Cited by 74Liver Disease Diagnosis and TreatmentLiver Diseases and ImmunityLiver physiology and pathology

A critical review of endpoints for non-cirrhotic NASH therapeutic trials

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Ratziu, Vlad·2018·Journal of Hepatology

Abstract

Non-alcoholic steatohepatitis is a disease without a single, specific, diagnostic marker, hence multiple indicators are required to measure therapeutic efficacy. Moreover, drug candidates for non-alcoholic steatohepatitis target many distinct mechanisms that are believed to promote hepatic injury. Therefore, a wide range of endpoints must be reached, sequentially, as required by the drug development process. Some of these endpoints validate the mechanism of action, others are used to anticipate histological efficacy. Histological endpoints are still considered the best predictors of clinical outcome, but they can only be reliably tested in larger, late phase trials. Herein, we will review the rationale and clinical data supporting the use of specific endpoints at different stages of therapeutic trials. We will also discuss the validity and limitations of current phase IIb histological endpoints, particularly a one stage reduction in fibrosis, for their ability to predict progression to cirrhosis, which is the ultimate outcome measure in therapeutic trials.

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Research works printed but not linked: 2

  1. Loomba R, Kayali Z, Noureddin M, Ruane P, Lawitz E, Gitlin N, et al. Acetyl-CoA carboxylase (ACC) inhibitor GS-0976 leads to significant improvements in MRI-PDFF in a phase 2, randomized, placebo- controlled trial of patients with NASH. Hepatology 2017;66:1260A.
  2. Kleiner DE, Brunt EM, Belt P, Wilson LA, Guy CD, Yeh MM, et al. Diagnostic pattern and disease activity are related to disease progres- sion and regression in nonalcoholic fatty liver disease. Hepatology 2016;64:S247.

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Authors
Ratziu, V.
Affiliations
Inserm (FR)
Corresponding author
Ratziu, Vlad
Venue
Journal of Hepatology
Publisher
Elsevier BV
Published
2018-02
Volume
68
Issue
2
Pages
353-361
ISSN
0168-8278 (ISSN-L)
OpenAlex
W2774655822
Cited by
74
References
93
Citations by year
2026: 4 · 2025: 3 · 2024: 8 · 2023: 7 · 2022: 13 · 2021: 13 · 2020: 10 · 2019: 10 · 2018: 5 · 2017: 1
FWCI
0.94
Type
journal article
Language
en
Open access
Locations
  • Journal of Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
nonalcoholic steatohepatitis, clinical trial endpoints, fibrosis reduction, drug development
MeSH terms
Clinical Trials as Topic, Humans, Liver Cirrhosis, Prognosis, Disease Progression, Disease Management, Endpoint Determination, Non-alcoholic Fatty Liver Disease

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