合并慢性乙型肝炎病毒感染的炎性关节病患者使用肿瘤坏死因子-α拮抗剂的肝脏安全性前瞻陛观察  

Liver safety of tumor necrosis factor-or antagonists in inflammatory arthropathy patients with concurrent chronic hepatitis B infection： a prospective observation

作　　者：莫颖倩[1] 戴冽[1] 郑东辉[1] 邹婵娟[1] 马剑达[1] 李艳华[1] 朱浪静[1] 张白玉[1] 

机构地区：[1]中山大学孙逸仙纪念医院风湿免疫科,广州510120

出　　处：《中华风湿病学杂志》2012年第5期317-321,共5页Chinese Journal of Rheumatology

基　　金：基金项目：中国医疗手牵手工程委员会北京医学奖励基金会课题（FSMYYSZS-001）

摘　　要：目的探讨肿瘤坏死因子（TNF）-a拮抗剂对炎性关节病患者乙型肝炎病毒（HBV）再激活及肝功能的影响。方法活动期类风湿关节炎（RA）及强直性脊柱炎（AS）患者根据HBV血清学指标分组，动态随访TNF-a拮抗剂治疗后HBV再激活及肝功能情况。多组间连续变量比较采用Kruskal—Wallis非参数检验，分类变量比较采用矿检验或Fisher精确概率法。结果50例患者完成随访，随访时间3～23个月。治疗后转氨酶水平慢性HBV感染组患者[11例，天冬氨酸转氨酶（AST）：（36±18）U／L，丙氨酸转氨酶（ALT）：（44±46）U／L]显著高于既往HBV感染组[16例，AST：（22±6）U／L，ALT：（17±9）U／L]和无HBV感染组[23例，AST：（19±6）U／L，ALT：（15±9）U／L]（AST：x2=11．161，P〈0．01；ALT：x2=8．038，P〈0．01）。1例基线HBV-DNA升高的AS患者治疗前加用拉米夫定，4个月后HBV—DNA降至接近正常；余10例基线HBV—DNA阴性的慢性HBV感染患者中，1例治疗后发生HBV再激活伴转氨酶升高，1例仅有转氨酶升高而HBV—DNA持续阴性，且停药后转氨酶自行回复正常，考虑为药物的肝损害。既往HBV感染组及无感染组患者治疗后未出现乙型肝炎表面抗原（HBsAg）转阳。结论炎性关节病患者使用TNF-a拮抗剂前须筛查HBV感染及肝功能情况，治疗期间需密切监测肝功能及HBV再激活情况，基线HBV-DNA阳性（尤其〉10^5 copies／ml）或经济能力允许的合并慢性HBV感染的患者应在治疗前开始预防性抗病毒治疗。Objective To investigate the effect of tumor necrosis factor （TNF）-a antagonists on liver function and reactivation of hepatitis B virus （HBV） in patients with inflammatory arthropathy with concurrent chronic HBV infection. Methods Patients with active rheumatoid arthritis （RA） and ankylosing spondylitis （AS） who were grouped according to serum HBV biomarkers were treated with TNF-a antagonist. The liver function and reactivation of HBV were monitored before and after anti-TNF-a therapy. Kruskal-Wallis one-way analysis of variance on ranks of continuous variables andx2 test or Fisher＇s exact test for categorical variables among 3 or more groups. Results Fifty patients were enrolled with 3 to 23 months of follow-up visit. The level of transaminases in chronic HBV infection group [n=ll, AST （36±18） U/L, ALT （44±46） U/L] were significantly higher than that in past HBV exposure group [n=16, AST （22±6） U/L, ALT （17±9） U/L] or free of HBV infection group [n=23, AST （19±6） U/L, ALT （15±9） U/L]（AST： x2=11.161, P〈0.01, ALT： X2=8.038, P〈0.01）. One patient with elevated baseline HBV-DNA load was treated concomitantly with lamivudine and anti-TNF-a therapy, and the HBV-DNA load reduced about to normal 4 months later. Among the other 10 patients with normal baseline HBV-DNA load in chronic HBV infection group, one patient showed reactivation of HBV with elevated transaminases after anti-TNF-a therapy; another patient had only elevated transaminases without reactivation of HBV, and the transaminases returned to normal after withdrawal of anti TNF-a therapy, which suggested drug-induced liver injury. All patients in both past HBV exposure group and free of HBV infection group remained HBsAg negative after the therapy. Conclusion Patients with inflammatory arthropathy should be screened for HBV infection and check liver function before anti-TNF-a therapy, and carefully monitor the reactivation of HBV and liver function during treatment. Patients with concurrent chronic

关 键 词：肿瘤坏死因子A 关节炎 类风湿 脊柱炎 强直性 肝炎 乙型 前瞻性研究 

分 类 号：R593[医药卫生—内科学] R51[医药卫生—临床医学]