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Am J Cancer Res. 2017 Jul 1;7(7):1606-1616. eCollection 2017.

The role of thiazolidinediones in hepatocellular carcinoma risk reduction: a population-based cohort study in Taiwan.

Author information

1
Division of Gastroenterology, Department of Internal Medicine, Taoyuan Armed Forces General HospitalTaoyuan County, Taiwan.
2
Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical CenterTaipei, Taiwan.
3
School of Public Health, National Defense Medical CenterTaipei, Taiwan.
4
Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical CenterTaipei, Taiwan.
5
Division of Gastroenterology, Department of Internal Medicine, Hualien Armed Forces General HospitalHualien County, Taiwan.
6
Department of Medical Research, Tri-Service General Hospital, National Defense Medical CenterTaipei, Taiwan.

Abstract

OBJECTIVES:

The aim of this study was to investigate the effect of thiazolidinediones (TZDs) on the risk of hepatocellular carcinoma (HCC) development among diabetes mellitus (DM) patients.

METHODS:

We conducted a population-based case-control study in Taiwan based on data from the Taiwan National Health Insurance Research Database. A total of 76,349 newly diagnosed DM patients were identified from claims between 2000 and 2010. Among diabetics, 3,026 and 12,104 patients respectively, received or did not receive TZDs. Comparison frequency was matched with age, sex, and index date, excluding those with cancer at baseline. The incidence of HCC at the end of 2010 and the risks associated with the presence of hepatitis B and C infections were analyzed. The effect of TZDs use on the reduction of HCC risk was also assessed.

RESULTS:

The incidence of HCC was lower in the TZD cohort compared with the non-TZD cohort (418.3 vs. 484.6 per 100,000 person-years), with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval = 0.38-0.77) using multivariable Cox proportional hazard regression. In the stratified analysis, HCC risk reduction was greater for diabetics without the comorbidities of cirrhosis, hepatitis B, hepatitis C, nonalcoholic fatty liver disease, end-stage renal disease, and hyperlipidemia, in the TZD cohort than in the non-TZD cohort. Male sex, cirrhosis, hepatitis B, and hepatitis C were significant independent factors predicting HCC (HRs of 1.43, 13.96, 2.31, and 2.15, respectively).

CONCLUSIONS:

This study suggests that the use of TZDs may reduce the risk of developing HCC among DM patients. Comorbidity with cirrhosis and/or hepatitis B/C infection appears to be associated with an extremely increased risk of developing HCC in this patient subset. These high-risk patients should be closely monitored.

KEYWORDS:

Thiazolidinediones (TZDs); cohort study; diabetes mellitus (DM); hepatocellular carcinoma (HCC); peroxisome proliferator activated receptor gamma (PPARĪ³)

PMID:
28744408
PMCID:
PMC5523039

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