Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Kangwon National University Hospital, Chuncheon, Korea.
Hepatology. 2017 Nov;66(5):1556-1569. doi: 10.1002/hep.29318. Epub 2017 Sep 29.
Antiplatelet therapy has shown protective effects against hepatocellular carcinoma (HCC) in preclinical studies. However, it is unclear whether antiplatelet therapy lowers the risk of HCC in patients with chronic hepatitis B. A retrospective analysis was conducted of data from 1,674 chronic hepatitis B patients, enrolled between January 2002 and May 2015, whose serum hepatitis B virus DNA levels were suppressed by antivirals to <2,000 IU/mL. The primary and secondary outcomes were development of HCC and bleeding events, respectively. Risk was compared between patients with antiplatelet treatment (aspirin, clopidogrel, or both; antiplatelet group) and patients who were not treated (non-antiplatelet group) using a time-varying Cox proportional hazards model for total population and propensity score-matching analysis. The antiplatelet group included 558 patients, and the non-antiplatelet group had 1,116 patients. During the study period, 63 patients (3.8%) developed HCC. In time-varying Cox proportional analyses, the antiplatelet group showed a significantly lower risk of HCC (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.23-0.85; P = 0.01), regardless of antiplatelet agent. In propensity score-matched pairs, antiplatelet therapy significantly reduced the risk of HCC (HR, 0.34; 95% CI, 0.15-0.77; P = 0.01). However, the overall risk of bleeding was higher in the antiplatelet group (HR, 3.28; 95% CI, 1.98-5.42; P < 0.001), particularly for clopidogrel with or without aspirin. Treatment with aspirin alone was not associated with a higher bleeding risk (HR, 1.11; 95% CI, 0.48-2.54; P = 0.81).
Antiplatelet therapy reduces the risk of HCC in chronic hepatitis B patients whose hepatitis B virus is effectively suppressed. However, antiplatelet therapy containing clopidogrel may increase the risk of bleeding. (Hepatology 2017;66:1556-1569).
抗血小板治疗已在临床前研究中显示出对肝细胞癌(HCC)的保护作用。然而,尚不清楚抗血小板治疗是否会降低慢性乙型肝炎患者发生 HCC 的风险。
对 2002 年 1 月至 2015 年 5 月期间入组的 1674 例慢性乙型肝炎患者的数据进行回顾性分析,这些患者的血清乙型肝炎病毒 DNA 水平通过抗病毒治疗抑制至<2000IU/mL。主要和次要结局分别为 HCC 的发生和出血事件。使用总人群的时间变化 Cox 比例风险模型和倾向评分匹配分析比较抗血小板治疗(阿司匹林、氯吡格雷或两者联合;抗血小板组)和未治疗患者(非抗血小板组)之间的风险。抗血小板组包括 558 例患者,非抗血小板组有 1116 例患者。在研究期间,有 63 例(3.8%)患者发生 HCC。在时间变化的 Cox 比例风险分析中,抗血小板组 HCC 的风险显著降低(风险比 [HR],0.44;95%置信区间 [CI],0.23-0.85;P=0.01),而与抗血小板药物无关。在倾向评分匹配的对中,抗血小板治疗显著降低 HCC 的风险(HR,0.34;95%CI,0.15-0.77;P=0.01)。然而,抗血小板组的总体出血风险更高(HR,3.28;95%CI,1.98-5.42;P<0.001),尤其是氯吡格雷联合或不联合阿司匹林。单独使用阿司匹林治疗与较高的出血风险无关(HR,1.11;95%CI,0.48-2.54;P=0.81)。
抗血小板治疗可降低乙型肝炎病毒有效抑制的慢性乙型肝炎患者 HCC 的风险。然而,含氯吡格雷的抗血小板治疗可能会增加出血风险。