Differential diagnosis between benign and malignant biliary stenosis can be difficult in clinical practice. Histology of biopsy specimens is often indeterminate. Laboratory markers (serum bilirubin > 75 μmol/L, carbohydrate antigen 19-9 > 400 U/mL) and the length of stenosis (>15 mm) can be helpful but are not specific enough. The aim of this study was to investigate bile acids in liver bile of patients with benign and malignant biliary stenosis and controls without stenosis. A total of 73 patients entered the study: 7 subjects with benign biliary stenosis (6 men, 1 woman; 68 ± 13 years old), 21 with malignant biliary stenosis (15 men, 6 women; 72 ± 14 years old), and 45 patients without biliary stenosis (22 men, 23 women; 70 ± 13 years old); out of those, 25 subjects have and 20 do not have choledocholithiasis. Twenty-three different bile acids were investigated by high-performance liquid chromatography/mass spectrometry. Serum total bilirubin was significantly higher in patients with malignant biliary stenosis compared with nonstenotic controls (p = 0.005). Significant relationship (r > 0.7) was found between several pairs of bile acids. Significantly lower bile acid concentrations in malignant biliary stenosis compared to controls without stenosis were found for GLCA (p = 0.032), GUDCA (p = 0.032), GCDCA (p = 0.006), GDCA (p = 0.031), GHCA (p = 0.005), TUDCA (p = 0.044), and TDCA (p = 0.036). Significant difference in cholic acid was found between benign and malignant stenosis (p = 0.022). Analysis of bile acids might be helpful in the differential diagnosis of malignant and benign biliary stenosis. More patients need to be enrolled in further studies so that the real diagnostic yield of bile acids can be determined.

2nd Department of Internal Medicine Gastroenterology Charles University Faculty of Medicine in Hradec Kralove and University Hospital Sokolska 581 500 05 Hradec Kralove Czech Republic

Department of Medical Biochemistry Charles University Faculty of Medicine in Hradec Kralove Zborovska 2089 500 03 Hradec Kralove Czech Republic

The Royal Marsden Hospital NHS Foundation Trust Fulham Road Chelsea SW3 6JJ London UK

Zobrazit více v PubMed

Bain V. G., Abraham N., Jhangri G. S., et al. Prospective study of biliary strictures to determine the predictors of malignancy. Canadian Journal of Gastroenterology. 2000;14(5):397–402. doi: 10.1155/2000/467567. PubMed DOI

Buis C. I., Geuken E., Visser D. S., et al. Altered bile composition after liver transplantation is associated with the development of nonanastomotic biliary strictures. Journal of Hepatology. 2009;50(1):69–79. doi: 10.1016/j.jhep.2008.07.032. PubMed DOI

Park J. Y., Park B. K., Ko J. S., Bang S., Song S. Y., Chung J. B. Bile acid analysis in biliary tract cancer. Yonsei Medical Journal. 2006;47(6):817–825. doi: 10.3349/ymj.2006.47.6.817. PubMed DOI PMC

Lankisch T. O., Metzger J., Negm A. A., et al. Bile proteomic profiles differentiate cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis. Hepatology. 2011;53(3):875–884. doi: 10.1002/hep.24103. PubMed DOI

Jusakul A., Khuntikeo N., Haigh W. G., et al. Identification of biliary bile acids in patients with benign biliary diseases, hepatocellular carcinoma and cholangiocarcinoma. Asian Pacific Journal of Cancer Prevention. 2012;13:77–82. PubMed

Metzger J., Negm A. A., Plentz R. R., et al. Urine proteomic analysis differentiates cholangiocarcinoma from primary sclerosing cholangitis and other benign biliary disorders. Gut. 2013;62(1):122–130. doi: 10.1136/gutjnl-2012-302047. PubMed DOI

Arbelaiz A., Azkargorta M., Krawczyk M., et al. Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma. Hepatology. 2017;66(4):1125–1143. doi: 10.1002/hep.29291. PubMed DOI

Loosen S. H., Roderburg C., Kauertz K. L., et al. Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma. Journal of Hepatology. 2017;67(4):749–757. doi: 10.1016/j.jhep.2017.06.020. PubMed DOI

Mischak H. Method and marker for the diagnosis of a bile duct stricture and of a cholangiocellular carcinoma in bile. US Patent US20140027283A1, 2014.

Voigtländer T., Metzger J., Schönemeier B., et al. A combined bile and urine proteomic test for cholangiocarcinoma diagnosis in patients with biliary strictures of unknown origin. United European Gastroenterology Journal. 2017;5(5):668–676. doi: 10.1177/2050640616687836. PubMed DOI PMC

Galle P. R., Theilmann L., Raedsch R., Otto G., Stiehl A. Ursodeoxycholate reduces hepatotoxicity of bile salts in primary human hepatocytes. Hepatology. 1990;12(3):486–491. doi: 10.1002/hep.1840120307. PubMed DOI

Schmucker D. L., Ohta M., Kanai S., Sato Y., Kitani K. Hepatic injury induced by bile salts: correlation between biochemical and morphological events. Hepatology. 1990;12(5):1216–1221. doi: 10.1002/hep.1840120523. PubMed DOI

Arrese M., Trauner M. Molecular aspects of bile formation and cholestasis. Trends in Molecular Medicine. 2003;9(12):558–564. doi: 10.1016/j.molmed.2003.10.002. PubMed DOI

Alvaro D., Gigliozzi A., Attili A. F. Regulation and deregulation of cholangiocyte proliferation. Journal of Hepatology. 2000;33(2):333–340. doi: 10.1016/S0168-8278(00)80377-3. PubMed DOI

Alpini G., Glaser S., Alvaro D., et al. Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3-kinase–dependent pathway in rats. Gastroenterology. 2002;123(4):1226–1237. doi: 10.1053/gast.2002.36055. PubMed DOI

Xia X., Francis H., Glaser S., Alpini G., LeSage G. Bile acid interactions with cholangiocytes. World Journal of Gastroenterology. 2006;12(22):3553–3563. doi: 10.3748/wjg.v12.i22.3553. PubMed DOI PMC

Lozano E., Sanchez-Vicente L., Monte M. J., et al. Cocarcinogenic effects of intrahepatic bile acid accumulation in cholangiocarcinoma development. Molecular Cancer Research. 2014;12(1):91–100. doi: 10.1158/1541-7786.MCR-13-0503. PubMed DOI

Zuo P., Dobbins R. L., O'Connor-Semmes R. L., Young M. A. A systems model for ursodeoxycholic acid metabolism in healthy and patients with primary biliary cirrhosis. CPT: Pharmacometrics & Systems Pharmacology. 2016;5(8):418–426. doi: 10.1002/psp4.12100. PubMed DOI PMC