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...

Individual susceptibility to ALD is substantially driven by IM. It may, therefore, be possible to prevent and manage ALD by IM manipulation.

Analysis of individual data from five RCTs showed that corticosteroids significantly improve 28-day survival in patients with severe alcoholic hepatitis. The survival benefit is mainly observed in patients classified as responders by the Lille model.

PATIENTS AND METHODSThough the hepatotoxicity of ethanol has been established, only 8% to 20% of chronic alcoholics develop cirBetween January of 1982 and May of 1995, a total of 2,848 patients rhosis. The aim of this study was to assess whether being were admitted to the Hepatogastroenterology Unit of the Antoine overweight is a risk factor for alcoholic liver disease. Béclère Hospital in Clamart, France, for alcoholism or alcoholic liver One thousand six hundred four alcoholic patients were disease. To be included in the study, patients must have drunk at studied. According to the liver biopsies, 194 patients had least 50 g of alcohol per day over the previous year. We used only a normal liver; 402 had steatosis without fibrosis; 281 the data that were recorded during the first admissions in our unit. presented with fibrosis, with or without steatosis; 119 From these 2,848 patients, 1,244 patients were excluded, including 596 on whom no liver biopsy was performed and for whom cirrhosis presented with acute alcoholic hepatitis (AAH) without was not clinically obvious, and 313 because of missing data. Fortycirrhosis; 232 indicated cirrhosis without AAH; and 179 one patients were excluded because of the presence of hepatitis B presented with cirrhosis with AAH. One hundred ninetysurface antigen; 289 were excluded because of the presence of antiseven patients had clinically obvious cirrhosis. In the bodies to hepatitis C virus; and 5 patients were excluded because of study, five variables were studied as risk factors: age, the presence of hepatitis B surface antigen and antibodies to hepatisex, daily consumption of alcohol during the previous 5 tis C virus. In fact, hepatitis B virus markers were prospectively and years, the total duration of alcohol abuse, and tendency systematically recorded in all patients. Serum antibodies against to be overweight (body mass index [BMI] ¢ 25 in women hepatitis C virus were also assessed in all patients when serum and ¢ 27 in men). The BMI was calculated according to markers for hepatitis C virus infection became available. 5 Hepatitis C virus antibodies were tested retrospectively with a first-generathe minimum weight over the 10 previous years. In the tion, enzyme-linked immunosorbent assay system (Ortho Diagnostic first stepwise logistic regression analysis, age, being System, Raritan, NJ) from January 1982 to May 1991, afterward, overweight for at least 10 years, being of the female sex, they were tested prospectively with second-and third-generation and the total duration of alcohol abuse were indepenenzyme-linked immunosorbent assay systems. dently correlated with the presence of cirrhosis. In the One thousand six hundred and four patients were included in the second analysis, female sex being overweight were the study of which 608 had cirrhosis. This was histologically proven in 411 two independent risk factors of AAH. In the third analy-patients and was clinically obvious in the other 197 patients, who had sis, being overweight for at least 10 years was the only a posi...

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for the Foie-Alcool group of the Association Française pour l'Etude du Foie (AFEF)** Tumor necrosis factor-␣ (TNF-␣) may contribute to the progression of acute alcoholic hepatitis (AAH). The aim of this study was to evaluate the efficacy of an association of infliximab and prednisolone at reducing the 2-month mortality rate among patients with severe AAH. Patients with severe AAH (Maddrey score >32) were randomly assigned to group A receiving intravenous infusions of infliximab (10 mg/kg) in weeks 0, 2, and 4; or group B receiving a placebo at the same times. All patients received prednisolone (40 mg/day) for 28 days. Blood neutrophil functional capacities were monitored over 28 days. After randomization of 36 patients, seven patients from group A and three from group B died within 2 months. The probability of being dead at 2 months was higher (not significant [NS]) in group A (39% ؎ 11%) than in group B (18% ؎ 9%). The study was stopped by the follow-up committee and the sponsor (Assistance Publique-Hôpitaux de Paris). The frequency of severe infections within 2 months was higher in group A than in group B (P < .002). This difference was potentially related to a significantly lower ex vivo stimulation capacity of neutrophils. There were no differences between the two groups in terms of Maddrey scores at any time point. In conclusion, three infusions of 10 mg/kg of infliximab in association with prednisolone may be harmful in patients with severe AAH because of the high prevalence of severe infections.

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Background: FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC).