核苷类抗病毒药预防治疗糖皮质激素诱导的HBV再激活临床回顾性分析

Retrospective analysis of the effect of nucleoside analogues on HBV reactivation due to glucocorticoid therapy

目的回顾性分析因免疫性基础疾病等使用糖皮质激素的慢性HBV感染者,应用核苷类药物预防治疗HBV再激活及免疫性疾病活动的临床效果。方法随机选取131例HBV感染并因免疫性疾病应用糖皮质激素治疗的患者,分为3组:A组41例,血清ALT正常,HBV DNA载量≤1×103copies/ml;B组67例,ALT<2倍正常值上限(upper limits of normal,ULN),1×103copies/ml<HBV DNA载量<1×104copies/ml;C组23例,ALT≥2×ULN,HBV DNA载量≥1×104copies/ml,应用拉米夫定、恩替卡韦或拉米夫定+阿德福韦酯治疗,每3个月随访HBV DNA载量和ALT水平。结果口服核苷类药物可明显抑制病毒复制,有利于控制免疫性疾病活动。如不给予核苷类药物治疗,当HBV DNA载量>1×103copies/ml时HBV DNA复制和免疫性疾病活动风险更高。但无论病毒载量高低,采用单药拉米夫定/恩替卡韦,或拉米夫定+阿德福韦酯均出现良好应答。对拉米夫定单药或加用阿德福韦酯应答不良者,恩替卡韦治疗仍可获得理想应答。结论因免疫性疾病采用糖皮质激素治疗的患者,无论HBV DNA载量是否高于正常值,均应给予核苷类药物治疗,且应尽早使用强效、低耐药的药物。

Objective To retrospectively analyze the therapeutic efficacy of nucleoside analogues on HBV reactivation and activation of underlying immune diseases in chronically HBV-infected patients receiving glucocorticoid therapy due to underlying immune diseases. Methods A total of 131 HBV-infected patients receiving glucocorticoid therapy due to underlying immune diseases were enrolled in the study. They were divided into 3 groups according to the serum levels of HBV DNA and ALT. There were 41 patients in group A with normal serum level of ALT and HBV DNA ≤1×103 copies/ml, 67 patients in group B with ALT less than twice upper limits of normal （ULN） and HBV DNA 〉1 ×103 copies/ml but 〈1 ×104 copies/ml, and 23 patients in group C with ALT no less than twice ULN and HBV DNA ≥1 ×104 copies/ml. Antiviral treatment strategies included lamivudine （LAM） therapy, entecavir （ETV） therapy or LAM＋adefovir dipivoxil （ADV） therapy. The serum levels of HBV DNA and ALT were detected every 3 months. Results Oral administration of nucleoside analogues could inhibit viral replication significantly, and helped control the activation of underlying immune diseases. If nucleoside analogue therapy was not given, the patients with HBV DNA〉1 ×103 copies/ml would be at higher risk for viral replication and the activation of underlying immune diseases. However, regardless of the level of HBV DNA, the patients showed good response to LAM, ETV or LAM＋ADV. Those who didn＆#39;t respond well to LAM or LAM＋ADV might obtain good response to ETV. Conclusions Patients receiving glucocorticoid therapy due to underlying immune diseases, regardless of the level of HBV DNA, should be given nucleoside analogue therapy, and early use of antiviral agents with high effectiveness and low drug resistance is recommended.