含丙硫异烟胺和对氨基水杨酸治疗方案发生药物性肝损伤129例临床分析

Clinical analysis of protionamide and para-aminosalicylic acid induced hepatotoxicity in 129 cases

目的 了解含丙硫异烟胺（Pto）和（或）对氨基水杨酸（PAS）的抗结核治疗方案发生药物性肝损伤（DILI）情况,为及时合理治疗DILI提供依据.方法 回顾性分析2008年1月至2013年1月北京胸科医院应用含Pto和（或）PAS方案治疗的结核病患者发生DILI情况,对DILI的发生时间、年龄、性别、严重程度、临床表现及转归等方面进行分析.两组间比较采用x2检验.结果 含Pto 和（或）PAS方案的患者共1714例,治疗中发生DILI者226例,排除病毒性肝炎、酒精性肝病及不能确定抗结核药物所致DILI者97例,抗结核药物所致DILI共129例,总发生率为7.5％ （129/1714）,女性DILI发生率（9.2％,59/641）高于男性（6.5％,70/1073）,差异有统计学意义（x2=4.143,P＜0.05）.DILI多发生于用药后1～2个月,以2～4周多见（30.2％,39/129）,47.3％ （61/129）的患者发生DILI时无明显临床症状.在不同抗结核药物组合方案中,Pto＋ PAS＋吡嗪酰胺方案的DILI发生率最高（20.7％,19/92）,且显著高于Pto＋吡嗪酰胺方案（9.8％,8/82）,差异有统计学意义（x2=3.927,P＜0.05）.结论 应用含Pto和（或）PAS等二线抗结核药物时应警惕DILI的发生,尤其是女性及Pto＋ PAS＋吡嗪酰胺联合应用患者,在抗结核治疗中无明显临床表现时也应定期复查肝功能,做到早发现、早治疗DILI,避免严重DILI的发生.

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 x2 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 （x2 =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.