Bile acids as drivers and biomarkers of hepatocellular carcinoma

The prevalence of hepatocellular carcinoma (HCC) is rapidly increasing, driven not least in part by the escalating prevalence of non-alcoholic fatty liver disease. Bile acid (BA) profiles are altered in patients with HCC and there is a developing body of evidence from in vitro human cellular models as well as rodent data suggesting that BA are able to modulate fundamental processes that impact on cellular phenotype predisposing to the development of HCC including senescence, proliferation and epithelial-mesenchymal transition. Changes in BA profiles associated with HCC have the potential to be exploited clinically. Whilst excellent diagnostic and imaging tools are available, their use to screen populations with advanced liver disease at risk of HCC is limited by high cost and low availability. The mainstay for HCC screening among subjects with cirrhosis remains frequent interval ultrasound scanning. Importantly, currently available serum biomarkers add little to diagnostic accuracy. Here, we review the current literature on the use of BA measurements as predictors of HCC incidence in addition to their use as a potential screening method for the early detection of HCC. Whilst these approaches do show early promise, there are limitations including the relatively small cohort sizes, the lack of a standardized approach to BA measurement, and the use of inappropriate control comparator samples.