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抗 HBc 阳性的风湿性疾病患者采用改善病情抗风湿药物治疗的管理 - 2054 例患者的单中心分析。

Management of anti-HBc-positive patients with rheumatic diseases treated with disease-modifying antirheumatic drugs-a single-center analysis of 2054 patients.

机构信息

Division of Rheumatology/Immunology, University Hospital Wuerzburg, Würzburg, Germany.

Institute for Hygiene and Microbiology, University of Wuerzburg, Würzburg, Germany.

出版信息

Clin Rheumatol. 2018 Nov;37(11):2963-2970. doi: 10.1007/s10067-018-4295-8. Epub 2018 Sep 20.

Abstract

Hepatitis B virus (HBV) reactivation is a common complication of immunosuppressive treatment in high prevalence countries. Biological disease-modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than conventional immunosuppressants. The incidence of HBV reactivation during treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains open how to treat and monitor patients at risk during immunosuppressive therapy with bDMARDs. We examined 2054 patients from a German tertiary rheumatology center in order to analyze the prevalence of HBc-antibody-positivity and the incidence of HBV reactivation in German rheumatology patients treated with immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of HBV infection (anti-HBc positive). Only two patients were suffering from chronic infection (HBsAg positive). Three patients were treated pre-emptively with entecavir, and eight patients after HBV DNA reappearance. No liver failure occurred due to HBV reactivation. Compared to anti-HBc-positive patients without reactivation, the reactivation group included more patients exposed to three or more classes of bDMARDs (p = 0.017). The median HBs antibody titer was significantly lower in the reactivation group (15.0 IU/l vs. 293.5 IU/l; p = 0.001). This study shows that bDMARDs and csDMARDs can safely be administered to patients with a history of HBV, provided they are closely monitored. Low titers of anti-HBs antibodies and a history of ≥ 3 classes of immunosuppressants increase the risk of HBV reactivation. These data highlight major differences to high prevalence regions.

摘要

乙型肝炎病毒 (HBV) 再激活是高流行国家免疫抑制治疗的常见并发症。生物疾病修饰抗风湿药物 (bDMARDs) 比传统免疫抑制剂更常引起这种不良事件。在德国,治疗风湿性疾病期间 HBV 再激活的发生率尚不清楚。此外,在使用 bDMARDs 进行免疫抑制治疗时,如何治疗和监测有风险的患者仍存在争议。我们检查了一家德国三级风湿病中心的 2054 名患者,以分析德国风湿病患者在接受免疫抑制剂治疗时 HBV 核心抗体阳性的患病率和 HBV 再激活的发生率。在 2008 年至 2017 年期间,1317 名接受 bDMARDs 治疗和 737 名接受传统合成 DMARD(csDMARDs)治疗的患者中,有 86 名有 HBV 感染史(抗-HBc 阳性)。只有两名患者患有慢性感染(HBsAg 阳性)。三名患者接受恩替卡韦预防性治疗,八名患者在 HBV DNA 再次出现后接受治疗。没有因 HBV 再激活而导致肝衰竭。与未再激活的抗-HBc 阳性患者相比,再激活组中接受三种或更多类 bDMARDs 治疗的患者更多(p = 0.017)。再激活组的 HBs 抗体滴度明显较低(15.0 IU/l 与 293.5 IU/l;p = 0.001)。这项研究表明,在密切监测的情况下,bDMARDs 和 csDMARDs 可以安全地用于有 HBV 病史的患者。低滴度的抗-HBs 抗体和≥3 类免疫抑制剂的病史会增加 HBV 再激活的风险。这些数据突出了与高流行地区的主要差异。

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