Understanding how fatty liver disease progresses from lipid accumulation to cirrhosis or liver cancer has long been hampered by a fragmented preclinical research landscape — dozens of animal, cell, and organoid models each capturing different facets of a highly heterogeneous condition. A formal consensus framework from Europe's leading liver society now attempts to rationalize this complexity, with significant implications for how future therapies are validated before reaching patients.
The European Association for the Study of the Liver (EASL) has issued a position paper cataloguing and evaluating the full spectrum of experimental models used to study steatotic liver disease (SLD) — an umbrella term covering metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), alcohol-associated liver disease (ALD), the intermediate MetALD category, and rarer drug-induced or monogenic causes. The paper systematically addresses in vivo (rodent and larger animal), in vitro (cell lines, primary hepatocytes), and ex vivo (precision-cut liver slices, organoids) platforms, assessing each for its fidelity to human disease across dimensions including steatosis, steatohepatitis, fibrosis, multi-organ crosstalk, and treatment response. MASLD and its inflammatory subtype MASH receive particular attention given their status as the leading cause of chronic liver disease globally.
This position paper arrives at a pivotal moment. The FDA approval of resmetirom for MASH in 2024 marked the field's first pharmacological milestone, yet clinical trial attrition remains high — partly because preclinical models often fail to predict human therapeutic outcomes. The EASL consensus is an attempt to establish shared standards, reducing the reproducibility crisis that has plagued hepatology research for years. Its principal limitation is inherent: no single preclinical model fully recapitulates the metabolic, immunological, and fibrotic complexity of human SLD, and translational gaps will persist regardless of standardization. Nonetheless, for researchers selecting model systems, and for regulators evaluating preclinical packages, this document represents an authoritative reference — incremental in ambition but potentially paradigm-clarifying in practice.