Elafibranor, an Agonist of the Peroxisome Proliferator−Activated Receptor−α and −δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening

作者：Vlad Ratziu, Stephen A. Harrison, Sven Francque, Pierre Bédossa, Philippe Lehert, Lawrence Serfaty, Manuel Romero‐Gómez, Jérôme Boursier, Manal F. Abdelmalek, Steve Caldwell, Joost P.H. Drenth, Quentin M. Anstee, Dean W. Hum, Rémy Hanf, A. Roudot, S. Megnien, Bart Staels, Arun J. Sanyal, Philippe Mathurin, Jérôme Gournay, Éric Nguyen-Khac, Victor de Lédinghen, Dominique Larrey, Albert Tran, Marc Bourlière, M. Maynard-Muet, Tarik Asselah, Jean Henrion, Frederik Nevens, David Cassiman, Anja Geerts, Christophe Moreno, Ulrich Beuers, Peter R. Galle, U. Spengler, Elisabetta Bugianesi, Antonio Craxı̀, M. Angélico, Silvia Fargion, M Voiculescu, Liliana Gheorghe, Liliana Preoțescu, Juan Caballería, Raúl J. Andrade, Javier Crespo, J.L. Callera, Aftab Ala, Guruprasad P. Aithal, George Abouda, Velimir A. Luketic, Mao-Yu Huang, Stuart C. Gordon, Paul J. Pockros, Fred Poordad, Nathan J. Shores, Martin Moehlen, Kiran Bambha, Virginia Clark, Sanjaya K. Satapathy, Samir Parekh, R.K. Reddy, Muhammad Y. Sheikh, Gyöngyi Szabó, John M. Vierling, Timothy E. Foster, Guillermo E. Umpierrez, Chih‐Jen Chang, Terry Box, Juan F. Gallegos‐Orozco · 发表于：Gastroenterology · 年份：2016 · DOI：10.1053/j.gastro.2016.01.038 · 被引用次数：1025 · 研究领域：Liver Disease Diagnosis and Treatment、Liver Disease and Transplantation、Liver physiology and pathology

BACKGROUND & AIMS: Elafibranor is an agonist of the peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor-δ. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. We assessed the safety and efficacy of elafibranor in an international, randomized, double-blind placebo-controlled trial of patients with nonalcoholic steatohepatitis (NASH). METHODS: Patients with NASH without cirrhosis were randomly assigned to groups given elafibranor 80 mg (n = 93), elafibranor 120 mg (n = 91), or placebo (n = 92) each day for 52 weeks at sites in Europe and the United States. Clinical and laboratory evaluations were performed every 2 months during this 1-year period. Liver biopsies were then collected and patients were assessed 3 months later. The primary outcome was resolution of NASH without fibrosis worsening, using protocol-defined and modified definitions. Data from the groups given the different doses of elafibranor were compared with those from the placebo group using step-down logistic regression, adjusting for baseline nonalcoholic fatty liver disease activity score. RESULTS: In intention-to-treat analysis, there was no significant difference between the elafibranor and placebo groups in the protocol-defined primary outcome. However, NASH resolved without fibrosis worsening in a higher proportion of patients in the 120-mg elafibranor group vs the placebo group (19% vs 12%; odds ratio = 2.31; ...