[129例丙硫异烟胺和对氨基水杨酸所致肝毒性的临床分析]

Ge Qi-ping, Wang Qing-feng, Duan Hong-fei, Wang Jun, Chu Nai-hui

Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China.

Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University & Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing 101149, China. Email:

Zhonghua Jie He He Hu Xi Za Zhi. 2013 Oct;36(10):737-40.

OBJECTIVE

To investigate drug-induced liver injury (DILI) in tuberculosis (TB) patients treated with protionamide (Pto) and (or) para-aminosalicylic acid (PAS), and therefore to provide data for using second-line anti-tuberculosis drugs and risk prediction of liver damage.

METHODS

A retrospective analysis was performed for TB patients treated with regimens containing Pto and (or) PAS in Beijing Chest Hospital during Jan. 2008 to Jan. 2013. Cases with DILI were identified, and associated factors including patients' age and gender, time of onset, severity, clinical manifestations and prognosis of DILI were analyzed. The 2 groups were compared with χ(2) test. P < 0.05 was considered to be significant.

RESULTS

A total of 1714 cases were admitted, among whom 226 experienced liver damage during treatment, of which 97 cases were excluded because of underlying alcoholic liver disease, viral hepatitis B and C. Finally, 129 cases were diagnosed as having DILI, resulting in an overall incidence of 7.5% (129/1714), being 9.2% (59/641) in females, and 6.5% (70/1073) in males (χ(2) = 4.143, P < 0.05). DILI in most patients occurred between 1 week to 2 months, with 30.2% (39/129) within 2-4 weeks. 47.3% (61/129) of the patients showed no obvious clinical symptoms of hepatotoxicity. Among different regimens, combination of Pto, PAS and PZA resulted in the highest rate of DILI (20.7%, 19/92), while the rate was 9.8% (8/82) for the combination of Pto and PZA, P < 0.05.

CONCLUSIONS

DILI caused by Pto and PAS should be taken into account, especially in female patients and for multi-drug combination therapy. Liver function should be monitored even in patients without related clinical manifestations for early identification and treatment, and therefore avoiding severe liver damage.

目的

探讨接受丙硫异烟胺（Pto）和（或）对氨基水杨酸（PAS）治疗的肺结核（TB）患者的药物性肝损伤（DILI）情况，为二线抗结核药物的使用及肝损伤风险预测提供数据。

方法

对2008年1月至2013年1月在北京胸科医院接受含Pto和（或）PAS方案治疗的TB患者进行回顾性分析。确定发生DILI的病例，并分析相关因素，包括患者的年龄、性别、发病时间、严重程度、DILI的临床表现及预后。两组间比较采用χ²检验。P<0.05为差异有统计学意义。

结果

共收治1714例患者，其中226例在治疗期间出现肝损伤，因合并酒精性肝病、乙型和丙型病毒性肝炎排除97例。最终确诊DILI 129例，总发生率为7.5%（129/1714），女性发生率为9.2%（59/641），男性发生率为6.5%（70/1073）（χ²=4.143，P<0.05）。多数患者DILI发生在1周~~2个月，2~~4周内发生率为30.2%（39/129）。47.3%（61/129）的患者无明显肝毒性临床症状。不同治疗方案中，Pto、PAS和吡嗪酰胺（PZA）联合应用导致DILI发生率最高（20.7%，19/92），而Pto与PZA联合应用时发生率为9.8%（8/82），P<0.05。