L’astinenza da alcol è il principale fattore prognostico positivo nella AH severa

Main drivers of outcome differ between short and long-term in severe alcoholic hepatitis: A prospective study.Louvet A, Labreuche J, Artru F, Bouthors A, Rolland B, Saffers P, Lollivier J, Lemaître E, Dharancy S, Lassailly G, Canva-Delcambre V, Duhamel A, Mathurin P. Hepatology. 2017 Apr 29. [Epub ahead of print]

Understanding the mechanisms of outcome according to the time frame can help optimize the therapeutic development in severe alcoholic hepatitis (AH).OBJECTIVE:to assess short-term and long-term survival in severe AH based on baseline disease severity, extent of therapeutic improvement, long-term influence of alcohol relapse and their interaction.

DESIGN:Data and alcohol consumption were prospectively recorded in 398 patients treated with corticosteroids at short (from corticosteroid initiation to 6 months) and long term (from 6 months to maximum follow-up time).RESULTS:Cumulative incidence rate of first alcohol relapse was 25.2%, 33.7% and 35.2% at 1, 3 and 5 years, respectively. Alcohol relapse (≥30g/day) was not associated with mortality (p=0.24) during the short-term period (1606 patients-months at risk) but the Lille (p<0.0001) and MELD (p<0.0001) scores were independent prognostic factors. In patients who were alive at 6 months (median follow-up: 42 months, IQR11-88), corresponding to 10413 patients-months at risk, alcohol consumption (≥30g/day) was associated with mortality (HR 3.9, p<0.0001). Additional analysis with abstinent patients as a reference showed a dose effect of alcohol on the HR of death: 2.36 (p=0.052) for 1-29g/day, 3.2 (p=0.003) for 30-49g/day, 3.51 (p<0.0001) for 50-99g/day and 5.61 (p<0.0001) for ≥100g/day. The baseline MELD score was not predictive of long-term outcome while Lille score (p=0.02) and alcohol relapse (p<0.0001) were independent prognostic factors.CONCLUSION:This study shows that new therapeutic development for severe AH must target liver injury for short term and alcohol consumption for long term. Thus, health agencies can endorse future study design adapted to the time-frame of factors influencing mortality. With this in mind, drugs targeting mechanisms involved in liver injury should only be tested for the short-term period. Leggi l'articolo

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