抗结核药所致药物性肝损伤诊治指南(2024年版)  

Guidelines for diagnosis and management of drug-induced liver injury caused by anti-tuberculosis drugs(2024 version)

作　　者：中华医学会结核病学分会 顾瑾[2] 林明贵 唐神结[4] Chinese Medical Association Tuberculosis Branch;Gu Jin;Lin Minggui;Tang Shenjie(不详;Shanghai Pulmonary Hospital,Tongji University School of Medicine,Shanghai 200433,China;Center for Infectious Diseases,Beijing Tsinghua Chang Gung Hospital,Tsinghua University,Beijing 102218,China;Institute of Tuberculosis and Thoracic Tumor,Beijing Chest Hospital,Capital Medical University,Beijing 101149,China)

机构地区：[1]不详 [2]同济大学附属上海市肺科医院,上海市结核病临床研究中心,上海200433 [3]清华大学附属北京清华长庚医院感染疾病中心,北京102218 [4]首都医科大学附属北京胸科医院,北京市结核病胸部肿瘤研究所,北京101149

出　　处：《中华结核和呼吸杂志》2024年第11期1069-1090,共22页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家重点研发计划(2023ZX10003001);上海市加强公共卫生体系建设三年行动计划(2023-2025);重点学科项目(GWVI-11.1-05)。

摘　　要：药物性肝损伤是患者抗结核治疗过程中最常见的药物不良反应之一,为提高临床医师及结核病防控工作者对抗结核药所致药物性肝损伤(anti-tuberculosis drug-induced liver injury,ATB-DILI)的正确诊断和处理能力,中华医学会结核病学分会于2013年组织相关专家制定了《抗结核药所致药物性肝损伤诊断与处理专家建议》,2019年对该建议进行了更新,形成了《抗结核药所致药物性肝损伤诊治指南(2019年版)》,上述建议和指南的出台对规范我国ATB-DILI的诊治以及提升临床处理能力起到了重要的指导作用。根据全球近年来的相关领域研究进展,更新现有的文献证据,中华医学会结核病学分会对指南进行修订和更新,形成了《抗结核药所致药物性肝损伤诊治指南(2024年版)》。本次指南更新内容主要包括以下几个方面:(1)流行病学:ATB-DILI发生率全球呈现明显的上升趋势,我国为9.5%~14.1%。(2)危险因素:强调减少或避免其他损害肝脏药物的合并应用,中药的合并应用需评估获益与风险。(3)发生机制:可分为固有型、特异质型和间接型。ATB-DILI的发生与多种机制相关。(4)ATB-DILI的诊断:提出肝脏生化诊断阈值标准仅适用于急性DILI的诊断,不适用于慢性和特殊表型DILI的诊断。伴基础肝病患者,当转氨酶较基线水平升高1倍或肝脏生化指标显著恶化无法用基础肝病解释时,应怀疑DILI的可能性。在RUCAM量表的应用基础上,建议结合专家意见进行因果关系评估,避免误诊及漏诊。(5)ATB-DILI的严重程度分级:调整为4级。(6)保肝药物:推荐根据ATB-DILI的肝损伤类型应用保肝药物。(7)抗结核药物:环丝氨酸和利奈唑胺可在不能组成有效抗结核治疗方案时应用;对于合并基础肝病或其他疾病的患者,可进行多学科会诊,在专业药师的参与下制定个体化方案。本指南共形成23条推荐意见,为ATB-DILI的规范诊治提供了临Drug-induced liver injury (DILI) is one of the most common adverse reactions of anti-tuberculosis treatment. To improve the diagnosis and management of anti-tuberculosis drug-induced liver injury (ATB-DILI) for clinicians and tuberculosis control workers, the Chinese Medical Association Tuberculosis Branch has developed guidelines for the diagnosis and treatment of ATB-DILI. These guidelines summarized recent research progress in relevant fields and provide detailed explanations, recommendations, and quality assessments related to ATB-DILI, covering aspects such as definition, risk factors, mechanisms, pathological manifestations, clinical classification, diagnosis, and management. The key recommendations are as follows. Recommendation 1: Risk factors: NAT2 slow acetylation genotype, GSTM1 gene variation, advanced age, hepatitis virus infection or concurrent acute/chronic liver disease, HIV infection, malnutrition, and alcohol (ethanol) intake are risk factors for ATB-DILI (2, B). Recommendation 2: R-value calculation: Calculate the R-value for suspected ATB-DILI patients at different time points during the course of the disease. ALT and ALP values should be obtained on the same day, with a maximum interval of no more than 48 hours. This helps to accurately determine the clinical type and prognosis of DILI (2, C). Recommendation 3: Comprehensive medical history collection: Collect information on past medication history, clinical features, dynamic changes in liver biochemical markers, drug rechallenge reactions, comorbidities, and underlying liver diseases (4, B). Recommendation 4: Liver biochemical tests: Include at least ALT, AST, ALP, GGT, TBil, DBil, and albumin. If necessary, measure prothrombin time or international normalized ratio (INR) (3, B). Recommendation 5: Abdominal imaging: Routine abdominal imaging should be performed for suspected ATB-DILI patients (3, B). Recommendation 6: Liver histopathological examination: Histology of liver biopsies aids in the diagnosis and differential diagnosis of DILI (4,

关 键 词：药物性肝损伤 中华医学会 保肝药物 临床证据 结核病学 抗结核药 利奈唑胺 临床医师 

分 类 号：R978.3[医药卫生—药品]