Hepatology:质子泵抑制剂(PPI)的长期服用能够增加胆道癌的发病率:来自瑞典人群队列研究结果

2021-05-22 yd2015 MedSci原创

长期的服用质子泵抑制剂(PPI)能够增加胆道癌的发病率。

胆道癌是一组特异性较强的恶性肿瘤,约占胃肠道肿瘤的3%。大多数患者诊断时已是晚期,5年生存率约为2%-24%。慢性乙型、丙型病毒性肝炎、胆结石、肝吸虫、原发性硬化性胆管炎等被认为是胆道癌的危险因素。质子泵抑制剂(PPI)是常用的抑酸剂,已有研究表明长期应用PPI跟胃癌胰腺癌的发病有关。PPI的长期使用跟胆管炎有关。但是,很少研究评估PPI使用跟胆道癌的关系。近期,来自瑞典的研究团队在Hepatology杂志上发表了一项研究成果,发现PPI的长期服用增加患胆道癌的危险性。

研究收集2005至2012年期间服用PPI的患者信息和计算胆道癌的发病率。PPI暴露(长期使用)定义为PPI服用≥180天。根据总体以及亚组(比如年龄、性别、年限、PPI使用的适应征等)计算其标准化发病率(SIRs)和95%CI。一共738881患者服用PPI,其中 57.2%为女性, 42.8%为男性,55.4%患者大于60岁。其中64%患者服用PPI的原因为长期服用阿司匹林和非甾体抗炎药(NSAIDS)。48%患者伴有胃食管反流和消化道溃疡病变。

中位随访5.3年(IQR 2.8-7.1),206 (0.03%)发展为胆囊癌,标准化发病率(SIRs)为1.58 (95% CI 1.37-1.81);265 (0.04%) 发展为肝外胆管癌,SIRs为1.77 (95% CI 1.56-2.00) 和 131 (0.02%)发展为肝内胆管癌,SIRs为1.88 (95% CI 1.57-2.23)。50,123例伴有胆结石患者中, 95 (0.2%) 发展为胆囊癌, 58 (0.12%)肝外胆管癌,19 (0.04%) 发展为肝内胆管癌。65,046例伴有胆结石、或慢性肝和或胰腺疾病等患者中,103 (0.16%)发展为胆囊癌, 81 (0.12%)发展为肝外胆管癌,38 (0.06%) 发展为肝内胆管癌。

肝内胆管癌的发病率在女性(SIR=1.85, 95%CI 1.45-2.33)中较男性(SIR=2.06, 95% CI 1.50-2.76)高。而肝内胆管细胞癌发病率在男性(SIR=2.06, 95% CI 1.50-2.76)中较女性(SIR=1.93, 95% CI 1.46-2.51)要高。所有三种类型胆道癌的发病率随着年龄的增长而降低。

        PPI长期服用对年龄、性别、服用时间等分组比较发病率

对PPI服用的适应症进行分组时,胆囊癌的发病率在阿司匹林组为SIR=1.29, 95% CI 0.85-1.88,胃十二指肠炎(SIR=2.06, 95% CI 1.45-2.84) ,NSAIDS治疗组 (SIR=2.06, 95% CI 1.41-2.91)。肝外胆道癌发病率在胃食管反流组最高(SIR=3.07, 95% CI 2.34-3.96) ,而在阿司匹林组最低 (SIR=1.80, 95% CI 1.27-2.46)。肝内胆道癌除了胃食管反流组(SIR=0.63, 95% CI 0.41-0.93) 和 NSAIDS 组(SIR=1.74, 95% CI 0.97-2.87)没有明显增加发病率,其他组均增加发病率。

第一年的PPI持续使用, 胆囊癌的SIR为1.74 (95% CI 1.29–2.29), 肝外胆道癌SIR为2.89 (95% CI 2.32-3.54) 和肝内胆道癌SIR为3.36 (95% CI 2.43-4.52)。≥ 5 年PPI 的服用, 胆囊癌的SIR =1.48;95% CI 1.06-2.02, 肝外胆道管SIR = 1.44;95% CI 1.06- 1.91,肝内胆道癌的SIR=1.84; 95% CI 1.25-2.61)

       对PPI适应症分组分析发病率

18,849例长期服用H2受体抑制剂(H2RA), 只有 3例发展为胆囊癌, 4 例发展为肝外胆道癌,2例发展为肝内胆道癌。H2RA服用者的肿瘤发病人数太少而不能计算SIRs。

综上,研究表明,长期的服用质子泵抑制剂(PPI)能够增加胆道癌的发病率。

原始出处:

Habiba Kamal, Omid Sadr-Azodi, Lars Engstrand, et al. Association between Proton Pump Inhibitor Use and Biliary Tract Cancer Risk: a Swedish Population-Based Cohort Study. Hepatology. 2021 May 21.  doi: 10.1002/hep.31914.  Online ahead of print.

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    2023-02-24 ms2000000182667314

    学习了

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    2022-03-03 jklm09
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    2021-05-24 gwc384
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    2021-05-22 smart Ren

    认真学习

    0

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