk of mortality before considering specific therapies. Corticosteroid therapy, although controversial, remains the only option to improve the morbidity and short‐term mortality in SAH 2, 4, 5, 6, 7, 8, 9. While the precise mechanisms of action of steroids in SAH are unknown, inhibition of inflammatory reactions and immune‐mediated hepatic destruction play a dominant role 8.…”

“…However, the anti‐anabolic effects of steroids may suppress hepatic regeneration and healing 10. Corticosteroid therapy can prove deleterious in patients with clinical manifestations similar to patients with SAH (10%‐30%) 6. Further, continuing corticosteroids in the nonresponsive patients could result in predisposition to secondary bacterial infections, spontaneous bacterial peritonitis, and increased mortality 11.…”