Aliment Pharm Ther:多学科讨论:慢性病毒性肝炎患者使用他汀获益大

2017-12-26 吴星 环球医学

病毒性肝炎是全球死亡的主要原因,2013年造成约145万人死亡。2017年11月,发表在《Aliment Pharmacol Ther》的一项由香港科学家进行的倾向评分加权的界标分析表明,他汀可降低慢性病毒性肝炎患者肝脏失代偿和死亡风险。

病毒性肝炎是全球死亡的主要原因,2013年造成约145万人死亡。2017年11月,发表在《Aliment Pharmacol Ther》的一项由香港科学家进行的倾向评分加权的界标分析表明,他汀可降低慢性病毒性肝炎患者肝脏失代偿和死亡风险。请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——

背景:因门静脉高压造成的失代偿性肝病可导致显着性高的发病率和死亡率。他汀可调节肝内血管张力,但是临床意义仍不确定。

目的:旨在确定慢性病毒性肝炎患者中,他汀对肝脏失代偿和死亡风险的影响。

方法:研究者使用香港医管局中基于医院的数据库进行了一项全人群队列研究。通过国际疾病分类第九版临床改良版的诊断编码鉴别出2000~2012年无既往肝脏失代偿的慢性病毒性肝炎患者。他汀使用定义为累积限定日剂量为>28。界标分析用于去除恒定时间偏倚。研究者进行了进一步的倾向评分加权来将基线混杂因素最小化。首要结局为门静脉高压相关的肝脏失代偿事件的复合,并调整了死亡作为竞争风险。

结果:总共69184例慢性病毒性肝炎患者(他汀使用者2053人,非使用者67131人)纳入到2年的界标分析中。对23个基线协变量进行倾向评分加权后,相对于不使用他汀,他汀与复合性肝功能失代偿事件的显着减少(HR:0.55;95% 置信区间[CI]:0.36~0.83;P=0.005)、腹水(HR:0.57;95% CI:0.36~0.92;P=0.02)和死亡的剂量依赖性减少(HR:0.87;95% CI:0.76~0.99;P=0.035)相关。

结论:倾向评分加权界标分析显示,与不使用他汀相比,使用他汀的慢性病毒性肝炎患者的肝功能失代偿和死亡风险降低。

多学科讨论记实:

此倾向评分加权界标分析显示,地域广泛的患者队列(主要感染慢性乙肝)中他汀的使用,与新发作复合肝脏失代偿风险降低45%和死亡风险降低13%独立相关。他汀代表慢性肝病患者中潜在的预后改良药物,给予当前有限的可及治疗以重要贡献。研究者的发现可能由他汀对门静脉高压的多效作用来解释。除了肝硬化导致的结构变形,已确定一氧化氮合成酶中的肝内皮功能障碍和合成损伤作为肝内血流阻力的重要因素。在动物模型和人体机理研究中,他汀已显示出通过PI3K/Akt通路在Ser 1177/1179中通过上调内皮型一氧化氮合酶(eNOS)磷酸化作用来改善eNOS表达和活动,增强eNOS和其刺激辅因子Hsp90之间的相关性,并抑制eNOS抑制蛋白小窝蛋白-1。肝脏一氧化氮的合成增加反过来使肝抵抗性降低,改善血管舒张,且通过吲哚菁绿清除增强反映肝功能改善。在一氧化氮独立通路中,他汀也能通过RhoA/Rho-激酶抑制肝星状细胞收缩。

本研究有一些局限性。无法单独确定肝病的严重程度,因为数据库不包括AST值,因此不能计算APRI和FIB-4评分。然而,由于研究者特别想评估新发肝失代偿的风险,有既往肝失代偿事件的患者被系统性排除。纳入的患者应一律有更轻微形式的慢性肝病。本研究中超过85%的他汀处方为辛伐他汀,不能确定他汀类型的差异影响。近期一项感染丙肝的退伍军人研究发现,与其他他汀(如普伐他汀和辛伐他汀)相比,阿托伐他汀和氟伐他汀带来FIB-4评分更大程度的降低。然而,在一项2009年的随机对照试验中,辛伐他汀已显示出能降低门静脉高压。研究者不能排除医院系统之外服用处方他汀的患者的可能性。尽管分析涉及约70000人,他汀使用者中相对少的复合失代偿事件使得无法考察剂量反应关系。研究可以显示,他汀使用>385 cDDD与更少的总死亡率相关。注册不能确定死因,有病毒性肝炎的肝硬化的死亡率最近证实为抓哟是肝脏相关原因,比如静脉曲张和肝细胞癌。

原始出处:

Wong JC, Chan HL, Tse YK, et al. Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis. Aliment Pharmacol Ther. 2017 Nov;46(10):1001-1010. doi: 10.1111/apt.14341. Epub 2017 Sep 21.

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    2018-07-25 howi
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    2018-08-10 jj000001
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