Interpretation of the updated key points of the Guidelines for the diagnosis and treatment of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)

doi:10.19983/j.issn.2096-8493.2024162

Abstract

Abstract:

Anti-tuberculosis drug-induced liver injury (ATB-DILI) is the most common adverse drug reaction during anti-tuberculosis treatment and one of the common causes of DILI in China. In recent years, many new viewpoints and evidence have emerged in the research field of DILI. In view of this, the Tuberculosis Branch of the Chinese Medical Association organized relevant experts to update the Guidelines for the diagnosis and treatment of Anti-tuberculosis drug-induced liver injury (2019 Edition) and launched the Guidelines for the diagnosis and treatment of anti-tuberculosis drug-induced liver injury (2024 Edition). The authors compare and interpret the new and old versions of the ATB-DILI guidelines from seven aspects to help clinicians better understand and practice them.

Key words: Tuberculosis, Drug-induced liver injury, Guidelines

CLC Number:

Gu Jin, Lin Minggui, Tang Shenjie. Interpretation of the updated key points of the Guidelines for the diagnosis and treatment of drug-induced liver injury caused by anti-tuberculosis drugs (2024 version)[J]. Journal of Tuberculosis and Lung Disease , 2025, 6(2): 128-134. doi: 10.19983/j.issn.2096-8493.2024162

Figures/Tables 4

	推荐意见	推荐内容	证据及推荐级别
1	危险因素	NAT2慢乙酰化基因型和GSTM1基因变异、高龄、肝炎病毒感染或并发其他急慢性肝病、HIV感染、营养不良和酒精(乙醇)摄入是ATB-DILI的危险因素	2,B
2	R值计算	疑似ATB-DILI患者需计算R值,在病程中的不同时间计算R值,有助于准确判断DILI的临床类型及预后	2,C
3	完整的病史采集	既往用药史、临床特征、肝脏生化指标动态改变特点、药物再刺激反应、伴随疾病和基础肝病等	4,B
4	肝脏生化检查	至少包括ALT、AST、ALP、GGT、TBil、DBil、白蛋白,必要时测定凝血酶原时间或国际标准化比值(INR)	3,B
5	腹部影像学检查	疑似ATB-DILI患者应常规进行	3,B
6	肝脏活检组织学检查	有助于DILI的诊断和鉴别诊断	4,B
7	急性ATB-DILI的生化诊断阈值标准	肝脏生化检测需达到下列2个阈值标准之一:(1)ALT≥3×ULN和/或TBil≥2×ULN;(2)AST、ALP和TBil同时升高,且至少1项≥2×ULN	4,C
8	ATB-DILI的诊断标准	(1)有使用可能引起肝损伤的抗结核药物暴露史;(2)停药后异常肝脏生化指标迅速恢复:肝细胞损伤型患者血清ALT峰值水平在8d内下降>50%为高度提示,在30d内下降≥50%为重要提示;胆汁淤积型患者血清ALP或TBil峰值水平在180d内下降≥50%为重要提示;(3)排除其他病因或疾病所致的肝损伤;(4)再激发反应阳性。上述诊断标准中的3项符合即可确诊为ATB-DILI,(1)、(2)两项符合为疑似病例,实践的中的ATB-DILI绝大多数为疑似病例	3,B
9	再激发	对于造成严重肝损伤的药物,尽量避免再次应用	4,B
10	因果关系评估	推荐RUCAM量表作为因果关系评估的主要方法,在联合应用多个肝损伤抗结核药物、伴随基础肝病、新药临床试验等情况下,按照RUCAM量表评估ATB-DILI的可靠性会降低,建议结合专家意见进行因果关系评估	3,B
11	基线检测	建议所有患者在开始抗结核治疗前进行基线肝脏生化、HBsAg (如HBsAg阳性,进一步查HBV DNA)、抗-HCV检测,以及腹部影像学检查	3,B
12	监控频率	无高危因素者,建议每月监测1次肝脏生化指标; 有高危因素者或联合应用肝损伤药物者,在抗结核治疗的前2个月,每2周监测1次肝脏生物化学指标;其后每月监测1次	4,C 2,B
13	避免损伤肝脏药物同时应用	评估同时使用其他肝损伤药物,以及中药的获益风险比	4,C
14	抗病毒治疗	ATB-DILI患者并发病毒性肝炎,如具有抗病毒治疗指征,建议尽快给予抗病毒治疗	3,B
15	NAT2	可根据NAT2的基因多态性指导异烟肼剂量	4,C
16	预防性保肝治疗	存在肝损伤高危因素的人群可考虑; 不建议在普通人群中常规应用	4,C 2,B
17	立即停药	发生ATB-DILI应立即停用可疑药物	4,A
18	N-乙酰半胱氨酸(NAC)	早期静脉注射NAC有利于成人药物引起的急性肝衰竭(AHF)和亚急性肝衰竭(SAHF)	4,D
19	糖皮质激素	应谨慎使用,不能作为ATB-DILI的常规治疗; 可用于由免疫介导的伴有超敏和自身免疫特征的DILI	4,C 3,B
20	双环醇和/或异甘草酸镁	推荐应用于ALT/AST明显升高的急性肝细胞损伤型或混合型DILI	2,B
21	其他保肝药物的选择	对于ALT/AST升高的轻、中症肝细胞损伤型DILI,可合理选择甘草酸二铵、复方甘草酸苷等其他甘草酸类、谷胱甘肽、硫普罗宁、水飞蓟素类、多烯磷脂酰胆碱等药物; 对于ALP/GGT/TBil升高的胆汁淤积型DILI,可选择熊去氧胆酸或S-腺苷蛋氨酸; 不推荐2种或以上都以降低ALT为主的药物联合应用	4,C 4,C 4,B
22	重症患者的治疗	对药物性肝衰竭等重症患者,建议肝移植治疗; 人工肝(高容量血浆置换、双重血浆分子吸附系统等)可作为有益选择; 门冬氨酸鸟氨酸可能有助于降低重症或肝衰竭患者的血氨水平	2,B 4,C 4,C
23	恢复期的合理用药	在肝功能恢复中(后)应根据患者的肝损伤程度、有无肝损伤相关危险因素和结核病严重程度等进行综合判断,合理选择抗结核药物	4,C

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病因	相关实验室检查
甲型、乙型、丙型、戊型病毒性肝炎	抗-HAV(IgM);HBsAg、抗-HBc、HBV DNA;抗-HCV、HCV RNA;抗-HEV(IgM和IgG)、HEV RNA
CMV、HSV、EBV感染	抗-CMV、抗-HSV、抗-EBV的IgM和IgG
自身免疫性肝炎	ANA和ASMA滴度、IgG、IgA、IgM
原发性胆汁性胆管炎	AMA(尤其AMA-M2)滴度,IgG,IgA,IgM
酒精性肝病	饮酒史、GGT、MCV
非酒精性脂肪性肝病	超声或MRI
缺氧/缺血性肝病	急性或慢性充血性心衰、低血压、缺氧、肝静脉阻塞病史,超声或MRI
胆道疾病	超声或MRI,ERCP(视情况而定)
Wilson’s病	铜蓝蛋白
血色素沉着症	铁蛋白、转铁蛋白饱和度
α1-抗胰蛋白酶缺乏症	α1-抗胰蛋白酶

分级	ALT或ALP指标满足一项(ULN)		TBil (ULN)	临床表现/预后
分级	ALT	ALP	TBil (ULN)	临床表现/预后
1级(轻度)	≥3倍	≥2倍	<2倍
2级(中度)	≥5倍	≥2倍	≥2倍	可有肝炎症状
3级(重度)	≥5倍	≥2倍	≥2倍	可有肝炎症状并伴以下任意一项: INR≥1.5;腹腔积液和/或肝性脑病(病程<26周,且无肝硬化);DILI导致的其他器官功能衰竭
4级(致命)				因DILI死亡或需接受肝移植