Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis.

ABSTRACT: Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increa

SUBMITTER: Woolbright BL 

PROVIDER: S-EPMC4361327 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature