Main drivers of outcome differ between short term and long term in severe alcoholic hepatitis: A prospective study

Autor: Alain Duhamel, Alexandre Louvet, Elise Lemaître, Benjamin Rolland, Julien Labreuche, V. Canva-Delcambre, Sébastien Dharancy, Guillaume Lassailly, Florent Artru, Alexis Bouthors, Pierre Saffers, Philippe Mathurin, Julien Lollivier
Přispěvatelé: Service des Maladies de l'Appareil Digestif et de la Nutrition [CHRU Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Rok vydání: 2016
Předmět:
Zdroj: Hepatology
Hepatology, Wiley-Blackwell, 2017, Hepatology (Baltimore, Md.), 66 (5), pp.1464-1473. ⟨10.1002/hep.29240⟩
Hepatology, 2017, Hepatology (Baltimore, Md.), 66 (5), pp.1464-1473. ⟨10.1002/hep.29240⟩
ISSN: 1527-3350
0270-9139
DOI: 10.1002/hep.29240⟩
Popis: Understanding the mechanisms of outcome according to the time frame can help optimize the therapeutic development in severe alcoholic hepatitis. We assessed short-term and long-term survival in severe alcoholic hepatitis based on baseline disease severity, extent of therapeutic improvement, long-term influence of alcohol relapse, and their interaction. Data and alcohol consumption were prospectively recorded in 398 patients treated with corticosteroids in the short term (from corticosteroid initiation to 6 months) and long term (from 6 months to maximum follow-up time). Cumulative incidence rate of first alcohol relapse was 25.2%, 33.7%, and 35.2% at 1, 3, and 5 years, respectively. Alcohol relapse (≥30 g/day) was not associated with mortality (P = 0.24) during the short-term period (1,606 patient-months at risk), but the Lille (P 0.0001) and Model for End-Stage Liver Disease (P 0.0001) scores were independent prognostic factors. In patients who were alive at 6 months (median follow-up, 42 months; interquartile range 11-88), corresponding to 10,413 patient-months at risk, alcohol consumption (≥30 g/day) was associated with mortality (hazard ratio, 3.9; P 0.0001). Additional analysis with abstinent patients as a reference showed a dose effect of alcohol on the hazard ratio of death: 2.36 (P = 0.052) for 1-29 g/day, 3.2 (P = 0.003) for 30-49 g/day, 3.51 (P 0.0001) for 50-99 g/day, and 5.61 (P 0.0001) for ≥ 100 g/day. The baseline Model for End-Stage Liver Disease score was not predictive of long-term outcome, while Lille score (P = 0.02) and alcohol relapse (P 0.0001) were independent prognostic factors.This study shows that new therapeutic development for severe alcoholic hepatitis must target liver injury in the short term and alcohol consumption in the long term; thus, health agencies can endorse future study designs adapted to the time frame of factors influencing mortality; with this in mind, drug-targeting mechanisms involved in liver injury should only be tested for the short-term period. (Hepatology 2017;66:1464-1473).
Databáze: OpenAIRE
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