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Case definitions for inclusion and analysis of endpoints in clinical trials for nonalcoholic steatohepatitis through the lens of regulatory science

Lookup NU author(s): Professor Quentin AnsteeORCiD



This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


© 2017 The Authors. Hepatology published by Wiley Periodicals, Inc. on behalf of American Association for the Study of Liver Diseases. Nonalcoholic steatohepatitis (NASH) is an important cause of liver-related morbidity and mortality. There are no approved therapies, and the results of clinical trials have been difficult to compare due to inconsistent definitions of relevant disease parameters in patients with NASH. The natural course of the disease has not been rigorously characterized, particularly with respect to the contributions of underlying obesity, type 2 diabetes, and other comorbidities and the treatments provided for these comorbidities. Efforts to perform analyses of pooled data are limited by heterogeneous case definitions used across studies to define disease states. There remains a major unmet need in the field to develop standardized definitions for populations for interventional trials. Such definitions are expected to impact how endpoints for clinical trials are constructed. The Liver Forum is a multistakeholder effort including US and European regulatory agencies, academic investigators, professional and patient representative organizations, and industry to catalyze therapeutic development for NASH by developing potential solutions to barriers to development. The Case Definitions Working Group was established by The Liver Forum to evaluate the validity of case definitions for populations to be included in clinical trials for NASH from a regulatory science perspective. Based on such analyses, specific recommendations are provided noting the strengths and weaknesses of the case definitions along with knowledge gaps that require additional study. (Hepatology 2018;67:2001-2012).

Publication metadata

Author(s): Siddiqui MS, Harrison SA, Abdelmalek MF, Anstee QM, Bedossa P, Castera L, Dimick-Santos L, Friedman SL, Greene K, Kleiner DE, Megnien S, Neuschwander-Tetri BA, Ratziu V, Schabel E, Miller V, Sanyal AJ

Publication type: Article

Publication status: Published

Journal: Hepatology

Year: 2018

Volume: 67

Issue: 5

Pages: 2001-2012

Print publication date: 18/04/2018

Online publication date: 23/10/2017

Acceptance date: 23/10/2017

Date deposited: 04/06/2018

ISSN (print): 0270-9139

ISSN (electronic): 1527-3350

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/hep.29607


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Funder referenceFunder name
National Institutes of Health . Grant Number: RO1 DK 10596
Intramural Research Program of the National Institutes of Health, National Cancer Institute