Conjugated bile acids in serum reflect disease severity and predict survival in chronic liver disease of humans and rats.

Abstract

Chronic liver diseases (CLD) are closely linked to an increased load of conjugated bile acids (BAs), which contribute to liver damage and inflammation, although many aspects remain unclear. This study investigated the relationships between serum conjugated BAs, BA-related gene expression in the liver and ileum, and survival outcomes in both human and rat models of CLD. Serum BA levels, including tauro- and glyco-conjugated BAs such as taurochenodeoxycholic acid (TCDCA), were measured in 73 CLD patients and in carbon tetrachloride (CCl)-induced CLD rat models using LC‒MS/MS. A higher conjugated-to-free BA ratio, elevated TCDCA levels, and a lower glycine-to-taurine ratio were significantly associated with impaired liver function, increased fibrosis markers, and worse survival rates in patients. Hepatic expression levels of BA-related genes were also associated with liver damage and survival rates in CLD rat models. The rat study suggested that increased serum conjugated BAs result from reduced intestinal excretion and enhanced bloodstream flow. These findings suggest that elevated serum conjugated BAs reflect disease severity and could serve as potential biomarkers for prognosis in CLD.