Serum levels of total bile acids are associated with an increased risk of HCC in patients with cirrhosis.

Background: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

Methods: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid when added to a previously validated clinical model.

Results: We analyzed data from 940 patients with cirrhosis, of whom 68 patients progressed to HCC during 3406 person-years of follow-up. Higher baseline serum TBA level was significantly associated with an increased risk of developing HCC with an adjusted HR of 3.69 (95% CI = 1.85-7.37) for the highest versus lowest tertile. TBA levels significantly increased predictive ability for progression to HCC at 2 years of follow-up; the c statistic increased from 0.74 to 0.80 (p < 0.001). There was evidence for a significant interaction between TBA level and hepatitis C (p = 0.04).

Conclusions: In a large prospective cohort study, the prediagnostic serum level of TBAs was associated with a significant increase in the risk of developing HCC among patients with multi-etiology cirrhosis. The TBA-associated risk was additive to that of established demographic and clinical predictors.