再生障碍性贫血合并乙型肝炎病毒感染60例免疫抑制治疗疗效分析

Reactivation of hepatitis B virus infection in aplastic anemia patients treated by immunosuppressive therapy

目的评价再生障碍性贫血(AA)合并乙型肝炎病毒(HBV)感染患者免疫抑制治疗(IST)过程中病毒活化及预防。方法回顾性分析2013年12月至2016年11月就诊于南京医科大学第一附属医院血液科收治的201例重型及非重型再生障碍性贫血(SAA/NSAA)患者接受抗胸腺细胞免疫球蛋白(ATG)联合环孢素A(CsA)或单用CsA行IST时HBV感染情况,评价治疗前后的肝功能、乙肝两对半、HBV-DNA定量和血液学疗效。结果共60例(29.8%)AA患者伴HBV感染(SAA 15例,NSAA 45例),其中HBsAg阳性12例(20.0%);HBsAg阴性48例(80.0%)。所有患者应用IST前肝功能正常、HBV-DNA定量低于检测下限。IST后,5例(8.3%)出现HBV激活,均为HBsAg阳性(含合并HBe抗原阳性1例)且未预防治疗者,抗病毒药物治疗后4例HBV-DNA控制于检测范围内。7例HBsAg阳性使用抗病毒预防未出现病毒复制。抗-HBc抗体阳性者未使用预防性抗病毒治疗,IST后无病毒激活。HBV感染组与无HBV感染组的IST治疗有效率各为43.1%和37.6%(P=0.469);HBV感染组中,使用抗HBV治疗者IST有效率为50.0%,未用者为39.5%(P=0.496)。结论 AA合并HBV感染,若HBsAg阳性者,不预防性抗病毒治疗有病毒激活风险;AA合并HBV感染不影响对IST疗效,抗HBV治疗不影响IST的疗效。

Objective To investigate the risk of hepatitis B virus（HBV） reactivation in patients with aplastic anemia （AA） complicated with HBV infection and its preventive measure during therapy （IST）. Methods The clinical infection data of 201 cases with severe and non-severe aplastic anemia （SAA/NSAA） received cyclosporine （CsA） alone or combined with anti-thymocyte globulin （ATG） in the Department of Hematolog~ the First Affiliated Hospital of Nanjing Medical University from December 2013 to November 2016 were retrospectively analyzed. The clinical effects and laboratory examination index were evaluated. Result A total of 60 cases （29.8%） with AA complicated with HBV infection （SAA 15 cases, NSAA 45 cases）, 12 cases （20%） were HBsAg positive, and 48 cases （80%） with HBc-Ab but HBsAg were negative. Before IST, all patients had normal liver function, and HBV-DNA was lower than the detection limit. After IST, 5 （8.3%） of 12 patients with HBsAg positive （including one with HBeAg） suffered virus reactivation, since without prophylactic antiviral therapy. Quantification of HBV-DNA and the liver fimction returned to normal level in 4 of these 5 patients after antiviral medicine was administered. No virus reactivation happened in the remaining 7 patients received prophylactic antiviral therapy. No virus reactivation happened in other 48 patients with HBc-Ab but negative HBsAg, although no prophylactic antiviral therapy was used. The response rate of IST in HBV infection group and non-HBV infection group was 43.1% and 37.6% （P=0.469） respectively, the response rate of IST about antiviral therapy group were similar with non-antiviral therapy group there was no significant difference （50.0% vs. 39.5%, P=0.496）. Conclusion AA patients with HBV infection, higher risk of virus reactivation was observed in patients with positive HBsAg and non prophylactic antiviral therapy, the HBV infection and anti-HBV therapy had noinfluence on the efficacy of IST.