biostudies-literatureUnknown16Murphy WA<h4>Introduction</h4>Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect ∼30% of adults globally. The progressive form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is a leading cause of chronic liver disease. MASH is marked by hepatocellular fat accumulation (steatosis), ballooning, and inflammation. Although many <i>in vitro</i> and <i>in vivo</i> models replicate MASH pathophysiology, no <i>in vitro</i> hepatocyte MASH model has been evaluated for its ability to reflect clinically observed changes in drug metabolizing enzymes (DMEs) and transporters. In this study, we addressed this gap by developing a model using sandwich-cultured human hepatocytes (SCHH) that mimics both MASH pathophysiology and alterations in DME and transporteFrontiers in pharmacology1664808https://www.ebi.ac.uk/biostudies/studies/S-EPMC12832903biostudies-literatureDevelopment of an <i>in vitro</i> metabolic dysfunction-associated steatohepatitis model to investigate altered drug metabolizing enzymes, transport proteins, and hepatobiliary disposition.PMC12832903Loop MSFallon JKMurphy WAKyburz SKralj TBrouwer KLRHo HTiley JBfalseDevelopment of an <i>in vitro</i> metabolic dysfunction-associated steatohepatitis model to investigate altered drug metabolizing enzymes, transport proteins, and hepatobiliary disposition.<h4>Introduction</h4>Metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated to affect ∼30% of adults globally. The progressive form of MASLD, metabolic dysfunction-associated steatohepatitis (MASH), is a leading cause of chronic liver disease. MASH is marked by hepatocellular fat accumulation (steatosis), ballooning, and inflammation. Although many <i>in vitro</i> and <i>in vivo</i> models replicate MASH pathophysiology, no <i>in vitro</i> hepatocyte MASH model has been evaluated for its ability to reflect clinically observed changes in drug metabolizing enzymes (DMEs) and transporters. In this study, we addressed this gap by developing a model using sandwich-cultured human hepatocytes (SCHH) that mimics both MASH pathophysiology and alterations in DME and transporte2025-01-01T00:00:00Z20252026-06-15T06:24:02.784Z2026-06-15T03:08:36.797ZS-EPMC128329034160195910.3389/fphar.2025.1664808