恩替卡韦经治慢性乙肝患者低病毒血症的临床研究进展

Research progress of clinical research on low-level viremia in chronic hepatitis B patients receiving entecavir

目前临床上广泛使用恩替卡韦、富马酸替诺福韦酯等核苷(酸)类似物作为一线抗乙肝病毒药,部分患者经此类药物治疗后,其血清HBV DNA虽然降低到2000 IU/mL以下,但仍持续或间歇性地高于检测下限,即处于低病毒血症(low-level viremia,LLV)状态。持续存在的LLV会导致慢性乙肝患者出现耐药风险增加、病毒学突破、促进肝纤维化、肝硬化进展、肝癌风险增加、影响生存率等一系列临床危害。本文重点综述恩替卡韦治疗下LLV的相关临床研究,总结了LLV的规范定义和诊断标准,阐述恩替卡韦相关LLV的临床危害和管理策略,并讨论LLV的发生机制,为此类患者的治疗和管理提供参考。

At present,nucleos(t)ide analogues(NAs)such as entecavir and tenofovir disoproxil fumarate are widely used as first-line anti-hepatitis B virus drugs clinically.After treatment with these drugs,some patients can realize decreased serum hepatitis B virus(HBV)DNA to below 2000 IU/mL.However,these patients may experience persistent or intermittent episodes of detectable HBV DNA higher than the lower limit of detection,which is defined as low-level viremia(LLV).Persistent LLV will lead to a series of clinical hazards in patients with chronic hepatitis B,such as increased risk of drug resistance,virological breakthrough,promotion of liver fibrosis,progression of liver cirrhosis,increased risk of liver cancer,and adverse impact on the survival rate.The present study reviewed the relevant clinical studies of LLV in entecavir-treated individuals,summarized the normative definition and diagnostic criteria of LLV,expounded the clinical hazards and the management strategies after the occurrence of LLV during treatment with entecavir,and discussed the pathogenesis of LLV.Findings in our study are expected to provide reference for the treatment and management of such patients.