Use of bile acids as potential markers of liver dysfunction in humans: A systematic review

Medicine (Baltimore). 2021 Oct 15;100(41):e27464. doi: 10.1097/MD.0000000000027464.


Objective: This study aimed to determine the effectiveness of using total, individual serum, or urinary bile acids (BA) as potential markers of liver dysfunction.

Methods: We searched the PubMed and Web of Science databases using the following keywords- "serum bile acids," "liver dysfunction," "liver injury," "liver disease," "traditional liver function tests," "Chronic liver disease," "acute liver injury". The search was complemented by manual screening of the list of references for relevant articles. We selected only English-language manuscripts for adult patients based on predetermined inclusion and exclusion criteria. Animal studies and studies on neonates and children were not included.

Outcome measures: Changes in BA concentrations or ratios at or prior to changes in liver function tests.

Results: A total of 547 studies were identified, of which 28 were included after reading the entire manuscript. These studies included 1630 patients and 836 controls published between 1990 and 2017. The methods used in BA assays varied significantly, and the studies did not agree. on specific individual BA or BA ratios as biomarkers of specific liver injury or dysfunction. Except for the prognostic value of BA in intrahepatic cholestasis of pregnancy (ICP), studies have failed to provide evidence for BA as a liver biomarker.

Conclusions: Despite the research conducted on BA for over 27 years, there are inconsistencies in the reported results and a lack of solid evidence to support the use of individual BA or BA ratios as biomarkers of liver injury. Adequately conducted studies needed to resolve this limitation in the literature.

Publication types

  • Systematic Review

MeSH terms

  • Adult
  • Bile Acids and Salts / blood*
  • Bile Acids and Salts / urine*
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cholestasis, Intrahepatic / metabolism
  • Data Management
  • Female
  • Humans
  • Liver / injuries*
  • Liver / metabolism
  • Liver / physiopathology
  • Liver Diseases / diagnosis
  • Liver Diseases / metabolism*
  • Liver Function Tests / methods
  • Liver Function Tests / statistics & numerical data
  • Male
  • Pregnancy
  • Pregnancy Complications / metabolism
  • Sensitivity and Specificity


  • Bile Acids and Salts
  • Biomarkers

Supplementary concepts

  • Intrahepatic Cholestasis of Pregnancy