Introduction and Context
Metabolic dysfunction–associated steatohepatitis (MASH), within the newly framed spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD), remains a leading indication for liver-related morbidity in adults with obesity and type 2 diabetes. Histologic assessment of liver biopsies — grading necroinflammatory activity and staging fibrosis — remains the gold standard for patient selection and primary endpoints in most therapeutic clinical trials. Yet variability in how pathologists define and score core histologic features (notably hepatocyte ballooning, lobular inflammation, and distribution of fibrosis) creates major problems: high inter- and intra-observer variability, inconsistent trial enrollment (screening failures), and variable placebo response rates that can obscure treatment effects.
To address these problems, the International MASLD Pathology Group (IMPG), a panel of 25 expert liver pathologists plus a statistician, developed consensus position statements to standardize histologic definitions, specimen handling, scoring use, and reader workflows specifically for MASH clinical trials. Their work, published in J Hepatol (Lackner et al., 2025), used a multi-stage Delphi process to arrive at a robust set of recommendations intended to improve reproducibility, facilitate multicenter trials, and support generation of high-quality annotated datasets for machine learning.
