Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: A nationwide high-risk cohort study

Cheng Maw Ho, Chih Hsin Lee, Ming Chia Lee, Jun Fu Zhang, Jann Yuan Wang, Rey Heng Hu, Po Huang Lee

研究成果: 雜誌貢獻文章

4 引文 (Scopus)

摘要

Background: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated. Methods: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders. Results: Among the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81-1.16) and 0.96 (0.80-1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46-14.1). Conclusion: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.
原文英語
文章編號401
期刊BMC Cancer
18
發行號1
DOIs
出版狀態已發佈 - 四月 10 2018

指紋

Angiotensin Receptor Antagonists
Chemoprevention
Angiotensin-Converting Enzyme Inhibitors
Hepatocellular Carcinoma
Hepacivirus
Cohort Studies
Hepatitis B virus
Hyperlipidemias
Diabetes Mellitus
Confidence Intervals
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Metformin
Virus Diseases
Taiwan
Liver Cirrhosis
Aspirin
Antiviral Agents
Comorbidity
Fibrosis
Databases

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

引用此文

Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma : A nationwide high-risk cohort study. / Ho, Cheng Maw; Lee, Chih Hsin; Lee, Ming Chia; Zhang, Jun Fu; Wang, Jann Yuan; Hu, Rey Heng; Lee, Po Huang.

於: BMC Cancer, 卷 18, 編號 1, 401, 10.04.2018.

研究成果: 雜誌貢獻文章

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title = "Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma: A nationwide high-risk cohort study",
abstract = "Background: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated. Methods: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders. Results: Among the 7724 patients with HBV and 7873 with HCV, 46.3{\%} and 42.5{\%}, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95{\%} confidence interval [CI]: 0.81-1.16) and 0.96 (0.80-1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95{\%} CI: 1.46-14.1). Conclusion: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.",
keywords = "Angiotensin II receptor blockers, Angiotensin-converting enzyme inhibitors, Chemoprevention, Comparative effectiveness, Hepatocellular carcinoma, High-risk cohort",
author = "Ho, {Cheng Maw} and Lee, {Chih Hsin} and Lee, {Ming Chia} and Zhang, {Jun Fu} and Wang, {Jann Yuan} and Hu, {Rey Heng} and Lee, {Po Huang}",
year = "2018",
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journal = "BMC Cancer",
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TY - JOUR

T1 - Comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in chemoprevention of hepatocellular carcinoma

T2 - A nationwide high-risk cohort study

AU - Ho, Cheng Maw

AU - Lee, Chih Hsin

AU - Lee, Ming Chia

AU - Zhang, Jun Fu

AU - Wang, Jann Yuan

AU - Hu, Rey Heng

AU - Lee, Po Huang

PY - 2018/4/10

Y1 - 2018/4/10

N2 - Background: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated. Methods: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders. Results: Among the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81-1.16) and 0.96 (0.80-1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46-14.1). Conclusion: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.

AB - Background: Research has revealed that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may prevent cancers such as hepatocellular carcinoma (HCC). The comparative chemopreventive effects of ACEIs and ARBs in high-risk populations with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection have yet to be investigated. Methods: From 2005 to 2014, high-risk HBV and HCV cohorts of hypertensive patients without HCC history were recruited from three linked national databases of Taiwan, and were classified into two groups based on the ACEI or ARB exposure within the initial six months after initiating antiviral agent. Intergroup differences in clinical characteristics and duration of drug exposure within study period were evaluated. HCC-free survival was compared using the log-rank test. Multivariate Cox regression including time-dependent variables for the use of ACEIs or ARBs and other medications was applied to adjust for confounders. Results: Among the 7724 patients with HBV and 7873 with HCV, 46.3% and 42.5%, respectively, had an initial exposure to ACEIs or ARBs. The median durations of exposure were 36.4 and 38.9 months for the HBV and HCV cohorts, respectively. The median durations of ACEI or ARB use during study period between initial exposure and nonexposure groups were 41.8 vs. 18.3 months and 46.4 vs. 22.7 months for the HBV and HCV cohorts, respectively. No significant difference was observed in HCC risk within 7 years between the initial exposure and non-exposure groups. After adjustment for comorbidities, namely liver cirrhosis, diabetes mellitus (DM), and hyperlipidemia, and medications, namely aspirin, metformin, and statins, the hazard ratios (HRs) for ACEI or ARB exposure for HCC risk were 0.97 (95% confidence interval [CI]: 0.81-1.16) and 0.96 (0.80-1.16) in the HBV and HCV cohorts, respectively. In the HCV cohort, the increased HCC risk was associated with ACEI or ARB use in patients without cirrhosis, DM, and hyperlipidemia (HR: 4.53, 95% CI: 1.46-14.1). Conclusion: Compared with other significant risk and protective factors for HCC, ACEI or ARB use in the HBV and HCV cohorts was not associated with adequate protective effectiveness under standard dosages and may not be completely safe.

KW - Angiotensin II receptor blockers

KW - Angiotensin-converting enzyme inhibitors

KW - Chemoprevention

KW - Comparative effectiveness

KW - Hepatocellular carcinoma

KW - High-risk cohort

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U2 - 10.1186/s12885-018-4292-y

DO - 10.1186/s12885-018-4292-y

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