Statins and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis

• Main Authors: Yu-Tse Tsan, 詹毓哲
• Other Authors: Pau-Chung Chen
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/26730035932364761489

博士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 101 === Background: Statins may have protective effects against cancer, but no studies have focused on their effects in patients with chronic hepatitis B and C virus infection. The prevalence rates of viral hepatitis are very high in Taiwan. The reimbursement database of National Health Insurance (NHI) in Taiwan provided an opportunity for surveillance. We conducted our study for four objectives; (1) to investigate whether statin use is associated with the reduction of hepatocellular carcinoma (HCC) incidence in hepatitis B virus (HBV) infected carriers; (2) to investigate whether statin use is associated with the reduction of HCC incidence in hepatitis C virus (HCV) infected patients; (3) to determine if there is a synergistic effect of statins, metformin, and thiazolidinediones (TZDs) on risk reduction of HCC in patients with HBV and/or diabetes; (4) to investigate the association between the use of nucleoside analogues (NAs), statins and the risk of HCC in HBV-infected patients. Methods: First part: we conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. A total of 33,413 HBV-infected patients were included as the study cohort. Each subject was individually tracked from 1997 to 2008 to identify incident cases of HCC since 1999. Subsequent use of statin, other lower-lipid agents, aspirin, and angiotensin-converting enzyme inhibitors were identified. Cox proportional hazard regressions were employed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the use of statins and the occurrence of HCC in the HBV-infected cohort. Second part: a population-based cohort study of 260,864 HCV-infected patients enrolled in the Taiwan National Health Insurance Research Database since January 1, 1999, and followed through December 31, 2010. Cox proportional hazards regression with time-dependent covariates for drug exposures was employed to evaluate the association between statin use and HCC risk. Third part: we conducted a population-based cohort study from the Taiwan National Health Insurance Research Database. A total of 33,413 HBV-infected patients were included as the study cohort. Each subject was individually tracked from 1997 to 2008 to identify incident cases of HCC since 1999. The diabetic prescriptions of medications that potentially could confound the association between statin use and cancer risk were also added, such as metformin and TZDs. Two Cox proportional hazard models were conducted with adjustment for different potential confounders to examine the association between HCC and the amounts of metformin and TZDs used. Forth part: A population-based matched cohort study of 91,265 HBV-infected patients enrolled in the Taiwan National Health Insurance Research Database since October, 2003 and December, 2010. 18,253 patients with NAs use were 1:4 matched as 73,012 patients without NAs use according to index date, age, sex, diabetes, liver cirrhosis, hypertension, hyperlipidemia, biliary tract stones, chronic renal injury, alcohol related diseases, and COPD. Cox proportional hazards regression model for drug exposures was employed to evaluate the association between NAs, statin use and HCC risk. Results: First part provides additional information on the use of statin, with the finding that statin use may reduce the risk for HCC in HBV-infected patients in a dose-dependent manner. Second part provides additional information on the use of statin, with the finding that statin use may reduce the risk for HCC in HCV-infected patients in a dose-dependent manner. Third part provides additional information on the use of statin, with the finding that there is a protective effect on HCC risk reduction of metformin and TZD use. Forth part provides clinical information on the use of NAs and statin, with the finding if there is a synergistic effect on HCC risk reduction in HBV-infected patients in Taiwan. Discussion: Statin use is dose-dependently associated with reduced risk for hepatocellular carcinoma in the presence of hepatitis B and hepatitis C viral infection. Statin use is an additional, convenient and acceptable strategy for preventing HCC in persons infected with hepatitis B and hepatitis C virus. The role of NAs and statins in cancer prevention continues to be an avenue for further investigation. A large-scale study is needed to clarify the association between HCC and the use of NAs, statin, metformin, and TZDs. Future studies should take into account the impact of these classes of pharmacological agents on reducing HCC risk, and adjust for them as potential confounders, even in clinical setting.