Yu-Tse Tsan

Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis B Virus Infection

PURPOSEnStatins have potential protective effects against cancers, but no studies have focused on patients with chronic hepatitis B virus (HBV) infection. The purpose of this study was to investigate the association between the use of statins in HBV-infected patients and the risk of hepatocellular carcinoma (HCC).nnnPATIENTS AND METHODSnWe 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 patient was individually tracked from 1997 to 2008 to identify incident cases of HCC since 1999. Subsequent use of statin, other lipid-lowering agents, aspirin, and angiotensin-converting enzyme inhibitors was identified. Cox proportional hazards regression was used to calculate the hazard ratios (HRs) and 95% CIs for the association between the use of statins and the occurrence of HCC in the HBV-infected cohort.nnnRESULTSnThere were 1,021 HCCs in the HBV cohort during the follow-up period of 328,946 person-years; the overall incidence rate was 310.4 HCCs per 100,000 person-years. There was a dose-response relationship between statin use and the risk of HCC in the HBV cohort. The adjusted HRs were 0.66 (95% CI, 0.44 to 0.99), 0.41 (95% CI, 0.27 to 0.61), and 0.34 (95% CI, 0.18 to 0.67) for statin use of 28 to 90, 91 to 365, and more than 365 cumulative defined daily doses (cDDDs), respectively, relative to no statin use (< 28 cDDDs).nnnCONCLUSIONnStatin use may reduce the risk for HCC in HBV-infected patients in a dose-dependent manner. Further mechanistic research is needed.

Statins and the Risk of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection

PURPOSEnStatins may have protective effects against cancer, but no studies have focused on their effects in patients with chronic hepatitis C virus (HCV) infection. The purpose of this study was to investigate the association between use of statins and risk of hepatocellular carcinoma (HCC) in HCV-infected patients.nnnPATIENTS AND METHODSnOurs was 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 observed 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.nnnRESULTSnThere were 27,883 cases of HCC in the HCV cohort during a follow-up period of 2,792,016.6 person-years. Among the 35,023 patients using statins (defined as ≥ 28 cumulative defined daily doses [cDDDs]), 1,378 had HCC. Among the 225,841 patients not using statins (< 28 cDDDs), 26,505 were diagnosed with HCC. A dose-response relationship between statin use and HCC risk was observed. The adjusted hazard ratios were 0.66 (95% CI, 0.59 to 0.74), 0.47 (95% CI, 0.40 to 0.56), and 0.33 (95% CI, 0.25 to 0.42) for patients with 28 to 89, 90 to 180, and > 180 cDDDs per year, respectively, relative to nonusers. The reduction in risk also demonstrated a progressive duration-response relationship in patients with ≥ 28 cDDDs per year when compared with nonusers.nnnCONCLUSIONnAmong patients with HCV infection, statin use was associated with reduced risk of HCC. Further research is needed to elucidate the mechanism responsible for this effect.

Hepatitis C viral infection and the risk of dementia.

Hepatitis C virus (HCV) infection may cause cognitive impairment, but no studies have focused specifically on cognitive impairment stemming from HCV. The purpose of this study was to investigate the potential increased risk for dementia in HCV‐infected patients.

Use of Thiazolidinediones and the Risk of Colorectal Cancer in Patients With Diabetes: A nationwide, population-based, case-control study

OBJECTIVE Preclinical data suggest that peroxisome proliferator–activated receptor γ (PPARγ) agonists have antineoplastic effects in colorectal cancer. We aimed to assess the association between the use of synthetic PPARγ agonists, represented by thiazolidinediones (TZDs), and the risk of developing colorectal cancer. RESEARCH DESIGN AND METHODS We conducted a nationwide, population-based, case-control study using the Taiwan National Health Insurance Research Database. Case subjects were defined as patients who were diagnosed with diabetes at least 365 days prior to a new diagnosis of colorectal cancer between 2000 and 2008. We randomly selected diabetic control subjects for each case subject, which were matched by sex, age, and the duration of diabetes. Among the 24,496 eligible case subjects and control subjects, we used conditional logistic regression to assess the risk of colorectal cancer in association with the use of TZDs. An additional analysis was conducted to assess the effects of concomitant use of TZDs and low-dose aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) on the risk of colorectal cancer. RESULTS A decreased risk of colorectal cancer was observed in patients who had used TZDs compared with those who had never used TZDs (adjusted odds ratio 0.86 [95% CI 0.79–0.94]). Furthermore, the benefit of a decreased colorectal cancer risk was also found with concomitant use of TZDs and low-dose aspirin or NSAIDs. CONCLUSIONS The use of TZDs may be associated with a decreased risk of colorectal cancer in patients with diabetes. Further studies are warranted to confirm our findings.

Statins and the risk of pancreatic cancer in Type 2 diabetic patients—A population-based cohort study

The aim of this study was to determine whether statin use exerts a protective effect against pancreatic cancer in Type 2 diabetic patients. A retrospective population‐based cohort study was designed to analyze the National Health Insurance Research database (NHIRD) from 1997–2010 in Taiwan. A total of 1,140,617 patients with a first‐time diagnosis of Type 2 diabetes were enrolled. The event was defined as newly diagnosed pancreatic cancer. A Cox proportional hazards regression model with time‐dependent covariates was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of pancreatic cancer associated with statin use in the diabetic cohort. A total of 2,341 patients with newly diagnosed pancreatic cancer were identified in the diabetic cohort during the follow‐up period of 6,968,217.1 person‐years. In this cohort, 450,282 patients were defined as statin users (statin use ≥28 cumulative defined daily dose [cDDD] in 1 year) and 0.14% had pancreatic cancer; 690,335 patients were statin nonusers (statin use <28 cDDD in 1 year) and 0.25% had pancreatic cancer. Statin use significantly decreased the risk of pancreatic cancer (adjusted HRs: 0.78 in 28–83 cDDD per year; 0.48 in 84–180 cDDD per year; and 0.33 in >180 cDDD per year) after adjusting for multiple confounders. There was a significant dose‐effect of statin use for the risk of pancreatic cancer (p for trend: <0.001). Statin use may be associated with a reduced risk of pancreatic cancer in Type 2 diabetic patients. More research is needed to clarify this association.

Use of an α-Glucosidase Inhibitor and the Risk of Colorectal Cancer in Patients With Diabetes: A Nationwide, Population-Based Cohort Study

OBJECTIVE Acarbose, an α-glucosidase inhibitor, has been shown to have antineoplastic effects on colorectal cancer in biomarker studies. We assessed the association between acarbose use in patients with diabetes and incident colorectal cancer. RESEARCH DESIGN AND METHODS We conducted a nationwide, population-based study using a large cohort with diabetes in the Taiwan National Health Insurance Research Database. Patients with newly diagnosed diabetes (n = 1,343,484) were enrolled between 1998 and 2010. One control subject not using acarbose was randomly selected for each subject using acarbose after matching for age, sex, diabetes onset, and comorbidities. Cox proportional hazards regression with a competing risks analysis was used to calculate the hazard ratios (HRs) and 95% CIs for the association between acarbose use and incident colorectal cancer for each eligible case-control pair (n = 199,296). RESULTS There were 1,332 incident cases of colorectal cancer in the cohort with diabetes during the follow-up period of 1,487,136 person-years. The overall incidence rate was 89.6 cases per 100,000 person-years. Patients treated with acarbose had a 27% reduction in the risk of colorectal cancer compared with control subjects. The adjusted HRs were 0.73 (95% CI 0.63–0.83), 0.69 (0.59–0.82), and 0.46 (0.37–0.58) for patients using >0 to <90, 90 to 364, and ≥365 cumulative defined daily doses of acarbose, respectively, compared with subjects who did not use acarbose (P for trend < 0.001). CONCLUSIONS Acarbose use reduced the risk of incident colorectal cancer in patients with diabetes in a dose-dependent manner.

Angiotensin-converting enzyme inhibitors enhance the effect of cyclooxygenase inhibitors on breast cancer: a nationwide case-control study

Objectives: Angiotensin-converting enzyme (ACE) inhibitors are first-line antihypertensive and potential cancer preventive agents. Interest in breast cancer prevention is growing, and more clinical evidence is needed regarding the effects of preventive therapy, alone or in combination. Methods: This was a nationwide case–control analysis from the Taiwan National health Insurance Research Database. We analyzed 16u200a847 female breast cancer patients (diagnosed between 1 January 2002 and 31 December 2008) and 50u200a541 matched individuals. Longitudinal exposure to ACE inhibitors and cyclooxygenase inhibitors was compared. Results: The risk of developing breast cancer among patients taking both aspirin and an ACE inhibitor decreased as the ACE inhibitor dose increased. Among patients receiving between 28 and 364 cumulative defined daily doses (cDDDs) of aspirin, the adjusted odds ratios (ORs) were 0.97 (0.90–1.06), 0.91 (0.82–1.03), and 0.79 (0.68–0.92) for women taking ACE inhibitors for 0–27, 28–364, and more than 365 cDDD, respectively. Among women receiving more than 365 cDDD of aspirin, the adjusted ORs were 0.91 (0.80–1.03), 0.81 (0.70–0.94), and 0.81 (0.71–0.92) as the ACE inhibitor dose increased, respectively. Women taking nonaspirin NSAIDs along with an ACE inhibitor had the same finding. Among women taking 28–364 cDDD of NSAIDs, the adjusted ORs were 0.85 (0.81–0.89), 0.87 (0.81–0.94), and 0.80 (0.73–0.88); for women receiving more than 365 cDDD of NSAIDs, the adjusted ORs were 0.68 (0.62–0.74), 0.61 (0.53–0.70), and 0.60 (0.52–0.70) as the ACE inhibitor dose increased, respectively. Conclusion: The findings of this nationwide analysis support the hypothesis that ACE inhibitors enhance the antitumor effect of cyclooxygenase inhibitors on breast cancer.

Authors' reply to: Statins and the risk of pancreatic cancer in type 2 diabetic patients: Immortal time bias in survival analysis?

1 Institute of Occupational Medicine and Industry Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 3 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 4 Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 5 Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Reply to: Statins and the risk of pancreatic cancer in type 2 diabetic patients: Immortal time bias in survival analysis? ‐Author reply

1 Institute of Occupational Medicine and Industry Hygiene, National Taiwan University College of Public Health, Taipei, Taiwan 2 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 3 Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan 4 Department of Emergency Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 5 Environmental and Occupational Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

Herbal medicine containing aristolochic acid and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection: Aristolochic Acid and Risk of HCC

It was suspected that aristolochic acid‐induced mutations may be associated with hepatitis B virus (HBV), playing an important role in liver carcinogenesis. The purpose of this study was to investigate the association between the use of Chinese herbs containing aristolochic acid and the risk of hepatocellular carcinoma (HCC) among HBV‐infected patients. We conducted a retrospective, population‐based, cohort study on patients older than 18 years who had a diagnosis of HBV infection between January 1, 1997 and December 31, 2010 and had visited traditional Chinese medicine clinics before one year before the diagnosis of HCC or the censor dates. A total of 802,642 HBV‐infected patients were identified by using the National Health Insurance Research Database in Taiwan. The use of Chinese herbal products containing aristolochic acid was identified between 1997 and 2003. Each patient was individually tracked from 1997 to 2013 to identify incident cases of HCC since 1999. There were 33,982 HCCs during the follow‐up period of 11,643,790 person‐years and the overall incidence rate was 291.8 HCCs per 100,000 person‐years. The adjusted hazard ratios (HRs) were 1.13 (95% confidence interval [CI], 1.11–1.16), 1.21 (95% CI, 1.13–1.29), 1.37 (95% CI, 1.24–1.50) and 1.61 (95% CI, 1.40–1.84) for estimated aristolochic acid of 1–250, 251–500, 501–1,000 and more than 1,000 mg, respectively, relative to no aristolochic acid exposure. Our study found a significant dose–response relationship between the consumption of aristolochic acid and HCC in patients with HBV infection, suggesting that aristolochic acid which may be associated with HBV plays an important role in the pathogenesis of HCC.