Cancer Risk in HBV Patients With Statin and Metformin Use

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.

Statin use is associated with a reduced risk of hepatocellular carcinoma recurrence after initial liver resection

“…The morbidity and major complication rates were similar between the groups. The postoperative hospital stay was significantly shorter in the statin than non-statin group [13 (10-16) days vs. 15 (12)(13)(14)(15)(16)(17)(18)(19) days, P = 0.022].…”

“…The protective effects of statins against the development of HCC were recently indicated in patients with hepatitis B (11)(12)(13) and hepatitis C (14,15), although conflicting results have also been reported (16). Use of nucleoside analogues, statins, and nonsteroidal anti-inflammatory drugs (NSAIDs)/ aspirin were reportedly associated with a reduced risk of HCC recurrence in patients with hepatitis B, who underwent liver resection (17).…”

The Role of Nuclear Receptors in the Pathophysiology, Natural Course, and Drug Treatment of NAFLD in Humans

“…In short, on the basis of current evidence metformin [262,263], statins [264,265], or their combination [266] may potentially be useful in this setting. However, most data derive from observational studies and RCTs are warranted before chemoprevention of HCC can be licensed for clinical practice.…”

Recurrent aphthous stomatitis may be a precursor or risk factor for specific cancers: A case‐control frequency‐matched study

“…The NHIRD is maintained by the NHI program, which is a compulsory program established in 1995 that insures 99% of all residents of Taiwan (approximately 23 million). Hundreds of articles based on NHIRD data have been published in peer‐reviewed international journals14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26 and the detailed data provided in these articles have supported the work of physicians and policymakers 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26. Individual information was anonymized before the NHIRD was released for research purposes.…”