A systematic review

Abstract 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 27years, 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.

[1]  S. Elserougy,et al.  Serum bile acid as a screening tool in workers occupationally exposed to mixtures of organic solvents , 2014, Toxicology and industrial health.

[2]  A. Hofmann,et al.  Key discoveries in bile acid chemistry and biology and their clinical applications: history of the last eight decades , 2014, Journal of Lipid Research.

[3]  B. Seckin,et al.  Role of postprandial bile acids in prediction of perinatal outcome in intrahepatic cholestasis of pregnancy , 2014, The journal of obstetrics and gynaecology research.

[4]  Joel L Cohen,et al.  An Interrater and Intrarater Reliability Study of 3 Photographic Scales for the Classification of Perioral Aesthetic Features , 2014, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[5]  L. Bull,et al.  Serum bile acids in intrahepatic cholestasis of pregnancy: Not just a diagnostic test , 2014, Hepatology.

[6]  Min Ding,et al.  Primary bile acids as potential biomarkers for the clinical grading of intrahepatic cholestasis of pregnancy , 2013, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[7]  Z. Halpern,et al.  Serum bile acid levels as a predictor for the severity of liver fibrosis in patients with chronic hepatitis C , 2013, Journal of viral hepatitis.

[8]  S. Lucangioli,et al.  In Search of an Accurate Evaluation of Intrahepatic Cholestasis of Pregnancy , 2012, Scientifica.

[9]  Patrick Caron,et al.  Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study. , 2012, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[10]  R. Straka,et al.  Profiling Circulating and Urinary Bile Acids in Patients with Biliary Obstruction before and after Biliary Stenting , 2011, PloS one.

[11]  S. Kalhan,et al.  Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis , 2011, European journal of gastroenterology & hepatology.

[12]  W. Vogel,et al.  Pruritus of unknown origin and elevated total serum bile acid levels in patients without clinically apparent liver disease , 2011, Journal of gastroenterology and hepatology.

[13]  P. Seed,et al.  Longitudinal Profiles of 15 Serum Bile Acids in Patients With Intrahepatic Cholestasis of Pregnancy , 2010, The American Journal of Gastroenterology.

[14]  J. G. Donnelly,et al.  Bile acid ratio in diagnosis of intrahepatic cholestasis of pregnancy. , 2009, American journal of perinatology.

[15]  T. Nagayasu,et al.  Clinical significance of measuring urinary sulfated bile acids in adult patients with hepatobiliary diseases. , 2009, Hepato-gastroenterology.

[16]  T. Kamano,et al.  Studies of serum and feces bile acids determination by gas chromatography-mass spectrometry. , 2006, Rinsho byori. The Japanese journal of clinical pathology.

[17]  M. E. Pereira,et al.  Increased serum bile acids as a possible biomarker of hepatotoxicity in Brazilian workers exposed to solvents in car repainting shops , 2005, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[18]  Rui-feng Yang,et al.  An enzymatic cycling method for the determination of serum total bile acids with recombinant 3alpha-hydroxysteroid dehydrogenase. , 2004, Biochemical and biophysical research communications.

[19]  A. Zanella,et al.  Updated Definitions of Healthy Ranges for Serum Alanine Aminotransferase Levels , 2002, Annals of Internal Medicine.

[20]  G. Testa,et al.  Serum bile acids in liver transplantation – early indicator for acute rejection and monitor for antirejection therapy , 2001, Transplant international : official journal of the European Society for Organ Transplantation.

[21]  C. Williamson,et al.  Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis , 2001, BJOG : an international journal of obstetrics and gynaecology.

[22]  G. Mazzella,et al.  Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: Effects on primary bile acids in babies and mothers , 2001, Hepatology.

[23]  W. Stremmel,et al.  Kinetics of primary bile acids in patients after orthotopic liver transplantation , 1996, European journal of clinical investigation.

[24]  K. Byth,et al.  Sequential changes in serum levels of individual bile acids in patients with chronic cholestatic liver disease , 1996, Journal of gastroenterology and hepatology.

[25]  J. Schölmerich,et al.  Early detection of graft dysfunction after orthotopic liver transplantation in man by serum and biliary bile acid analysis. , 1995, Hepato-gastroenterology.

[26]  J. Collazos Glycocholic acid in chronic active hepatitis and mild liver diseases , 1993, The clinical investigator.

[27]  S. Azer,et al.  Daily determination of individual serum bile acids allows early detection of hepatic allograft dysfunction , 1993, Hepatology.

[28]  N. LaRusso,et al.  Determinants of fasting and postprandial serum bile acid levels in healthy man , 1978, The American Journal of Digestive Diseases.

[29]  L. Demers,et al.  Radioimmunoassay of bile acids in serum. , 1976, Clinical chemistry.

[30]  T. J. Lalisang,et al.  Serum bile acid: an alternative liver function marker in the obstructive jaundice patient. , 2012, Acta medica Indonesiana.

[31]  M. Neghab,et al.  Raised concentration of serum bile acids following occupational exposure to halogenated solvents, 1,1,2-trichloro-1,2,2-trifluoroethane and trichloroethylene , 1997, International archives of occupational and environmental health.

[32]  S. Azer,et al.  Standard Liver Function Tests and Their Limitations: Selectivity and sensitivity of individual serum bile acid levels in hepatic dysfunction , 1997 .

[33]  B. Balkau,et al.  Serum bile acids and cholestasis in alcoholic hepatitis. Relationship with usual liver tests and histological features. , 1994, Journal of hepatology.

[34]  J. de Miguel,et al.  Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests. , 1993, Gastroenterologie clinique et biologique.

[35]  P. Melone,et al.  Mechanism of intestinal 7 alpha-dehydroxylation of cholic acid: evidence that allo-deoxycholic acid is an inducible side-product. , 1991, Journal of lipid research.

[36]  R. Tungtrongchitr,et al.  Serum unconjugated primary and secondary bile acids in patients with cholangiocarcinoma and hepatocellular carcinoma. , 1990, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.