Predictive value of serum bile acids as metabolite biomarkers for liver cirrhosis: a systematic review and meta-analysis.

Introduction: A large number of studies have explored the potential biomarkers for detecting liver cirrhosis in an early stage, yet consistent conclusions are still warranted.

Objectives: To conduct a review and a meta-analysis of the existing studies that test the serum level of bile acids in cirrhosis as the potential biomarkers to predict cirrhosis.

Methods: Six databases had been searched from inception date to April 12, 2021. Screening and selection of the records were based on the inclusion criteria. The risk of bias was assessed with the Newcastle-Ottawa quality assessment scale (NOS). Mean difference (MD) and confidence intervals 95% (95% CI) were calculated by using the random effect model for the concentrations of bile acids in the meta-analysis, and I statistic was used to measure studies heterogeneity. This study was registered on PROSPERO.

Results: A total of 1583 records were identified and 31 studies with 2679 participants (1263 in the cirrhosis group, 1416 in the healthy control group) were included. The quality of included studies was generally high, with 25 studies (80.6%) rated over 7 stars. A total of 45 bile acids or their ratios in included studies were extracted. 36 increased in the cirrhosis group compared with those of the healthy controls by a qualitative summary, 5 decreased and 4 presented with mixing results. The result of meta-analysis among 12 studies showed that 13 bile acids increased, among which four primary conjugated bile acids showed the most significant elevation in the cirrhosis group: GCDCA (MD = 11.38 μmol/L, 95% CI 8.21-14.55, P < 0.0001), GCA (MD = 5.72 μmol/L, 95% CI 3.47-7.97, P < 0.0001), TCDCA (MD = 3.57 μmol/L, 95% CI 2.64-4.49, P < 0.0001) and TCA (MD = 2.14 μmol/L, 95% CI 1.56-2.72, P < 0.0001). No significant differences were found between the two groups in terms of DCA (MD = - 0.1 μmol/L, 95% CI - 0.18 to - 0.01, P < 0.0001) and LCA (MD = - 0.01 μmol/L, 95% CI - 0.01 to - 0.02, P < 0.0001), UDCA (MD = - 0.14 μmol/L, 95% CI - 0.04 to - 0.32, P < 0.0001), and TLCA (MD = 0 μmol/L, 95% CI 0-0.01, P < 0.0001). Subgroup analysis in patients with hepatitis B cirrhosis showed similar results.

Conclusion: Altered serum bile acids profile seems to be associated with cirrhosis. Some specific bile acids (GCA, GCDCA, TCA, and TCDCA) may increase with the development of cirrhosis, which possibly underlay their potential role as predictive biomarkers for cirrhosis. Yet this predictive value still needs further investigation and validation in larger prospective cohort studies.