Hepatotoxicity of Bile Acids with Special Reference to Cheno-Treatment

Abstract

Hepatotoxic effects of several bile acids of minor polarity especially lithocholic acid (LC) have been demonstrated in experimental animals, but species differences in metabolism of and the response to administered bile acids militate against extrapolations to man, in whom direct evidence for hepatotoxicity of bile acids is lacking. Treatment with chenodeoxycholic acid (CDC) for cholesterol gallstones or hyperlipidemia leads to increased exposure of the liver to CDC and its metabolites LC and ursodeoxycholic acid (UDC). Severe dose-related toxic effects on the liver have been observed in animals fed CDC, but sulfation of LC and rapid excretion seem to be protective in man. Reduced risk may be obtained by administration of UDC which also dissolve gallstones but at a much smaller dose.

Incomplete or abnormal hydroxylations during bile acid formation due to hepatic injury lead to very complex metabolic bile acid profiles. The physiological significance of abnormal bile acid profiles is not clear, but hepatotoxic effects of particular bile acids in selfperpetuating processes have been suggested.