4.1 Article

Human Hepatocellular response in Cholestatic Liver Diseases

Journal

ORGANOGENESIS
Volume 19, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/15476278.2023.2247576

Keywords

Cholestasis; hepatocellular response; human hepatocytes; primary biliary cholangitis; primary sclerosing cholangitis; >

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This study characterizes hepatocytes isolated from explanted livers of patients with PBC and PSC. The findings reveal changes in intracellular bile acid levels, oxidative stress, and expression of hepatocyte-specific genes in these diseases. These insights provide a basis for understanding the hepatocellular response to cholestasis in cholestatic liver diseases and support the use of hepatocytes as an experimental tool for studying these diseases.
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), the most common types of cholestatic liver disease (CLD), result in enterohepatic obstruction, bile acid accumulation, and hepatotoxicity. The mechanisms by which hepatocytes respond to and cope with CLD remain largely unexplored. This study includes the characterization of hepatocytes isolated from explanted livers of patients with PBC and PSC. We examined the expression of hepatocyte-specific genes, intracellular bile acid (BA) levels, and oxidative stress in primary-human-hepatocytes (PHHs) isolated from explanted livers of patients with PBC and PSC and compared them with control normal human hepatocytes. Our findings provide valuable initial insights into the hepatocellular response to cholestasis in CLD and help support the use of PHHs as an experimental tool for these diseases.

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