Role of bile acids in the diagnosis and progression of liver cirrhosis: A prospective observational study.

ABSTRACT

The accumulation of toxic bile acids (BAs) is closely related to liver injury, inflammation and tumorigenesis. The aim of the present study was to determine the role of the serum BA spectrum in the diagnosis and progression of liver cirrhosis. This was a prospective observational study involving patients with chronic hepatitis (n=23), liver cirrhosis (n=101), and cirrhosis complicated with hepatocellular carcinoma (CC-HCC; n=56). The 6-month survival of cirrhotic patients was recorded after blood collection. Comparisons of serum total BAs and individual BAs between different groups were performed using the Mann-Whitney U or Kruskal-Wallis tests. Correlation analysis was conducted by Spearman's correlation. Diagnosis and prediction analyses were performed using receiver operating characteristic curves. Survival was analyzed using the Kaplan-Meier method and multivariable Cox regression analysis. The concentrations of total BAs, glycocholic acid (GCA), glycochenodeoxycholic acid (GCDCA), taurocholic acid (TCA), taurochenoxycholic acid and tauroursodeoxycholic acid (TUDCA) were increased significantly in patients with early cirrhosis compared to patients with chronic hepatitis (P<0.05) and were associated with the diagnosis of cirrhosis (P=0.049, 0.004, 0.002, 0.003, 0.010 and 0.009, respectively). The levels of total BAs, primary conjugated BAs, and TUDCA increased as liver cirrhosis progressed (P<0.05). Serum total BAs, GCA, GCDCA, and TCA predicted the 6-month survival of patients with liver cirrhosis (P=0.0003, 0.005, 0.002, and 0.010 respectively). Based on multivariate Cox regression analysis, the level of total BAs was an independent predictor of mortality in cirrhotic patients (hazard ratios, 4.046; 95% CI, 1.620-10.108; P=0.003). In the early-stage cirrhosis group, the concentrations of total BAs and primary conjugated BAs were significantly elevated in patients with CC-HCC compared with patients with cirrhosis alone. In conclusion, total and individual BAs, especially primary conjugated BAs, are effective non-invasive markers in the diagnosis and prognosis of liver cirrhosis, and may be potential indicators in the occurrence of hepatocellular carcinoma in patients with early cirrhosis.