DOI QR코드

DOI QR Code

Total Serum Bile Acid as a Potential Marker for the Diagnosis of Cholangiocarcinoma without Jaundice

  • Sombattheera, Sutthikan (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Proungvitaya, Tanakorn (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Limpaiboon, Temduang (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University) ;
  • Wongkham, Sopit (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Wongkham, Chaisiri (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Luvira, Vor (Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Proungvitaya, Siriporn (Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University)
  • 발행 : 2015.03.09

초록

Diagnosis of cholangiocarcinoma (CCA) is difficult when patients do not show jaundice. The aim of this study was to examine the feasibility of using the total serum bile acid (TSBA) level as an aid for the diagnosis of CCA in patients without jaundice. For this purpose, TSBA of the following groups were measured using a Beckman Synchron CX4 clinical chemistry analyzer: 60 cases of CCA with total serum bilirubin ${\leq}2mg/dL$ (low total bilirubin group, LTB); 32 cases of CCA with total serum bilirubin >2 mg/dL (high total bilirubin group, HTB); and 115 healthy controls. Liver function parameters such as serum cholesterol, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were also examined. The results showed that the TSBA of both LTB and HTB groups of the CCA patients were significantly higher than that of the healthy controls. Also, significant correlation was observed between TSBA and total bilirubin levels in the HTB group of CCA patients. However, no such correlation was seen in the LTB group. The cut-off value of TSBA was determined for the LTB group of CCA patients using the receiver operating characteristic curve analysis, and it was $6.05{\mu}mol/L$ with the sensitivity and specificity of 46.7% and 84.4%, respectively. In addition, the ALP level was correlated well with the TSBA level and ALP in HTB group was significantly higher than that of LTB group. Moreover, the combination of high TSBA and high ALP levels gave higher specificity up to 97.4%. TSBA might be useful for the diagnosis of CCA patients without jaundice.

키워드

참고문헌

  1. Al Mamari S, Djordjevic J, Halliday JS, et al (2013). Improvement of serum alkaline phosphatase to <1.5 upper limit of normal predicts better outcome and reduced risk of cholangiocarcinoma in primary sclerosing cholangitis. J Hepatol, 58, 329-34. https://doi.org/10.1016/j.jhep.2012.10.013
  2. Bhudhisawasdi V, Khuntikeo N, Chur-in S, et al (2012). Cholangiocarcinoma: experience of Srinagarind hospital. Srinagarind Med J, 27, 331-9.
  3. Blechacz BR, Gores GJ (2008). Cholangiocarcinoma. Clin Liver Dis, 12, 131-50. https://doi.org/10.1016/j.cld.2007.11.003
  4. Braconi C, Patel T (2010). Cholangiocarcinoma: new insights into disease pathogenesis and biology. Infect Dis Clin North Am, 24, 871-84. https://doi.org/10.1016/j.idc.2010.07.006
  5. Changbumrung S, Tungtrongchitr R, Migasena P, et al (1990). Serum unconjugated primary and secondary bile acids in patients with cholangiocarcinoma and hepatocellular carcinoma. J Med Assoc Thai, 73, 81-90.
  6. Fausa O, Gjone E (1976). Serum bile acid concentrations in patients with liver disease. Scand J Gastroenterol, 11, 537-43.
  7. Heaton KW (1979). Bile salt tests in clinical practice. Br Med J, 1, 644-6. https://doi.org/10.1136/bmj.1.6164.644
  8. Jusakul A, Khuntikeo N, Haigh WG, et al (2012). Identification of biliary bile acids in patients with benign biliary diseases, hepatocellular carcinoma and cholangiocarcinoma. Asian Pac J Cancer Prev, 13, 77-82.
  9. Motawa E. El- Houseine, Mahmoud A. Amer, Abdel Hakim Saad El-Din, et al (2000). Evaluation of serum total bile acids in the diagnosis of hepatocellular carcinoma. J Egypt Natl Cancer Inst, 12, 307-13.
  10. Shaffer EA, Gordon ER (1978). Serum bile acids as related to bile acid secretion in liver disease. Am J Dig Dis, 23, 392-7. https://doi.org/10.1007/BF01072920
  11. Sripa B, Bethony JM, Sithithaworn P, et al (2011). Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Trop, 120, 158-68. https://doi.org/10.1016/j.actatropica.2010.07.006
  12. Sripa B, Kaewkes S, Sithithaworn P, et al (2007). Liver fluke induces cholangiocarcinoma. PLoS Med, 4, 201. https://doi.org/10.1371/journal.pmed.0040201
  13. Stanich PP, Bjornsson E, Gossard AA, et al (2011). Alkaline phosphatase normalization is associated with better prognosis in primary sclerosing cholangitis. Dig Liver Dis, 43, 309-13. https://doi.org/10.1016/j.dld.2010.12.008
  14. Sugiyama M, Atomi Y, Kuroda A, et al (1997). Bile duct carcinoma without jaundice: clues to early diagnosis. Hepatogastroenterology, 44, 1477-83.
  15. Tabibian N (1988). Serum bile acid levels in liver disease: is there a clinical application? South Med J, 81, 281-2. https://doi.org/10.1097/00007611-198802000-00036
  16. Webster CR, Usechak P, Anwer MS (2002). cAMP inhibits bile acidinduced apoptosis by blocking caspase activation and cytochrome c release. Am J Physiol Gastrointest Liver Physiol, 283, 727-38. https://doi.org/10.1152/ajpgi.00410.2001
  17. Wiangnon S, Suwanrungruang K, Kamsa-Ard S (2012). Cholangiocarcinoma in Khon Kaen Province. Srinagarind Med J, 27, 326-30.
  18. Wongkham S, Silsirivanit A (2012). State of serum markers for detection of cholangiocarcinoma. Asian Pac J Cancer Prev, 13 Suppl, 17-27.
  19. Zografos GN, Farfaras A, Zagouri F, et al (2011). Cholangiocarcinoma: principles and current trends. Hepatobiliary Pancreat Dis Int, 10, 10-20. https://doi.org/10.1016/S1499-3872(11)60001-5

피인용 문헌

  1. Development of an enzyme-linked immunosorbent assay for chenodeoxycholic acid using an anti-chenodeoxycholic acid monoclonal antibody vol.7, pp.11, 2015, https://doi.org/10.1039/C5AY00733J
  2. Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis pp.02709139, 2019, https://doi.org/10.1002/hep.30319