Thiazolidinediones Reduce the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B and Diabetes Mellitus - a Cohort Study of 29,221 Subjects
Refereed conference paper presented and published in conference proceedings



摘要Background: Thiazolidinedione (TZD) is a well-established class of oral anti-diabetic agents. It improves glycemic control by activating peroxisome proliferator-activated receptor gamma (PPARγ) that leads to improved insulin sensitivity and enhanced glucose metabolism. Expression of PPARγ has also been shown to suppress hepatocellular carcinoma (HCC) cell growth in mice and in vitro models. We studied the impact of TZD on the risk of HCC in a territory-wide cohort of patients with chronic hepatitis B (CHB) and diabetes mellitus (DM).

Methods: All patients with CHB and DM from January 2000 to December 2017 were identified from the Hospital Authority, Hong Kong. DM was defined by fasting plasma glucose ≥7mmol/L in two measurements or ≥11.1mmol/L in one measurement, hemoglobin A1c (HbA1c) ≥6.5%, use of antidiabetic drugs and/or insulin, or diagnosis codes of DM. We collected and analyzed patient demographics, comorbidities, medications, laboratory test results, and subsequent development of HCC. The use of TZD and other medications during follow-up were modelled as time dependent covariates in Cox proportional hazards model. Glycemic control was summarized by time-weighted mean HbA1c during followup. We excluded patients with follow-up <6 months, renal replacement therapy, and estimated glomerular filtration rate <30 mL/min/1.73 m2 at baseline.

Results: We identified 29,221 patients with CHB and DM; 2,703 patients (9.3%) developed HCC after a median follow-up of 7.2 years (interquartile range, 3.8–11.9 years); 1,160 patients received TZD during followup. The crude incidence rates (95% confidence interval [CI]) of HCC in patients who did and did not receive TZD during follow-up were 4.8 (2.3–8.8) and 11.9 (11.5–12.4) per 1,000 person-years, respectively. Use of TZD reduced the risk of HCC after adjustment of age, gender, presence of cirrhosis, laboratory parameters, use of other anti-diabetic agents and medications, and nucleos(t)ide analogues (adjusted hazard ratio [aHR] 0.47, 95% CI 0.22–0.98; P=0.045). On the other hand, the use of metformin (aHR 0.74, 95% CI 0.68–0.81; P<0.001), statins (0.83, 0.75–0.93; P<0.001), and aspirin or clopidogrel (0.79, 0.71–0.88; P<0.001) also reduced the risk of HCC, whereas the use of insulin (1.53, 1.38–1.70; P<0.001) and sulfonylureas (1.11, 1.01–1.21; P=0.023) increased the risk of HCC (Table 1).

Conclusion: In patients with CHB and DM, the use of TZD is associated with a lower risk of HCC.
著者Terry Cheuk-Fung Yip, Grace Lai-Hung Wong, Yee-Kit Tse, Henry Lik-Yuen Chan, Vincent Wai-Sun Wong
會議名稱The American Association for the Study of Liver Diseases (AASLD) Liver Meeting 2018
會議地點San Francisco
期次Suppl 1
頁次1185A - 1185A

上次更新時間 2020-03-08 於 06:37