Abstract

BACKGROUND: Proton pump inhibitor (PPI) use has been reported to be associated with liver damage and might possibly be carcinogenic.

AIMS: We examined whether long-term PPI use increases the risk of hepatocellular carcinoma (HCC) in patients without viral hepatitis B or C.

METHODS: We conducted a nested case-control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29 473 HCC cases and 294 508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls).

RESULTS: The adjusted odds ratio (AOR) for HCC associated with PPI use was 2.86 (95% confidence interval [CI], 2.69-3.04). Considering the use of PPIs determined according to cumulative defined daily dose (cDDD) subgroups, a dose-response effect was observed in patients exposed to 29-180, 181-240, 241-300, and 300+ cDDDs of PPIs. The AORs were 2.74 (95% CI, 2.57-2.93), 2.98 (95% CI, 2.50-3.56), 3.23 (95% CI, 2.59-4.02), and 3.43 (95% CI, 2.94-4.00) in the 29-180, 181-240, 241-300, and 300+ cDDD groups, respectively, compared with the 0-28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC.

CONCLUSIONS: This observational study demonstrated that PPIs might increase the risk of HCC.

Original languageEnglish
JournalAlimentary Pharmacology and Therapeutics
DOIs
Publication statusE-pub ahead of print - Jun 13 2018

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Proton Pump Inhibitors
Hepatocellular Carcinoma
Confidence Intervals
Hepatitis C
Hepatitis B
Taiwan
Hepatitis
Observational Studies
Prescriptions
Case-Control Studies
Odds Ratio
Liver
Neoplasms

Cite this

@article{46c7dbc4c4574a8ca047315064ddca7b,
title = "Association between proton pump inhibitors and the risk of hepatocellular carcinoma",
abstract = "BACKGROUND: Proton pump inhibitor (PPI) use has been reported to be associated with liver damage and might possibly be carcinogenic.AIMS: We examined whether long-term PPI use increases the risk of hepatocellular carcinoma (HCC) in patients without viral hepatitis B or C.METHODS: We conducted a nested case-control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29 473 HCC cases and 294 508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls).RESULTS: The adjusted odds ratio (AOR) for HCC associated with PPI use was 2.86 (95{\%} confidence interval [CI], 2.69-3.04). Considering the use of PPIs determined according to cumulative defined daily dose (cDDD) subgroups, a dose-response effect was observed in patients exposed to 29-180, 181-240, 241-300, and 300+ cDDDs of PPIs. The AORs were 2.74 (95{\%} CI, 2.57-2.93), 2.98 (95{\%} CI, 2.50-3.56), 3.23 (95{\%} CI, 2.59-4.02), and 3.43 (95{\%} CI, 2.94-4.00) in the 29-180, 181-240, 241-300, and 300+ cDDD groups, respectively, compared with the 0-28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC.CONCLUSIONS: This observational study demonstrated that PPIs might increase the risk of HCC.",
author = "Shao, {Y-H J} and T-S Chan and K Tsai and S-Y Wu",
note = "{\circledC} 2018 John Wiley & Sons Ltd.",
year = "2018",
month = "6",
day = "13",
doi = "10.1111/apt.14835",
language = "English",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Association between proton pump inhibitors and the risk of hepatocellular carcinoma

AU - Shao, Y-H J

AU - Chan, T-S

AU - Tsai, K

AU - Wu, S-Y

N1 - © 2018 John Wiley & Sons Ltd.

PY - 2018/6/13

Y1 - 2018/6/13

N2 - BACKGROUND: Proton pump inhibitor (PPI) use has been reported to be associated with liver damage and might possibly be carcinogenic.AIMS: We examined whether long-term PPI use increases the risk of hepatocellular carcinoma (HCC) in patients without viral hepatitis B or C.METHODS: We conducted a nested case-control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29 473 HCC cases and 294 508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls).RESULTS: The adjusted odds ratio (AOR) for HCC associated with PPI use was 2.86 (95% confidence interval [CI], 2.69-3.04). Considering the use of PPIs determined according to cumulative defined daily dose (cDDD) subgroups, a dose-response effect was observed in patients exposed to 29-180, 181-240, 241-300, and 300+ cDDDs of PPIs. The AORs were 2.74 (95% CI, 2.57-2.93), 2.98 (95% CI, 2.50-3.56), 3.23 (95% CI, 2.59-4.02), and 3.43 (95% CI, 2.94-4.00) in the 29-180, 181-240, 241-300, and 300+ cDDD groups, respectively, compared with the 0-28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC.CONCLUSIONS: This observational study demonstrated that PPIs might increase the risk of HCC.

AB - BACKGROUND: Proton pump inhibitor (PPI) use has been reported to be associated with liver damage and might possibly be carcinogenic.AIMS: We examined whether long-term PPI use increases the risk of hepatocellular carcinoma (HCC) in patients without viral hepatitis B or C.METHODS: We conducted a nested case-control study in a cohort of patients without viral hepatitis in Taiwan from 2000 to 2013. In total, 29 473 HCC cases and 294 508 matched controls were included. Moreover, we identified prescriptions for PPI and durations between the PPI index date and cancer diagnosis date (or the corresponding date in controls).RESULTS: The adjusted odds ratio (AOR) for HCC associated with PPI use was 2.86 (95% confidence interval [CI], 2.69-3.04). Considering the use of PPIs determined according to cumulative defined daily dose (cDDD) subgroups, a dose-response effect was observed in patients exposed to 29-180, 181-240, 241-300, and 300+ cDDDs of PPIs. The AORs were 2.74 (95% CI, 2.57-2.93), 2.98 (95% CI, 2.50-3.56), 3.23 (95% CI, 2.59-4.02), and 3.43 (95% CI, 2.94-4.00) in the 29-180, 181-240, 241-300, and 300+ cDDD groups, respectively, compared with the 0-28 cDDD group. A sensitivity analysis revealed a consistent association between PPI use and the risk of HCC in subpopulations stratified by risk factors associated with HCC.CONCLUSIONS: This observational study demonstrated that PPIs might increase the risk of HCC.

U2 - 10.1111/apt.14835

DO - 10.1111/apt.14835

M3 - Article

C2 - 29897132

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

ER -