AASLD2018[2079]噻唑烷二酮降低风险 肝细胞癌患者的肝细胞癌 慢

StephenW

s 2079
Thiazolidinediones Reduce the Risk of
Hepatocellular Carcinoma in Patients with
Chronic Hepatitis B and Diabetes Mellitus - a
Cohort Study of 29,221 Subjects
Cheuk Fung Yip1, Grace Lai2, Yee-Kit Tse1, Henry Lik Yuen
Chan2 and Vincent Wai Sun Wong2, (1)Institute of Digestive
Disease, and Department of Medicine and Therapeutics, The
Chinese University of Hong Kong, Hong Kong, (2)Institute of
Digestive Disease, Department of Medicine and Therapeutics,
and State Key Laboratory of Digestive Disease, The Chinese
University of Hong Kong, Hong Kong
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.

StephenW

2079年
噻唑烷二酮降低风险
肝细胞癌患者的肝细胞癌
慢性乙型肝炎和糖尿病 - a
29,221名受试者的队列研究
Cheuk Fung Yip1，Grace Lai2，Yee-Kit Tse1，Henry Lik Yuen
Chan2和Vincent Wai Sun Wong，（1）消化系统研究所
疾病，医学和治疗学系，
香港中文大学，香港，（2）香港中文大学
消化系统疾病，医学和治疗学系，
中国消化病国家重点实验室
香港大学，香港
背景：噻唑烷二酮（TZD）是一种成熟的产品
一类口服抗糖尿病药。它可以改善血糖控制
通过激活过氧化物酶体增殖物激活受体
γ（PPARγ）可改善胰岛素敏感性
和增强的葡萄糖代谢。 PPARγ的表达
也已显示可抑制肝细胞癌
（HCC）小鼠和体外模型中的细胞生长。我们研究了
TZD对全港队列中HCC风险的影响
慢性乙型肝炎（CHB）和糖尿病患者
（DM）。方法：1月份所有CHB和DM患者
2000年至2017年12月从医院确定
香港当局。 DM由空腹血浆定义
两次测量葡萄糖≥7mmol/ L或≥11.1mmol/ L.
一项测定，血红蛋白A1c（HbA1c）≥6.5％，使用抗糖尿病药
药物和/或胰岛素，或DM的诊断代码。我们
收集并分析患者人口统计数据，合并症，
药物，实验室检测结果，以及随后的
HCC的发展。使用TZD和其他药物
在随访期间将其建模为依赖于时间的协变量
在Cox比例风险模型中。血糖控制是
在随访期间通过时间加权平均值HbA1c进行总结。
我们排除了随访<6个月，肾脏的患者
替代疗法，估计肾小球滤过率
基线时<30 mL / min / 1.73 m2。结果：我们确定了29,221
CHB和DM患者; 2,703名患者（9.3％）发展
HCC在中位随访7。2年后（四分位数范围，
3.8-11.9岁）;随访期间有1,160名患者接受了TZD。
粗发病率（95％置信区间[CI]）
HCC治疗期间接受过TZD治疗的患者
随访时间为每1,000人4.8（2.3-8.8）和11.9（11.5-12.4）
人年分别。使用TZD可降低患病风险
HCC调整年龄，性别，肝硬化的存在，
实验室参数，使用其他抗糖尿病药物和
药物和核苷（酸）类似物（调整后的危害）
比率[aHR] 0.47,95％CI 0.22-0.98; P = 0.045）。在另一
手，二甲双胍的使用（aHR 0.74,95％CI 0.68-0.81;
P <0.001），他汀类药物（0.83,0.75-0.93; P <0.001），阿司匹林或
氯吡格雷（0.79,0.71-0.88; P <0.001）也降低了风险
HCC使用胰岛素（1.53,1.38-1.70; P <0.001）
和磺脲类（1.11,1.01-1.21; P = 0.023）增加
HCC的风险（表1）。结论：CHB患者
和DM一样，TZD的使用与降低风险有关
HCC。