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Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum.

Publication ,  Journal Article
Cheung, A; Neuschwander-Tetri, BA; Kleiner, DE; Schabel, E; Rinella, M; Harrison, S; Ratziu, V; Sanyal, AJ; Loomba, R; Jeannin Megnien, S ...
Published in: Hepatology
November 2019

Identifying effective therapies for nonalcoholic steatohepatitis (NASH) with fibrosis is a pressing challenge, with 1%-2% of the population in developed nations at risk of developing NASH cirrhosis and its complications. The design of NASH clinical therapeutic trials is hampered by the long period of minimally symptomatic disease that typically precedes the development of decompensated cirrhosis and the accompanying uncertainties regarding the best precirrhotic trial endpoints that reliably reflect a subsequent reduction in liver-related morbidity and mortality. The Liver Forum is a multistakeholder organization comprised of academic, industry, and regulatory experts working from a regulatory science perspective to identify barriers, prioritize research, and identify solutions to accelerate therapeutic development for NASH. Past work of The Liver Forum has focused on recommendations for disease definitions and baseline parameters to be implemented in clinical trials that are designed to assess disease status and prevent progression to cirrhosis, liver transplantation, hepatocellular carcinoma, and death. The purpose of this summary is to review currently available clinical data to identify parameters that change in parallel with liver histology and are likely to reflect clinically meaningful reductions in the risk of developing cirrhosis and its complications. We review available data on exploratory histological, blood-based, and imaging pharmacodynamic biomarkers that may reflect meaningful treatment responses and provide recommendations regarding measurements to be considered in phase 2 and 3 trials as well as during postmarketing monitoring trials.

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Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

November 2019

Volume

70

Issue

5

Start / End Page

1841 / 1855

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Severity of Illness Index
  • Non-alcoholic Fatty Liver Disease
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Clinical Trials as Topic
  • 3204 Immunology
  • 3202 Clinical sciences
  • 1107 Immunology
 

Citation

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Cheung, A., Neuschwander-Tetri, B. A., Kleiner, D. E., Schabel, E., Rinella, M., Harrison, S., … Liver Forum Case Definitions Working Group, . (2019). Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum. Hepatology, 70(5), 1841–1855. https://doi.org/10.1002/hep.30672
Cheung, Amanda, Brent A. Neuschwander-Tetri, David E. Kleiner, Elmer Schabel, Mary Rinella, Stephen Harrison, Vlad Ratziu, et al. “Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum.Hepatology 70, no. 5 (November 2019): 1841–55. https://doi.org/10.1002/hep.30672.
Cheung A, Neuschwander-Tetri BA, Kleiner DE, Schabel E, Rinella M, Harrison S, et al. Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum. Hepatology. 2019 Nov;70(5):1841–55.
Cheung, Amanda, et al. “Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum.Hepatology, vol. 70, no. 5, Nov. 2019, pp. 1841–55. Pubmed, doi:10.1002/hep.30672.
Cheung A, Neuschwander-Tetri BA, Kleiner DE, Schabel E, Rinella M, Harrison S, Ratziu V, Sanyal AJ, Loomba R, Jeannin Megnien S, Torstenson R, Miller V, Liver Forum Case Definitions Working Group. Defining Improvement in Nonalcoholic Steatohepatitis for Treatment Trial Endpoints: Recommendations From the Liver Forum. Hepatology. 2019 Nov;70(5):1841–1855.
Journal cover image

Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

November 2019

Volume

70

Issue

5

Start / End Page

1841 / 1855

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Severity of Illness Index
  • Non-alcoholic Fatty Liver Disease
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Clinical Trials as Topic
  • 3204 Immunology
  • 3202 Clinical sciences
  • 1107 Immunology