[en] Background: Early liver transplantation for severe alcohol-related hepatitis is an emerging treatment option. We aimed to assess the risk of alcohol relapse 2 years after early liver transplantation for alcohol-related hepatitis compared with liver transplantation for alcohol-related cirrhosis after at least 6 months of abstinence. Methods: We conducted a multicentre, non-randomised, non-inferiority, controlled study in 19 French and Belgian hospitals. All participants were aged 18 years or older. There were three groups of patients recruited prospectively: patients with severe alcohol-related hepatitis who did not respond to medical treatment and were eligible for early liver transplantation according to a new selection scoring system based on social and addiction items that can be quantified in points (early transplantation group); patients with alcohol-related cirrhosis listed for liver transplantation after at least 6 months of abstinence (standard transplantation group); patients with severe alcohol-related hepatitis not responding to medical treatment not eligible for early liver transplantation according to the selection score (not eligible for early transplantation group), this group did not enter any further liver transplantation processes. We also defined a historical control group of patients with severe alcohol-related hepatitis unresponsive to medical therapy and non-transplanted. The primary outcome was the non-inferiority of 2-year rate of alcohol relapse after transplantation in the early transplantation group compared with the standard transplantation group using the alcohol timeline follow back (TLFB) method and a prespecified non-inferiority margin of 10%. Secondary outcomes were the pattern of alcohol relapse, 2-year survival rate post-transplant in the early transplantation group compared with the standard transplantation group, and 2-year overall survival in the early transplantation group compared with patients in the not eligible for early transplantation group and historical controls. This trial is registered with ClinicalTrials.gov, NCT01756794. Findings: Between Dec 5, 2012, and June 30, 2016, we included 149 patients with severe alcohol-related hepatitis: 102 in the early transplantation group and 47 in the not eligible for early transplantation group. 129 patients were included in the standard transplantation group. 68 patients in the early transplantation group and 93 patients in the standard transplantation group received a liver transplant. 23 (34%) patients relapsed in the early transplantation group, and 23 (25%) patients relapsed in the standard transplantation group; therefore, the non-inferiority of early transplantation versus standard transplantation was not demonstrated (absolute difference 9·1% [95% CI –∞ to 21·1]; p=0·45). The 2-year rate of high alcohol intake was greater in the early transplantation group than the standard transplantation group (absolute difference 16·7% [95% CI 5·8–27·6]) The time spent drinking alcohol was not different between the two groups (standardised difference 0·24 [95% CI −0·07 to 0·55]), but the time spent drinking a large quantity of alcohol was higher in the early transplantation group than the standard transplantation group (standardised difference 0·50 [95% CI 0·17–0·82]). 2-year post-transplant survival was similar between the early transplantation group and the standard transplantation group (hazard ratio [HR] 0·87 [95% CI 0·33–2·26]); 2-year overall survival was higher in the early transplantation group than the not eligible for early transplantation group and historical controls (HR 0·27 [95% CI 0·16–0·47] and 0·21 [0·13–0·32]). Interpretation: We cannot conclude non-inferiority in terms of rate of alcohol relapse post-transplant between early liver transplantation and standard transplantation. High alcohol intake is more frequent after early liver transplantation. This prospective controlled study confirms the important survival benefit related to early liver transplantation for severe alcohol-related hepatitis; and this study provides objective data on survival and alcohol relapse to tailor the management of patients with severe alcohol-related hepatitis. Funding: The present study has been granted by the French Ministry of Health—Programme Hospitalier de Recherche Clinique 2010.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Louvet, Alexandre; Services des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Lille, Lille, France
Labreuche, Julien; Department of Biostatistics, Centre Hospitalier Universitaire de Lille, Lille, France
Moreno, Christophe; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Vanlemmens, Claire; Service d'hépatologie, Hôpital Jean-Minjoz, Centre Hospitalier Universitaire de Besançon, Besançon, France
Moirand, Romain; Université de Rennes, INRAE, INSERM, Centre Hospitalier Universitaire Rennes, Unité Nutrition Metabolisms and Cancer, Service des Maladies du Foie et UF Addictologie Rennes, France
Féray, Cyrille; Centre hépatobiliaire, Hôpital Paul-Brousse Assistance Publique Hôpitaux de Paris, Université Paris-Saclay, Paris, France
Dumortier, Jérôme; Fédération des spécialités digestives, Hôpital Edouard-Herriot, Hospices Civils de Lyon et Université de Lyon, Lyon, France
Pageaux, Georges-Philippe; Département d'hépato-gastroentérologie et de transplantation hépatique, Centre Hospitalier Universitaire de Montpellier, Montpellier, France
Bureau, Christophe; Service d'Hépatologie, Hôpital Rangueil, Centre Hospitalier Universitaire de Toulouse, Toulouse, France
Chermak, Faïza; Service d'hépato-gastroentérologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Duvoux, Christophe; Service d'hépatologie, Hôpital Henri-Mondor Assistance Publique Hôpitaux de Paris, Paris, France
Thabut, Dominique; Service d'hépato-gastroentérologie, Sorbonne Université, Hôpital Pitié-Salpêtrière Assistance Publique Hôpitaux de Paris, Paris, France
Leroy, Vincent; Clinique d'Hépato-gastroentérologie, Centre Hospitalier Universitaire de Grenoble, Grenoble, France
Carbonell, Nicolas; Service d'hépatologie, Hôpital Saint-Antoine Assistance Publique Hôpitaux de Paris, Paris, France
Rolland, Benjamin; Service Universitaire d'Addictologie de Lyon, Centre Hospitalier Le Vinatier, Hospices Civils de Lyon et Université de Lyon, Lyon, France
Salamé, Ephrem; Service de chirurgie hépatique et transplantation, Centre Hospitalier Universitaire de Tours, Tours, France
Anty, Rodolphe; Université Côte d'Azur, Centre Hospitalier Universitaire, Inserm U1065, C3M, Nice, France
Gournay, Jérôme; Service d'hépato-gastroentérologie, Centre Hospitalier Universitaire de Nantes, Nantes, France
DELWAIDE, Jean ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive
Silvain, Christine; Service d'hépato-gastroentérologie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France
Lucidi, Valerio; Liver Transplant Unit, Department of Abdominal Surgery, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Lassailly, Guillaume; Services des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Lille, Lille, France
Dharancy, Sébastien; Services des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Lille, Lille, France
Nguyen-Khac, Eric; Service d'hépato-gastroentérologie, Centre Hospitalier Universitaire d'Amiens, Amiens, France
Samuel, Didier; Centre hépatobiliaire, Hôpital Paul-Brousse Assistance Publique Hôpitaux de Paris, Université Paris-Saclay, Paris, France
Duhamel, Alain; Department of Biostatistics, Centre Hospitalier Universitaire de Lille, Lille, France
Mathurin, Philippe; Services des maladies de l'appareil digestif, Centre Hospitalier Universitaire de Lille, Lille, France
Berthot, Christophe
Claudet, Sylvie
Doussot, Alexandre
Gérardin, Caroline
Muel, Emilie
Hiriart, Jean-Baptiste
Degré, Delphine
Gustot, Thierry
Bonadona, Agnès
Bordy, Laure
Hilleret, Marie-Noelle
DETRY, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
HONORE, Pierre ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
MEURISSE, Nicolas ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chirurgie abdo, sénologique, endocrine et de transplantation
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