卡介苗膀胱灌注相关肝炎临床病理特征分析

Clinicopathological features of granulomatous hepatitis induced by Bacillus Calmette-Guerin(BCG)bladder instillation:a case series and literature review

目的 阐明卡介苗膀胱灌注相关肝炎的临床病理特征。方法 2023年北京友谊医院诊治的卡介苗膀胱灌注相关肝损伤患者2例,通过文献检索卡介苗膀胱灌注相关肝损伤21例。总结患者性别、年龄、卡介苗膀胱灌注次数、肝脏生化结果、肝脏病理活检、结核杆菌检测结果、治疗方案、预后等信息。结果 本中心共诊治2例、文献共报道21例资料较为齐全的卡介苗膀胱灌注相关肝损伤。23例患者均为男性,年龄66(34~88)岁,接受卡介苗膀胱灌注次数为6(1~17)次。主要表现为ALP和(或)GGT明显升高,伴或不伴ALT和AST升高,52.2%(12/23)患者血清TBil升高。结核菌检测阳性6例,阴性14例,检测结果不详3例。共20例接受肝穿刺活检,其中19例呈肉芽肿性肝炎,1例呈汇管区扩大及炎症细胞浸润,未见肉芽肿形成。7例接受抗结核治疗,14例接受抗结核+激素治疗,2例只接受激素治疗。87.0%(20/23)患者痊愈,2例患者好转后没有继续随访,死亡2例。结论 卡介苗膀胱灌注相关肝炎表现为ALP和(或)GGT明显升高,约半数患者可出现黄疸,绝大部分呈肉芽肿性肝炎,少数患者可找到结核分枝杆菌。部分患者经过抗结核治疗痊愈,大部分患者抗结核联合激素治疗、部分患者只接受激素治疗后痊愈,提示免疫反应参与了疾病的发生发展。

Objective To elucidate the clinicopathological characteristics of hepatitis associated with Bacillus Calmette-Guerin(BCG)bladder instillation.Methods We summarized and documented cases of hepatitis associated with BCG bladder instillation treated at Beijing Friendship Hospital.A systematic review of previously reported cases were conducted.Data were collected and analyzed on variables including gender,age,frequency of BCG bladder instillations,liver biochemical results,liver histopathology,Mycobacterium tuberculosis testing,treatment regimens,and patient outcomes.Results A total of 23 patients,including 2 cases from our center and 21 cases from the literature,were re-evaluated.All patients were male,with a median age of 66 years at onset(range 34-88)and had received a median of 6 BCG bladder instillations(range 1-17).All patients exhibited a significant increase in alkaline phosphatase(ALP)and/or gamma-glutamyl transferase(GGT),with most also demonstrating varying degrees of elevated alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Additionally,52.2%(12/23)of the patients had elevated serum total bilirubin(TB).Among the cases,6 tested positive for Mycobacterium tuberculosis,14 tested negative and 3 had unclear results.Liver biopsies were performed in 20 cases,revealing granulomatous hepatitis in 19 cases,while 1 case showed expansion and infiltration of inflammatory cells in the portal area without granuloma formation.Seven patients received anti-tuberculosis treatment,14 were treated with a combination of anti-tuberculosis and glucocorticoid therapy,and 2 received glucocorticoids alone.Outcomes were favorable in 87%(20/23)of cases,with recovery noted in 20 patients;2 cases improved but were lost to follow-up,and 1patient died.Conclusion Hepatitis resulting from intravesical BCG is rare and typically manifests with elevated ALP and/or GGT levels,often accompanied by jaundice.Most cases present as granulomatous hepatitis,with only a few miniority testing positive for Mycobacterium tuberculosis.While some patients recovered with anti-tuberculosis treatment alone,the majority required a combination of anti-tuberculosis therapy and glucocorticoid,or achieved recovery with glucocorticoids alone,suggesting a significant role of the immune response in the pathogenesis of the disease.