探讨长期核苷(酸)类药物治疗慢性乙型肝炎患者停药后复发的影响因素

Factors associated with relapse after discontinuation of long-term nucleos(t)ide analogue therapy in patients with chronic hepatitis B

核苷(酸)类药物[Nucleos(t)ide-analogues,NAs]在临床上广泛用于抗乙型肝炎病毒(hepatitis B virus,HBV)治疗,然而其疗程长,难以达到理想的治疗终点停药。近年来,NAs治疗何时能够停药以及何种指标能够较为准确预测停药后应答,备受临床关注。本文从病毒学和宿主免疫学两个方面,概述了关于影响停止NAs治疗后复发的主要因素:(1)血清表面抗原(HBsAg)、核心相关抗原(HBcrAg)和血清HBV RNA这三种病毒学因素在NAs抗病毒治疗终点的研究中具有重要价值;(2)宿主免疫学因素包括细胞因子水平、天然免疫应答以及适应性免疫应答,其中NK细胞和HBV特异性T细胞与NAs停药后细胞宿主免疫应答密切相关;(3)病毒因素以及宿主因素之间的相互作用决定了HBV感染的临床结局。

Nucleos(t)ide-analogues(NAs)is widely applied to the antiviral therapy of hepatitis B virus(HBV)clinically.However,few patients treated with NAs could reach HBsAg clearance,considering the ideal end-point of treatment.Over the past decades,researchers have increasingly focused on optimal stopping strategies,mainly in which indicators could effectively predict clinical outcomes and during which optimal time point to perform.The report summarizes the crucial factors causing the relapse after the NAs treatment is stopped based on virology and host immunology:①Serum HBsAg,HBcrAg,and HBV RNA play crucial roles in determining end-point of NAs’antiviral therapy.②Immunological factors including levels of cytokines,natural immune responses and adaptive immune responses.In addition,NK cell and HBV-specific T cell are closely associated with host immune response.③The interaction between virological and immunological factors induce the clinical outcomes.