@article{f6a745c828514dcaa320630fc8c45109,
title = "Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B or C",
abstract = "Researchers have hypothesized that the long-term use of proton pump inhibitors (PPIs) can increase the risk of developing cancer. However, the association between PPI use and hepatocellular carcinoma (HCC) risk is unclear. Using data from the Taiwan National Health Insurance Research Database for the period between 2003 and 2013, we identified 35,356 patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections. One-to-one propensity score matching by gender, age, cohort entry year, comorbidity, and medication resulted in the inclusion of 7,492 pairs of patients (PPI users and non-PPI users) for analyses. We performed multivariate and stratified analysis using the Kaplan-Meier method and Cox proportional hazards models in order to estimate the association between PPI use and the risk of developing HCC. In the HBV cohort, 237 patients developed HCC during a median follow-up of 53 months. However, PPI use was not associated with an increased risk of developing HCC (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 0.90-1.73; P = 0.18). In the HCV cohort, 211 patients developed HCC; but again, PPI use was not associated with an increase in the risk of developing HCC (aHR, 1.19; 95% CI, 0.88-1.61; P = 0.25). We observed no relationship between a dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed that PPI use was not correlated to an increased HCC risk. Conclusion: Based on a retrospective population-based cohort study throughout Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections.",
author = "Kao, {Wei Yu} and Su, {Chien Wei} and {Chia-Hui Tan}, Elise and Lee, {Pei Chang} and Chen, {Ping Hsien} and Tang, {Jui Hsiang} and Huang, {Yi Hsiang} and Huo, {Teh Ia} and Chang, {Chun Chao} and Hou, {Ming Chih} and Lin, {Han Chieh} and Wu, {Jaw Ching}",
note = "Funding Information: Received May 8, 2018; accepted August 21, 2018. Additional Supporting Information may be found at onlinelibrary.wiley.com/doi/10.1002/hep.30247/suppinfo. Part of this study was presented as a poster presentation at the fifty-third annual meeting of the European Association for the Study of the Liver, Paris, France, April 11-15, 2018. Supported by grants from the Ministry of Science and Technology of Taiwan (MOST 106-2314-B-038-030) and Taipei Veterans General Hospital (V106C-122, Center of Excellence for Cancer Research MOHW107-TDU-B-211-114019). Editorial support was funded by the National Research Institute of Chinese Medicine. {\textcopyright} 2018 by the American Association for the Study of Liver Diseases. View this article online at wileyonlinelibrary.com. DOI 10.1002/hep.30247 Potential conflict of interest: Dr. Kao is on the speakers{\textquoteright} bureau for Abbvie, Bristol-Myers Squibb, Gilead, and Roche. Dr. Su advises and is on the speakers{\textquoteright} bureau for Gilead. Dr. Su is on the speakers{\textquoteright} bureau for Bristol-Myers Squibb, Abbvie, Bayer, and Roche. Funding Information: The data used in this study were obtained from the LHID, which is maintained by the Taiwan National Health Research Institute. In brief, the single-payer mandatory National Health Insurance (NHI) program was implemented in 1995 and currently covers >99% of the 23 million residents in Taiwan. The LHID is a longitudinal database that contains all individual medical claims from 1 million enrollees randomly sampled from the NHI registry since 1995. The NHI enrollees included in the LHID do not differ significantly from the overall population of NHI enrollees in terms of age, gender, or overall health care costs. Claims data of patients with HBV or HCV include all ambulatory visits, hospital admissions, treatments, and medications prescribed under the NHI system. The antiviral therapy for HBV and HCV has been reimbursed by the NHI since 2003. The accuracy of the diagnoses of major diseases in the National Health Insurance Research Database (NHIRD), such as diabetes mellitus and stroke, has been validated. Furthermore, substantial studies have been conducted based on diagnostic coding from the LHID, including studies pertaining to HCC. The current research was approved by the institutional review board of Taipei Veterans General Hospital (2017-10-002CC). Consent waivers were obtained, and all identifying information of patients in the LHID is anonymized. The data used in this study were obtained from the LHID, which is maintained by the Taiwan National Health Research Institute. Publisher Copyright: {\textcopyright} 2018 by the American Association for the Study of Liver Diseases",
year = "2019",
month = mar,
doi = "10.1002/hep.30247",
language = "English",
volume = "69",
pages = "1151--1164",
journal = "Hepatology",
issn = "0270-9139",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}
