抗结核药所致药物性肝损伤诊断与处理专家建议原版.pptx

1、抗结核药所致药物性肝损伤诊断与处理 专家建议2013,定义,临床分型,临床表现,相关危险因素,发生机制,诊断,处理,发生率,目录,在结核病抗结核治疗过程中可能会出现各种不同程度的药物不良反应，其中以抗结核药所致药物性肝损伤（drug-induced liver injury，DILI）最为多见，危害性最大，也是我国DILI的常见类型之一,部分患者因此不得不中止抗结核治疗从而影响结核病的治疗效果临床医生应高度重视这个问题,轻者 表现为一过性转氨酶升高,重者 可致肝衰竭,甚至危及生命,概述,抗结核药所致DILI是指在使用抗结核药过程中，由于药物或其代谢产物引起的肝细胞毒性损伤或肝脏对药物及其代谢产

2、物的变态反应所致病理过程。,可以表现为无症状丙氨酸转氨酶（ALT）升高，也可呈急性肝炎表现，甚至发生暴发性肝细胞坏死，少数患者可表现为慢性肝炎,ALT2倍正常值上限（ULN）或结合胆红素2倍ULN；或天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）和总胆红素同时升高，且至少1项2倍ULN,一、抗结核药所致DILI的定义,各国报告的抗结核药所致DILI发生率不同，这种差别可能与以下四个因素有关,研究的标准,地理位置,社会经济状况,种族,研究者对DILI的诊断标准、病毒性肝炎的流行预防性保肝治疗和研究对象不同等因素有关,二、抗结核药所致DILI的发生率,印度的抗结核药所致DILI发生率较高（8%10

3、%）,西方国家较低美国15 d （+1分）停药时间15 d （+1分）（2）撤药反应：药后8 d内ALT从峰值下降50% （+3分）停药后30 d内ALT从峰值下降50% （+2分）停药30 d后ALT从峰值下降50% （0分）停药30 d后ALT峰值下降2倍ULN （+2分）可疑阳性：再用药后ALT升高2倍ULN，同时合并使用其他药物 （+1分）阴性：再用药后ALT升高8分为极有可能，68分为很可能有关，35分为可能有关，12分为可能无关，0分为无关,七、抗结核药所致DILI的诊断,七、抗结核药所致DILI的诊断,七、抗结核药所致DILI的诊断,保证患者抗结核治疗的顺利完成,正确的处理,及时

4、纠正肝功能异常逆转肝功能损伤,本共识仅介绍原则性问题的处理，提供5点参考,八、抗结核药所致DILI的处理,八、抗结核药所致DILI的处理,治疗前应综合评估患者的 结核病病情、肝损伤程度、相关危险因素及全身状况等,仅ALT3倍ULN，无明显症状、无黄疸 可在密切观察下保肝治疗并酌情停用肝损伤发生频率高的抗结核药物,ALT3倍ULN，或总胆红素2ULN应停用有关抗结核药物，保肝治疗，密切观察,ALT5倍ULN，或ALT3倍ULN伴有黄疸、恶心、呕吐、 乏力等症状，或总胆红素3倍ULN 应立即停用所有抗结核药物，积极保肝治疗 严重肝损伤患者应住院采取综合治疗措施有肝功能衰竭表现时应积极采取抢救措施。

5、,No.1,No.2,No.3,No.4,八、抗结核药所致DILI的处理,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可减少DILI的发生。,3,2,6,5,1,4,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可减少DILI的发生。,3,2,6,5,4,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可减少DILI的发生。,3,6,5,4,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可

6、减少DILI的发生。,6,5,4,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可减少DILI的发生。,6,5,八、抗结核药所致DILI的处理,抗结核药所致DILI是影响抗结核治疗成败的重要因素之一，有效的预防可减少DILI的发生。,6,八、抗结核药所致DILI的处理,八、抗结核药所致DILI的处理,01,02,03,04,05,06,07,08,八、抗结核药所致DILI的处理,八、抗结核药所致DILI的处理,肝功能恢复中和恢复后如何应用抗结核药物，国内外均无统一的规定和标准 对于这个问题本专家组认为，应根据患者的肝损伤程度、有无肝损伤相关危

7、险因素和结核病严重程度等进行综合判断，并参考ATS建议、英国胸科学会指南提出以下几点建议,八、抗结核药所致DILI的处理,抗结核药所致药物性肝损伤诊断与处理的专家建议,对于仅表现为单纯ALT升高的肝损伤患者 待ALT降至3倍ULN时，可加用链霉素或阿米卡星、异烟肼和乙胺丁醇，每周复查肝功能，若肝功能进一步恢复则加用利福平或利福喷丁，待肝功能恢复正常后，视其基础肝脏情况等考虑是否加用吡嗪酰胺,对于肝损伤合并过敏反应（同时有发热、皮疹等）的患者 待机体过敏反应全部消退后再逐个试用抗结核药物，试药原则：可先试用未曾用过的药物，此后按照药物致敏可能性由小到大逐步试药,对于ALT升高伴有总胆红素升高或黄

8、疸等症状的患者 待ALT降至3倍ULN及总胆红素2倍ULN时，可加用链霉素或阿米卡星、乙胺丁醇和氟喹诺酮类药物，若肝功能进一步恢复则加用异烟肼，待肝功能恢复正常后，视其结核病严重程度及基础肝脏情况等考虑是否加用利福喷丁或吡嗪酰胺,八、抗结核药所致DILI的处理,大部分抗结核药所致DILI患者经过正确、及时的治疗可以治愈，仅有少数患者发展成肝功能衰竭，严重者可致死亡，病死率报道不一,对氨基水杨酸钠过敏反应者如不及时停药可发生重症肝炎，病死率可达21%。溶血进行性加重者的病死率更高,年龄、性别、ALT升高水平、HIV或HBV感染并不影响抗结核药所致DILI的预后，而抗结核治疗时间、肝性脑病和腹水、

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