A critical review of endpoints for non-cirrhotic NASH therapeutic trials
Open accessAbstract
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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Among the histologic features of MASH, fibrosis is the only one whose severity correlates with clinical outcomes.
“Among the histologic features of MASH, fibrosis is the only one whose severity correlates with clinical outcomes (286-288).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [286]
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Self-citation
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Research works printed but not linked: 2
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The Treatment Progression of Obeticholic Acid in Non-Alcoholic Fatty Liver Disease
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- Authors
- Ratziu, V.
- Affiliations
- Inserm (FR)
- Corresponding author
- Ratziu, Vlad
- ORCID
- 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
- bronze
- doi.org
- 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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