Liver biopsy for assessment of suspected drug‐induced liver injury in metabolic dysfunction‐associated steatohepatitis clinical trials: Expert consensus from the Liver Forum
Melissa Palmer, David E. Kleiner, Zachary Goodman, Elizabeth M. Brunt, Mark Avigan, Arie Regev, Paul H. Hayashi, James H. Lewis, Ruby Mehta, Stephen A. Harrison, Massimo Siciliano, Charles A. McWherter, Raj Vuppalanchi, Cynthia Behling, Veronica Miller, Naga Chalasani, Arun J. Sanyal
Abstract
BACKGROUND: Causality assessment of suspected drug-induced liver injury (DILI) during metabolic dysfunction-associated steatohepatitis (MASH) clinical trials can be challenging, and liver biopsies are not routinely performed as part of this evaluation. While the field is moving away from liver biopsy as a diagnostic and prognostic tool, information not identified by non-invasive testing may be provided on histology. AIM: To address the appropriate utilisation of liver biopsy as part of DILI causality assessment in this setting. METHODS: From 2020 to 2022, the Liver Forum convened a series of webinars on issues pertaining to liver biopsy during MASH trials. The Histology Working Group was formed to generate a series of consensus documents addressing these challenges. This manuscript focuses on liver biopsy as part of DILI causality assessment. RESULTS: Expert opinion, guidance and recommendations on the role of liver biopsy as part of causality assessment of suspected DILI occurring during clinical trials for a drug(s) being developed for MASH are provided. Lessons learned from prior MASH programs are reviewed and gaps identified. CONCLUSIONS: Although there are no pathognomonic features, histologic evaluation of suspected DILI during MASH clinical trials may alter patient management, define the pattern and severity of injury, detect findings that favour a diagnosis of DILI versus MASH progression, identify prognostic features, characterise the clinicopathological phenotype of DILI, and/or define lesions that influence decisions about trial discontinuation and further development of the drug.