Association of Ursodeoxycholic Acid Use with Colorectal Cancer Risk---A Nationwide Cohort Study

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Ursodeoxycholic acid (UDCA) is a synthetic bile acid extensively used in the treatment of primary sclerosing cholangitis (PSC), primary biliary cirrhosis, and other chronic cholestatic liver diseases. A chemopreventive effect of UDCA on colorectal cancer (CRC) development has been reported in basic research and animal studies but is controversial in observational epidemiological studies and clinical trials with patients with PSC and ulcerative colitis (UC) (one form of inflammatory bowel disease, IBD). Furthermore, varied medication adherence measures used in literature are seldom used in Taiwan studies. In Taiwan, the high incidence of CRC, common use of UDCA for patients with chronic cholestatic liver diseases, and the availability of National Health Insurance Research Databases (NHIRDs) provide a unique opportunity to investigate the association between UDCA use and CRC development. We will use the NHIRDs to explore the following: (1) Among those who were prescribed UDCA, which diseases they had. (2) Compute 11 adherence measures for UDCA, and find out the comparability among them. (3) Explore the association between UDCA and CRC risk, especially focus on the adherence issue of UDCA. (4) Explore the association between UDCA and CRC risk for those who had IBD and compare the hazard ratio between those with Crohn’s disease (CD) and UC. We will conduct a population-based dynamic cohort study, including individuals with and without prescription of UDCA. UDCA users were defined as adults (age ? 20 years) who had received a prescription for UDCA (? 28 cumulative defined daily doses) from 2000 to 2012. Date of enrollment will be defined as the date on which UDCA was initially prescribed. We will exclude patients with a CRC diagnosis before enrollment. For each UDCA user, we will randomly select two UDCA nonusers as control patients. Nonusers will be matched for age, sex, enrollment date, and comorbidities related to chronic liver diseases (such as viral hepatitis A, viral hepatitis B, viral hepatitis C, cholelithiasis, alcoholic liver disease) and IBD. All UDCA users and nonusers will be observed until a diagnosis of CRC, death, or December 31, 2014, whichever occurred first. Survival analysis (log-rank test in univariate analysis and a time-dependent Cox proportional hazards model in multivariate analysis) will be used to examine the effect of UDCA on CRC prevention. Subgroup analysis will be performed for patients with IBD to compare the hazard ratio between those with CD and UC; and patients with hepatocellular carcinoma or intrahepatic cholangiocellular carcinoma excluded to sort out the competing risk problem.

Project IDs

Project ID:PC10408-1261
External Project ID:MOST104-2314-B182-009
Effective start/end date01/08/1531/07/16


  • ursodeoxycholic acid
  • colorectal cancer
  • adherence measures
  • chronic liver diseases


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