Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C

Wei-Yu Kao, Chien-Wei Su, Elise Chia-Hui Tan, Pei-Chang Lee, Ping-Hsien Chen, Jui-Hsiang Tang, Yi-Hsiang Huang, Teh-Ia Huo, Chun-Chao Chang, Ming-Chih Hou, Han-Chieh Lin, Jaw-Ching Wu

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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 pair 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 PPIs 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 HCC in the 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 dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed PPI use was not correlated to an increased HCC risk. Conclusions Based on a retrospective, nationwide population-based cohort study in 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. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalHepatology
DOIs
Publication statusE-pub ahead of print - Sep 2 2018

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Proton Pump Inhibitors
Chronic Hepatitis B
Chronic Hepatitis C
Hepatocellular Carcinoma
Hepatitis B virus
Hepacivirus
Virus Diseases
Taiwan
Propensity Score
National Health Programs
Proportional Hazards Models
Prescriptions
Comorbidity
Cohort Studies
Multivariate Analysis
Research Personnel
Databases
Confidence Intervals

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Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C. / Kao, Wei-Yu; Su, Chien-Wei; Tan, Elise Chia-Hui; Lee, Pei-Chang; Chen, Ping-Hsien; Tang, Jui-Hsiang; Huang, Yi-Hsiang; Huo, Teh-Ia; Chang, Chun-Chao; Hou, Ming-Chih; Lin, Han-Chieh; Wu, Jaw-Ching.

In: Hepatology, 02.09.2018.

Research output: Contribution to journalArticle

Kao, Wei-Yu ; Su, Chien-Wei ; Tan, Elise Chia-Hui ; Lee, Pei-Chang ; Chen, Ping-Hsien ; Tang, Jui-Hsiang ; Huang, Yi-Hsiang ; Huo, Teh-Ia ; Chang, Chun-Chao ; Hou, Ming-Chih ; Lin, Han-Chieh ; Wu, Jaw-Ching. / Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C. In: Hepatology. 2018.
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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 pair 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 PPIs 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 HCC in the 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 dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed PPI use was not correlated to an increased HCC risk. Conclusions Based on a retrospective, nationwide population-based cohort study in 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. This article is protected by copyright. All rights reserved.",
author = "Wei-Yu Kao and Chien-Wei Su and Tan, {Elise Chia-Hui} and Pei-Chang Lee and Ping-Hsien Chen and Jui-Hsiang Tang and Yi-Hsiang Huang and Teh-Ia Huo and Chun-Chao Chang and Ming-Chih Hou and Han-Chieh Lin and Jaw-Ching Wu",
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journal = "Hepatology",
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T1 - Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C

AU - Kao, Wei-Yu

AU - Su, Chien-Wei

AU - Tan, Elise Chia-Hui

AU - Lee, Pei-Chang

AU - Chen, Ping-Hsien

AU - Tang, Jui-Hsiang

AU - Huang, Yi-Hsiang

AU - Huo, Teh-Ia

AU - Chang, Chun-Chao

AU - Hou, Ming-Chih

AU - Lin, Han-Chieh

AU - Wu, Jaw-Ching

N1 - This article is protected by copyright. All rights reserved.

PY - 2018/9/2

Y1 - 2018/9/2

N2 - 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 pair 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 PPIs 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 HCC in the 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 dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed PPI use was not correlated to an increased HCC risk. Conclusions Based on a retrospective, nationwide population-based cohort study in 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. This article is protected by copyright. All rights reserved.

AB - 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 pair 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 PPIs 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 HCC in the 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 dose-dependent effect of PPI use and HCC risk. Subgroup analysis also confirmed PPI use was not correlated to an increased HCC risk. Conclusions Based on a retrospective, nationwide population-based cohort study in 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. This article is protected by copyright. All rights reserved.

U2 - 10.1002/hep.30247

DO - 10.1002/hep.30247

M3 - Article

JO - Hepatology

JF - Hepatology

SN - 0270-9139

ER -