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免疫抑制治疗致自身免疫性疾病患者乙型肝炎病毒再激活:乙型肝炎表面抗原阴性病例的风险分析。

Hepatitis B virus reactivation by immunosuppressive therapy in patients with autoimmune diseases: risk analysis in Hepatitis B surface antigen-negative cases.

机构信息

Department of Medicine II, Hokkaido University Graduate School of Medicine, N15W7 Kita-Ku, Sapporo 060-8638, Japan.

出版信息

J Rheumatol. 2011 Oct;38(10):2209-14. doi: 10.3899/jrheum.110289. Epub 2011 Aug 15.

Abstract

OBJECTIVE

To evaluate the risk of reactivation of resolved hepatitis B virus (HBV) by immunosuppressive therapy in patients with autoimmune diseases.

METHODS

Thirty-five patients with autoimmune diseases were included in our study; all were hepatitis B surface antigen (HBsAg)-negative and antibody against hepatitis B core antigen-positive. They were followed for 8-124 weeks and clinical outcomes were analyzed, including serum levels of HBV-DNA and aminotransferase every 4 weeks during their immunosuppressive therapy for underlying autoimmune diseases. If HBV-DNA was detected during the immunosuppressive therapy, HBsAg, antibody against HBsAg (anti-HBs), hepatitis B e antigen (HBeAg), and antibody against HBeAg were also monitored every 4 weeks.

RESULTS

HBV-DNA was detected in 6 out of 35 patients. Anti-HBs titer was significantly lower in the patients in whom HBV-DNA was detected compared with the others at baseline: 2.83 (range 0.24-168.50) mIU/ml vs 99.94 (range 0.00-5342.98) mIU/ml, respectively (p = 0.036). Outcomes of the 6 patients with HBV reactivation were as follows: HBV-DNA turned negative in 2 patients without nucleic acid analog (NAA) and 1 with NAA; 2 died due to bacterial sepsis; and 1 died due to autoimmune hemolytic anemia. Significant elevation of aminotransferase was found in only 1 patient, but HBsAg converted to positive in 2 patients and HBeAg converted to positive in 1 patient.

CONCLUSION

Reactivation of resolved HBV can occur during standard immunosuppressive therapy for autoimmune diseases. The low titer of baseline anti-HBs may carry its risk.

摘要

目的

评估自身免疫性疾病患者接受免疫抑制治疗后已缓解的乙型肝炎病毒(HBV)再激活的风险。

方法

本研究纳入了 35 例自身免疫性疾病患者;所有患者乙型肝炎表面抗原(HBsAg)阴性,乙型肝炎核心抗原抗体阳性。对他们进行了 8-124 周的随访,并分析了临床结果,包括在接受基础自身免疫性疾病的免疫抑制治疗期间每 4 周检测一次血清 HBV-DNA 和转氨酶水平。如果在免疫抑制治疗期间检测到 HBV-DNA,则每 4 周监测 HBsAg、HBsAg 抗体(抗-HBs)、乙型肝炎 e 抗原(HBeAg)和抗-HBe 抗体。

结果

35 例患者中有 6 例检测到 HBV-DNA。与其他患者相比,HBV-DNA 检测阳性的患者基线时的抗-HBs 滴度明显较低:分别为 2.83(范围 0.24-168.50)mIU/ml 和 99.94(范围 0.00-5342.98)mIU/ml(p=0.036)。6 例 HBV 再激活患者的结局如下:2 例未使用核酸类似物(NAA)和 1 例使用 NAA 的患者 HBV-DNA 转为阴性;2 例因细菌败血症死亡;1 例因自身免疫性溶血性贫血死亡。仅 1 例患者出现明显的转氨酶升高,但有 2 例患者 HBsAg 转为阳性,1 例患者 HBeAg 转为阳性。

结论

在治疗自身免疫性疾病的标准免疫抑制治疗期间,已缓解的 HBV 可能会再激活。基线时低滴度的抗-HBs 可能存在风险。

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