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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1534628
This article is part of the Research Topic New Targets and Strategies for the Prevention and Treatment of Organ Fibrosis, Volume III View all 8 articles

Adverse events of hepatic anti-fibrotic agents in phase 3 and above clinical trials: a descriptive analysis of the WHO-VigiAccess database

Provisionally accepted
Yuwei Liu Yuwei Liu Zhao Xu Zhao Xu Xinrui Wang Xinrui Wang *Qiang Zhou Qiang Zhou *
  • Department of Hepatology, The First Hospital of Jilin University, Changchun, China

The final, formatted version of the article will be published soon.

    Introduction: Liver fibrosis is a pathological condition in response to chronic liver injuries.Currently, there is no Food and Drug Administration (FDA) approved pharmacotherapy for liver fibrosis. Advances in understanding hepatic fibrogenesis have led to the development of antifibrotic agents, and some of them have shown promise in phase 3 and above clinical trials.However, adverse drug reactions (ADRs) associated with emerging anti-fibrotic agents may hinder their efficacy and clinical applicability. This study assessed ADRs associated with anti-fibrotic agents as reported in the World Health Organization (WHO) VigiAccess database and compared the adverse reaction characteristics of these agents for optimizing therapeutic strategies.Methods: A detailed search was conducted on ClinicalTrial.gov to identify phase 3 or 4 clinical trials involving hepatic anti-fibrotic agents. The ADR reports were retrieved from the WHO-VigiAccess database, with data categorized by demographic characteristics, geographic distribution, and System Organ Classes (SOCs). The most frequently reported ADRs were identified through descriptive analysis. Disproportionality analysis, measured by reporting odd ratio (ROR) and proportional report ratio (PRR), was performed to evaluate ADRs related to gastrointestinal disorders.Results: Five hepatic anti-fibrotic agents (empagliflozin, liraglutide, candesartan, obeticholic acid, and resmetirom) were identified. A total of 130,567 ADR reports were analyzed, with empagliflozin, liraglutide, and candesartan showing significantly higher ADRs. The most frequently reported SOCs included gastrointestinal disorders (29.44%), general disorders (24.12%), and nervous system disorders (14.42%). Liraglutide demonstrated a higher risk of

    Keywords: liver fibrosis, Adverse drug reactions (ADRs), Anti-fibrotic agents, WHO-Vigiaccess, descriptive analysis, Disproportionality analysis

    Received: 26 Nov 2024; Accepted: 06 Jan 2025.

    Copyright: © 2025 Liu, Xu, Wang and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xinrui Wang, Department of Hepatology, The First Hospital of Jilin University, Changchun, China
    Qiang Zhou, Department of Hepatology, The First Hospital of Jilin University, Changchun, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.