Development of an in vitro metabolic dysfunction-associated steatohepatitis model to investigate altered drug metabolizing enzymes, transport proteins, and hepatobiliary disposition.

ABSTRACT:

Introduction

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 in vitro and in vivo models replicate MASH pathophysiology, no in vitro 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 transporte

SUBMITTER: Murphy WA 

PROVIDER: S-EPMC12832903 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature