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BMC Med:抗结核药物引起的肝损伤 哪些患者容易“中枪”?

2018-04-25 张琪 环球医学网

抗结核药物引起的肝损伤越来越引起人们的重视。2018年3月,发表在《BMC Med》的一项研究(REMoxTB研究)描述了因对肺结核治疗产生应答而使肝酶水平升高的患者的诱发因素的发生率和自然病史。

抗结核药物引起的肝损伤越来越引起人们的重视。2018年3月,发表在《BMC Med》的一项研究(REMoxTB研究)描述了因对肺结核治疗产生应答而使肝酶水平升高的患者的诱发因素的发生率和自然病史。

背景:药物诱导的肝损伤(DILI)是肺结核治疗的常见并发症。研究人员使用REMoxTB临床试验的数据描述因对肺结核治疗产生应答而使肝酶水平升高的患者的诱发因素的发生率和自然病史。

方法:患者接受标准肺结核治疗(2EHRZ/4HR)或4个月莫西沙星替换乙胺丁醇(异烟肼组,2MHRZ/2MHR)或异烟肼(乙胺丁醇组,2EMRZ/2MR)的方案。于0、2、4、8、12、17周测量肝酶,报告不良事件期间根据临床指征测量。患者入组标准为接受至少一次研究药物并且具有2次或更多次肝酶测量。

结果:总共纳入了1928例患者(2EHRZ/4HR组639例,2MHRZ/2MHR组654例,2EMRZ/2MR组635例)。DILI的定义为丙氨酸氨基转移酶(ALT)峰值水平≥5倍正常值上限(5×ULN)或ALT≥3×ULN且总胆红素>2×ULN。中位28天(四分位间距IQR,14~56),58/1928例患者(3.0%)出现DILI。标准肺结核治疗的639例患者(6.4%)中,41例出现临床显着的肝酶升高(ALT峰值≥3×ULN)。标准治疗下,21.1%的>55岁患者发生ALT/天门冬氨酸氨基转移酶(AST)峰值≥3×ULN(P=0.01),15%的HIV阳性患者发生ALT/AST峰值≥3×ULN,HIV阴性患者为9%(P=0.160)。与非异烟肼方案相比,包含异烟肼方案的中位ALT/AST峰值较高(P<0.05),与非莫西沙星相比,包含莫西沙星组的中位ALT/AST峰值较低(P<0.05)。接受异烟肼的患者比接受乙胺丁醇的患者达到ALT峰值≥3×ULN的时间早9.5天(中位时间为28 vs 18.5天)。67例ALT/AST峰值≥3×ULN的亚洲患者中,57例(85.1%)接受的是包含异烟肼的方案(P=0.008)。

结论:结果提供证据表明,标准治疗的肺结核患者具有DILI风险。标准治疗的老年患者、HIV阳性患者、亚洲患者和接受异烟肼的患者肝酶水平升高的风险较高。标准治疗的前2个月期间监测肝酶水平可检测约75%的肝酶峰值升高≥3×ULN的患者,表明这是一种标准治疗方法。这些结果提供证据表明,莫西沙星在保肝中的应用前景。

原始出处:
Tweed CD, Wills GH, Crook AM, et al.Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.BMC Med. 2018 Mar 28;16(1):46. doi: 10.1186/s12916-018-1033-7.

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  7. 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channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78629, encryptionId=f30ae86297d, topicName=结核)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4dfa37, createdName=huhuaidong387, createdTime=Fri Apr 27 04:46:00 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1338781, encodeId=8e7b1338e814c, content=<a href='/topic/show?id=9d3d812280b' target=_blank style='color:#2F92EE;'>#肝损伤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=64, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81228, encryptionId=9d3d812280b, topicName=肝损伤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=8e886, createdName=仁者大医, createdTime=Fri Apr 27 04:46:00 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1397525, encodeId=fe6c139e52567, content=<a 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Wed Apr 25 14:16:47 CST 2018, time=2018-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309172, encodeId=8e193091e298, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Wed Apr 25 14:06:35 CST 2018, time=2018-04-25, status=1, ipAttribution=)]
    2018-04-27 wgx309
  8. 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Wed Apr 25 14:16:47 CST 2018, time=2018-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309172, encodeId=8e193091e298, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Wed Apr 25 14:06:35 CST 2018, time=2018-04-25, status=1, ipAttribution=)]
  9. 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authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Wed Apr 25 14:16:47 CST 2018, time=2018-04-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309172, encodeId=8e193091e298, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/09/07/a9772c74ffd6edc03a7f9af07b4747f6.jpg, createdBy=b3722138742, createdName=sunfeifeiyang, createdTime=Wed Apr 25 14:06:35 CST 2018, time=2018-04-25, status=1, ipAttribution=)]
    2018-04-25 王秀

    学习了.涨知识了!

    0

  10. 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    2018-04-25 sunfeifeiyang

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