No abstract

Early liver transplantation can improve survival in patients with a first episode of severe alcoholic hepatitis not responding to medical therapy. (Funded by Société Nationale Française de Gastroentérologie.).

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...