阿司匹林对病毒性肝炎患者肝癌发生率影响的Meta分析
DOI: 10.3969/j.issn.1001-5256.2021.05.024
Effect of aspirin on the incidence rate of liver cancer in patients with viral hepatitis: A Meta-analysis
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摘要:
目的 评价阿司匹林的使用对病毒性肝炎患者肝癌发生率的影响。 方法 检索PubMed、Web of Science、Cochrane Library英文数据库,收集建库至2020年7月15日关于病毒性肝炎患者使用阿司匹林与肝癌发生率的研究。选择风险比(HR)和95%CI作为汇总指标。用RevMan 5.3进行Meta分析、对不能合并的数据采用描述性分析。 结果 共纳入9篇文献,涉及132 066例病毒性肝炎患者。结果表明使用阿司匹林的病毒性肝炎患者肝癌发生率降低31%(HR=0.69,95%CI: 0.65~0.74,P<0.000 01);4项研究报道了消化道出血发生率,表明使用阿司匹林未显著增加病毒性肝炎患者消化道出血风险(P>0.05)。 结论 接受阿司匹林治疗可能有利于降低病毒性肝炎患者肝癌发生率,未显著增加包括肝硬化人群在内的消化道出血风险,对于减少肝癌的发生可能具有积极意义,但该临床现象背后的机制尚不明确,且仍需更多临床观察以验证其安全性和有效性。 -
关键词:
- 肝炎, 病毒性, 人 /
- 阿司匹林 /
- 癌, 肝细胞 /
- Meta分析(主题)
Abstract:Objective To evaluate the effect of the use of aspirin on the incidence rate of liver cancer in patients with viral hepatitis. Methods English databases including PubMed, Web of Science, and Cochrane Library were searched for studies on the use of aspirin and the incidence rate of liver cancer in patients with viral hepatitis published up to July 15, 2020. Hazard ratio (HR) and 95% confidence interval (CI) were selected as pooled indicators. RevMan 5.3 was used to perform the Meta-analysis, and a descriptive analysis was performed for data that could not be pooled. Results Nine studies were included, involving 132 066 patients with viral hepatitis. The results showed that the incidence rate of liver cancer was reduced by 31% in the patients with viral hepatitis who were treated with aspirin (HR=0.69, 95% CI: 0.65-0.74, P < 0.000 01). Four studies reported the incidence rate of gastrointestinal bleeding, suggesting that the use of aspirin did not significantly increase the risk of gastrointestinal bleeding in patients with viral hepatitis(P > 0.05). Conclusion Aspirin therapy may help to reduce the incidence rate of liver cancer in patients with viral hepatitis and does not significantly increase the risk of gastrointestinal bleeding in such patients and the patients with liver cirrhosis. Aspirin may have a positive significance in reducing liver cancer, but the mechanism behind this clinical phenomenon remains unclear, and therefore, more clinical observation studies are needed to verify its safety and efficacy. -
Key words:
- Hepatitis, Viral, Human /
- Aspirin /
- Carcinoma, Hepatocellular /
- Meta-Analysis as Topic
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表 1 Meta分析纳入文献的基本特征
纳入研究 地区 研究类型 随访时间 阿司匹林使用定义 随访人数 人群 Simon等[21](2020) 瑞典 队列研究 中位随访期7.9年 低剂量(75 mg或160 mg),≥90 DDDs 50 275 HBV/HCV Liao等[22](2020) 中国台湾 队列研究 最长随访期≥12年 NA 3822 HCV Wu等[23](2020) 中国台湾 队列研究 最长随访期≥5年 ≥90 DDDs 9417 HCV Lee等[24](2020) 中国台湾 队列研究 最长随访期≥5年 规律用药≥90 d 7434 HCV Lee等[25](2019) 中国台湾 队列研究 最长随访期≥5年 规律用药≥90 d 10 615 HBV Simon等[26](2019) 瑞典 队列研究 中位随访期8.5年 剂量<162 mg且≥30 DDDs 18 368 HBV/HCV Du等[27](2019) 中国 队列研究 中位随访期4.5年 术后7 d内开始服用,剂量为100 mg/d且持续≥1年 264 HBV/HCV Hwang等[28](2018) 韩国 队列研究 中位随访期4年 ≥30 DDDs 31 528 病毒性肝炎 Lee等[29](2017) 韩国 队列研究 中位随访期38.5个月 100 mg/d,使用时间≥6个月 343 HBV 纳入研究 是否包含肝硬化人群 是否抗病毒治疗 匹配或调整变量 报告结局 NOS评分 Simon等[21](2020) 是。对照组14.2%,阿司匹林组13.6% 是。对照组31.7%,阿司匹林组29.2% 倾向性评分;2~8 ①② 9 Liao等[22](2020) 是。NA 否 倾向性评分;1、2、5~7 ① 9 Wu等[23](2020) 是。NA 是。对照组5.4%,阿司匹林组5.5% 倾向性评分;1、2、4~8 ① NA Lee等[24](2020) 是。对照组15.1%,阿司匹林组16.0% 是。对照组4.7%,阿司匹林组5.4% 倾向性评分;1、2、4~8 ①② 9 Lee等[25](2019) 是。对照组17.1%,阿司匹林组17.1% 是。对照组15.8%,阿司匹林组15.8% 倾向性评分;1~3、5~8 ①② 9 Simon等[26](2019) NA NA 倾向性评分;NA ① NA Du等[27](2019) 是。对照组100%,阿司匹林组100% NA NA ① 7 Hwang等[28](2018) NA NA 1、2、7、8 ① 8 Lee等[29](2017) 是。阿司匹林组12.2% 否 倾向性评分;1、5、8 ①② 8 注:调整变量1~8分别为1,年龄;2,性别;3,抗HBV治疗;4,抗HCV治疗;5,肝硬化;6,其他药物(如二甲双胍、他汀类等具有潜在化学预防肝癌药物);7,合并症;8,其他。报告结局包括①肝癌发生率;②消化道出血发生率。DDDs,限定日剂量。NA, 未提及。 表 2 亚组分析
亚组 研究数目 HR(95%CI) P值 I2值(%) P值 地域 东方[22-25, 27-29] 7 0.67(0.58~0.78) <0.000 1 50 0.04 西方[21, 26] 2 0.68(0.62~0.74) <0.000 1 0 0.63 肝炎类型 HBV[25, 29] 2 0.49(0.19~1.27) 0.14 70 0.07 HCV[22-24] 3 0.72(0.59~0.87) <0.000 1 60 0.08 混合病例[21, 26-28] 4 0.67(0.62~0.73) <0.000 1 20 0.28 人群 抗病毒治疗[23-25] 3 0.68(0.42~1.09) 0.11 46 0.16 肝硬化[23-25, 27] 4 0.77(0.58~1.02) 0.07 53 0.09 匹配或调整变量 抗病毒治疗[21, 23-25] 4 0.73(0.67~0.78) <0.000 1 0 0.49 肝硬化[21-25, 29] 6 0.71(0.66~0.76) <0.000 1 46 0.10 -
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