结核病治疗期间肝毒性的管理及相关风险因素

Management of and risk factors related to hepatotoxicity during tuberculosis treatment.

作者信息

Babalık Aylin, Arda Hülya, Bakırcı Nadi, Ağca Sinem, Oruç Korkmaz, Kızıltaş Sule, Cetintaş Gülgün, Calışır Haluk C

机构信息

Clinic of Chest Diseeases, Sureyyapasa Chest Diseases and Chest Surgery Training and Research Hospital, Istanbul, Turkey.

出版信息

Tuberk Toraks. 2012;60(2):136-44.

PMID:22779934

Abstract

INTRODUCTION

Hepatotoxicity is one of the most frequent adverse events occurring during tuberculosis treatment that may negatively affect treatment compliance, clinical outcome. This study was designed to evaluate management, risk factors related to hepatotoxicity during tuberculosis treatment.

PATIENTS AND METHODS

Hospitalized patients for tuberculosis treatment at Sureyyapasa Chest Diseases, and Chest Surgery Training and Research Hospital were included, between January 2004 and December 2007. Prevalence of hepatotoxicity, risk factors were evaluated among tuberculosis patients under anti-tuberculosis treatment according to World Health Organization (WHO) guideline. Hepatotoxicity was defined any elevated liver function tests with accompanying symptoms. Age, gender, past history of anti-tuberculosis treatment, extensity of radiological findings, co-morbid disorders and drug resistance were the risk factors evaluated in terms of development and recurrence of hepatotoxicity.

RESULTS

Of 1443 patients (38.37 ± 16.74 years; 64.5% were males), 106 (7.3%) was identified to develop hepatotoxicity on an average of 20 days after beginning treatment and lasting an average of 14 days. Hepatotoxicity for once in 78.3% (n= 83) of patients and more than once in 21.7% (n= 23) patients. All anti-tuberculosis drugs was continued at full dosage after the normalization of liver enzyme in 76.4% (n= 81). In recurrence a step-by-step treatment was re-started by exclusion of responsible drug/s. Treatment was administered without modification of WHO regimes in 79.2%. Pyrazinamide was omitted in 15 cases while rifampicin only in one patient. Triple drug regimen with isoniazid, ethambutol and streptomycin was used in six cases. Quinolon was added to treatment only in one patient. Presence of a co-morbidity was determined to be significant predictor of hepatotoxicity development OR= 3.093 (CI= 1.95-4.89; p= 0.000) past history of anti-tuberculosis treatment was significantly associated with recurrence (p= 0.027). There was no hepatotoxicity dependent mortality.

CONCLUSION

Hepatotoxicity can be successfully management of hepatotoxicity without second line tuberculosis drugs in ongoing treatment regime.

摘要

引言

肝毒性是结核病治疗期间最常见的不良事件之一，可能会对治疗依从性和临床结局产生负面影响。本研究旨在评估结核病治疗期间肝毒性的管理及相关危险因素。

患者与方法

纳入2004年1月至2007年12月期间在苏雷亚帕萨胸科疾病与胸外科培训及研究医院住院接受结核病治疗的患者。根据世界卫生组织（WHO）指南，对接受抗结核治疗的结核病患者中肝毒性的患病率及危险因素进行评估。肝毒性定义为伴有症状的任何肝功能检查指标升高。年龄、性别、既往抗结核治疗史、放射学检查结果的范围、合并症及耐药性是根据肝毒性的发生和复发情况进行评估的危险因素。

结果

1443例患者（年龄38.37±16.74岁；64.5%为男性）中，106例（7.3%）在开始治疗后平均20天被确定发生肝毒性，平均持续14天。78.3%（n = 83）的患者肝毒性发生一次，21.7%（n = 23）的患者发生不止一次。76.4%（n = 81）的患者在肝酶正常化后继续全剂量使用所有抗结核药物。复发时，通过排除相关药物逐步重新开始治疗。79.2%的患者按照WHO方案进行治疗，未作修改。15例患者停用吡嗪酰胺，仅1例患者停用利福平。6例患者使用异烟肼、乙胺丁醇和链霉素的三联药物方案。仅1例患者在治疗中加用喹诺酮类药物。合并症的存在被确定为肝毒性发生的显著预测因素，OR = 3.093（CI = 1.95 - 4.89；p = 0.000），既往抗结核治疗史与复发显著相关（p = 0.027）。未出现与肝毒性相关的死亡。