Abstract

Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV. Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N=71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors. In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.48-0.57) for all cancers, 0.28 (95% CI, 0.23-0.35) for liver cancer, and 0.63 (95% CI, 0.57-0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.75-0.90) for all cancers, 0.97 (95% CI, 0.84-1.14) for liver cancer, and 0.75 (95% CI, 0.67-0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use. This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose- response effect in reducing the incidence of cancer with a dose- response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.

Original languageEnglish
Article numbere462
JournalMedicine (United States)
Volume94
Issue number6
DOIs
Publication statusPublished - Feb 2 2015

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Metformin
Hepatitis B virus
Cohort Studies
Population
Neoplasms
Liver Neoplasms
Confidence Intervals
Incidence
Hepatocellular Carcinoma
Virus Diseases
Inflammation
Chemoprevention
Health Insurance

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Cancer risk in HBV patients with statin and metformin use a population-based cohort study. / Chen, Chang-I; Kuan, Ching Feng; Fang, Yu Ann; Liu, Shing Hwa; Liu, Ju-Chi; Wu, Li Li; Chang, Chun Jen; Yang, Hsuan Chia; Hwang, Jau-Lang; Miser, James; Wu, Szu-Yuan.

In: Medicine (United States), Vol. 94, No. 6, e462, 02.02.2015.

Research output: Contribution to journalArticle

Chen, Chang-I ; Kuan, Ching Feng ; Fang, Yu Ann ; Liu, Shing Hwa ; Liu, Ju-Chi ; Wu, Li Li ; Chang, Chun Jen ; Yang, Hsuan Chia ; Hwang, Jau-Lang ; Miser, James ; Wu, Szu-Yuan. / Cancer risk in HBV patients with statin and metformin use a population-based cohort study. In: Medicine (United States). 2015 ; Vol. 94, No. 6.
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abstract = "Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV. Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N=71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors. In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95{\%} confidence interval [CI], 0.48-0.57) for all cancers, 0.28 (95{\%} CI, 0.23-0.35) for liver cancer, and 0.63 (95{\%} CI, 0.57-0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95{\%} CI, 0.75-0.90) for all cancers, 0.97 (95{\%} CI, 0.84-1.14) for liver cancer, and 0.75 (95{\%} CI, 0.67-0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use. This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose- response effect in reducing the incidence of cancer with a dose- response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.",
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T1 - Cancer risk in HBV patients with statin and metformin use a population-based cohort study

AU - Chen, Chang-I

AU - Kuan, Ching Feng

AU - Fang, Yu Ann

AU - Liu, Shing Hwa

AU - Liu, Ju-Chi

AU - Wu, Li Li

AU - Chang, Chun Jen

AU - Yang, Hsuan Chia

AU - Hwang, Jau-Lang

AU - Miser, James

AU - Wu, Szu-Yuan

PY - 2015/2/2

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N2 - Chronic infection with hepatitis B virus (HBV) often causes chronic inflammation of the liver with an increased incidence of hepatocellular carcinoma (HCC). HBV-infected individuals may also have an increased incidence of nonliver cancers. Taking statin or metformin may decrease inflammation and infiltration, which may, as a result, reduce the risk of liver cancer or other major cancers in patients with HBV infection. The purpose of this study was to evaluate the hypothesis that statin and metformin could reduce the incidence of liver cancer (HCC) or nonliver cancers in patients with HBV. Using the Taiwan Longitudinal Health Insurance Database 2000 to 2008, this cohort study comprised patients with a recorded diagnosis of HBV (N=71,847) between January 1, 2000 and December 31, 2008. Each patient was followed-up until the end of 2008. The occurrence of HCC or a nonliver cancer was evaluated in patients who either were or were not taking statin or metformin. Cox proportional hazard regressions were used to evaluate the cancer incidence after adjusting for known confounding factors. In total, 71,824 HBV-infected patients comprised the study cohort. Our study showed that either metformin or statin use was associated with a reduction in the incidence of cancer. This was most prominent in patients taking both statin and metformin. The adjusted hazard ratios (HRs) for patients using only statin were 0.52 (95% confidence interval [CI], 0.48-0.57) for all cancers, 0.28 (95% CI, 0.23-0.35) for liver cancer, and 0.63 (95% CI, 0.57-0.70) for nonliver cancers. Patients taking only metformin had risk-adjusted HRs of 0.82 (95% CI, 0.75-0.90) for all cancers, 0.97 (95% CI, 0.84-1.14) for liver cancer, and 0.75 (95% CI, 0.67-0.84) for nonliver cancers. A dose-dependent effect of statin use for chemoprevention was observed for all cancers, including both liver cancer and nonliver cancers. A dose-dependent effect of metformin was also seen in liver cancer and nonliver cancers without stratification into different cumulative daily doses of statin use. This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose- response effect in reducing the incidence of cancer with a dose- response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.

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