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Front. Pharmacol. | doi: 10.3389/fphar.2018.00718

Association between cholangiocarcinoma and proton pump inhibitors use: a nested case-control study

 Yen-Chun Peng1, Cheng-Li Lin2, Wan-Yun Hsu1, Wai-Keung Chow1, Show-Wu Lee1, Hong-Zen Yeh1, Chia-Chang Chen1 and  Chia-Hung Kao2*
  • 1Taichung Veterans General Hospital, Taiwan
  • 2China Medical University, Taiwan

Background: The present study aimed to examine the odds of cholangiocarcinoma (CCA) in patients with proton pump inhibitors (PPIs) use.
Methods: A nested case-control study design was employed using data obtained from Taiwan’s National Health Insurance Research Database. In total, 2293 patients with confirmed diagnosis of CCA were identified and served as the CCA group. The CCA patients were propensity score-matched with 2293 subjects without CCA who served as the control group. The cumulative defined daily dose (DDD) of PPIs was calculated based on the total supply in days and quantity of individual PPIs. Univariable and multivariate logistic regression models were used to determine the odds of CCA, and calculated odds ratios (ORs) and 95% confidence intervals (CI) were used to assess PPIs use and odds of CCA.
Results: The overall adjusted OR of PPIs use-associated CCA was 2.58 (95% CI 2.27, 2.93). The adjusted OR of CCA by cumulative DDD dose of PPIs and CCA was analyzed and revealed those odds of CCA are associated with all types of PPIs.
Conclusions: There were odds of intrahepatic and extrahepatic CCA among PPIs users. All PPIs use was associated with odds of CCA. Analyses of larger numbers of cases are needed to confirm these findings.

Keywords: Cholangiocarcinoma, Proton Pump Inhibitors, case-control study, Defined daily dose, Odds ratios

Received: 19 Mar 2018; Accepted: 13 Jun 2018.

Edited by:

Dominique J. Dubois, Free University of Brussels, Belgium

Reviewed by:

Marc H. De Longueville, UCB Pharma (Belgium), Belgium
Gaurav Deshpande, HealthCore, Inc, United States  

Copyright: © 2018 Peng, Lin, Hsu, Chow, Lee, Yeh, Chen and Kao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Chia-Hung Kao, China Medical University, Taichung, Taiwan,