卡介苗膀胱灌注相关肉芽肿性肝炎的临床特点分析  

Analysis on clinical features of granulomatous hepatitis induced by intravesical instillation with Bacillus Calmette-Guérin vaccine

作　　者：倪倍倍[1] 赵俊[1] 曹战起 郭切[1] 徐文[1] 冷萍[1] Ni Beibei;Zhao Jun;Cao Zhanqi;Guo Qie;Xu Wen;Leng Ping(Department of Pharmacy,the Affiliated Hospital of Qingdao University,Shandong Province,Qingdao 266071,China)

机构地区：[1]青岛大学附属医院药学部,青岛266071

出　　处：《药物不良反应杂志》2022年第5期252-257,共6页Adverse Drug Reactions Journal

基　　金：山东省自然科学基金(ZR2020MH418)。

摘　　要：目的了解卡介苗膀胱灌注(BCG灌注)相关肉芽肿性肝炎(GH)的临床特点。方法检索PubMed和Elsevier数据库(截至2021年12月),收集报道BCG灌注相关GH且GH经肝活检证实的病例报告类文献。记录患者基本情况,BCG灌注情况(剂量、次数、导管插入有无异常等),GH发生情况(发生时间、主要症状、相关实验室检查和肝活检结果),其他不良反应发生情况,以及干预措施和转归情况,进行描述性统计分析。结果纳入分析的患者共23例,均为男性;年龄34~80岁,中位年龄66岁;膀胱癌22例,肾盂肾癌1例;19例有发生GH前灌注次数记录,灌注1次者2例,最多者为16次;最近一次灌注导管插入时出现异常者10例,其中血尿7例,疼痛2例,1例插管困难。GH发生在最近一次BCG灌注后3 h~440 d(≤7 d者18例,10、14、21、180、440 d者各1例),中位时间为3 d。23例患者中,出现发热症状者21例,黄疸12例,肝肿大9例,乏力7例,厌食5例,体重减轻2例,盗汗1例;单独表现为GH者12例,伴发其他不良反应者11例。22例患者出现肝功能异常,主要表现为碱性磷酸酶升高和天冬氨酸转氨酶升高(各17例)。20例患者记录了牛型结核分枝杆菌鉴定/培养情况,7例阳性。肝活检结果显示,23例患者中非干酪性上皮样肉芽肿者10例,非干酪性肉芽肿7例,上皮样肉芽肿4例,仅记录肝肉芽肿2例。停止BCG灌注治疗并给予抗结核药物和/或糖皮质激素治疗后,22例患者好转,1例死于牛型结核分枝杆菌败血症和多器官衰竭。结论GH多发生于BCG灌注后1周内,主要临床表现为发热、黄疸、肝肿大和肝功能异常,可伴发其他BCG灌注相关不良反应。肝活检可明确诊断。采用抗结核药物与糖皮质激素联合治疗,多数预后较好,但严重者可致死。Objective To understand the clinical features of granulomatous hepatitis(GH)induced by intravesical instillation with Bacille Calmette-Guérin vaccine(BCG).Methods Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021.The following information of patients including general information,intravesical BCG situations(dose,times of instillation,traumatic catheterization occurrence),GH occurrence(onset time,clinical manifestations,laboratory tests and liver biopsy results),other adverse reactions,treatments,and outcomes were extracted and analyzed descriptively.Results A total of 23 patients,who were all male,were entered in the analysis,aged from 34 to 80 years with a median age of 66 years.The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient.The times of instillation until GH occurred were recorded in 19 patients.Of them,2 patients had instillation once and the time was 16 at most.Ten patients had traumatic catheterization during the last instillation,including hematuria in 7 patients,pain in 2 patients,and difficulty in urethral intubation in 1 patient.Time from the last instillation to the onset of GH was from 3 h to 440 days(≤7 days in 18 patients,10,14,21,180,and 440 days in 1 patient respectively)with a median time of 3 days.Among the 23 patients,21 had fever,12 had jaundice,9 had hepatomegaly,7 had fatigue,5 had anorexia,2 had weight loss,and 1 had night sweats;12 manifested as GH alone and 11 had concomitant adverse reactions.Abnormal liver function appeared in 22 patients,mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase(each in 17 patients).Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive.Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients,noncaseating granuloma in 7 patients,epithelioid granuloma in 4 patients,and hepatic granuloma without de

关 键 词：投药 膀胱内 卡介苗 肉芽肿病 慢性 肝炎 

分 类 号：R575.1[医药卫生—消化系统]