背景：非甾体类抗炎药(NSAIDs)已经被证实可以减轻炎症和多种肿瘤的患病风险，然而，它们对于肝细胞癌的患病风险及由于慢性肝病所导致的死亡的影响，目前尚无相关研究。方法：我们前瞻性的对美国国立卫生研究院退休人员分析协会饮食与健康研究调查组中的300504名参与者（年龄50-71岁）进行调查，同时对与确诊为肝细胞癌(n=250)和慢性肝病死亡(n=428, 除外HCC)相关的，经本人描述的,阿司匹林和非阿司匹林类非甾体类抗炎药服用史进行分析。使用经年龄、性别、种族，吸烟，饮酒，糖尿病及BMI进行校正后的Cox比例风险回归模型，计算患者的风险率比值和双侧的95%可信区间，所有的统计学意义都是以双侧的形式表示。结果：与未服用阿司匹林者相比，服用阿司匹林明显的降低了肝细胞癌的发生风险(RR = 0.59; 95% CI = 0.45 to 0.77)和慢性肝病所导致的死亡率(RR = 0.55; 95% CI = 0.45 to 0.67)。相比而言,服用非阿司匹林类的NSAIDs类药物的人群与未服药者相比，仅降低了慢性肝病所导致的死亡率(RR = 0.74; 95% CI= 0.61 to 0.90)，而没有降低肝癌的发生风险。风险评价的统计学意义在经过服药频率进行调整后（次/月，次/周，次/天）没有出现变化，但是在根据月服药次数进行调整后，与未服药者相比，使用非阿司匹林类NSAID药物的人群可以降低慢性肝病所导致的死亡率。结论：服用阿司匹林与肝细胞癌的发生率及慢性肝病所导致的病死率的降低相关，而服用非阿司匹林的非甾体抗炎药只与慢性肝病导致的死亡率的降低具有相关性。
吉林大学第一医院肝胆胰内科 张明媛 牛俊奇 摘译
本文首次发表于[J Natl Cancer Inst, 2012, 104(23):1808-1814]
Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.Methods: We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health-AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.Methods: We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health-AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass i. Results： Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users. Conclusions：Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.
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