治愈乙型肝炎病毒感染：涉及病毒抑制和免疫调节和长期结

StephenW

J Infect Dis. 2017 Nov 16;216(suppl_8):S771-S777. doi: 10.1093/infdis/jix355.
Toward a Cure for Hepatitis B Virus Infection: Combination Therapy Involving Viral Suppression and Immune Modulation and Long-term Outcome.Wu D1, Ning Q1.
Author information
1Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

AbstractChronic hepatitis B virus (HBV) infection remains a major global health burden. Currently, the approved therapeutic regimens include nucleos(t)ide analogues (NAs) and either interferon or pegylated interferon. NA therapy is generally safe and well tolerated, but the rate of posttreatment virologic relapse is high, making NA treatment a lifetime commitment. The benefits of pegylated interferon treatment include a finite duration, more-durable response and absence of viral resistance. However, sustained response to interferon alone is achieved only in a minority of patients, and side effects are common, which limit its clinical use. Given that HBV covalently closed circular DNA and the integrated HBV genome persist stably in the nuclei of infected hepatocytes, elimination (complete cure) of HBV is rarely achieved. After completion of treatment, sustained HBV surface antigen loss, with or without seroconversion to HBV surface antibody positivity (ie, functional cure), is therefore recommended as the ideal end point for anti-HBV treatment, despite the lack of complete eradication of HBV. Theoretically, combination of antiviral agents with differential mechanisms of actions on HBV, including viral suppression combined with immune modulation (as occurs during treatment with NA plus pegylated interferon), is an encouraging strategy to treat chronic hepatitis B. Recent studies have confirmed certain virological and serological advantages of simultaneous administration of NA and pegylated interferon (de novo combination therapy) or addition of pegylated interferon to ongoing NA therapy (sequential combination therapy) over monotherapy. Few data exist, however, on the long-term outcomes of patients receiving combination therapy. This review summarizes current combination therapy developed to cure chronic HBV infection.

© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

KEYWORDS: CHB; HBV; NA; combination therapy; functional cure; pegylated interferon

PMID:29156046DOI:10.1093/infdis/jix355

StephenW

J传染病2017年11月16日; 216（suppl_8）：S771-S777。 doi：10.1093 / infdis / jix355。
治愈乙型肝炎病毒感染：涉及病毒抑制和免疫调节和长期结果的联合治疗。
吴D1，宁Q1。
作者信息

1
    华中科技大学同济医学院附属同济医院传染病研究所，武汉。

抽象

慢性乙型肝炎病毒（HBV）感染仍然是全球主要的健康负担。目前，批准的治疗方案包括核苷（酸）类似物（NAs）以及干扰素或聚乙二醇化干扰素。 NA治疗一般安全且耐受性良好，但治疗后病毒复发率高，使NA治疗成为终生承诺。聚乙二醇干扰素治疗的好处包括有限的持续时间，更持久的反应和没有病毒抗性。然而，只有少数患者对干扰素单独持续应答，且副作用普遍，限制了其临床应用。由于HBV共价闭合的环状DNA和整合的HBV基因组在被感染的肝细胞的细胞核中稳定存在，很难达到消除（完全治愈）HBV的目的。在完成治疗后，尽管没有完全根除HBV，但推荐将持续的HBV表面抗原丢失，伴或不伴有HBV表面抗体阳性（即功能治愈）的血清转换，作为抗HBV治疗的理想终点。理论上，抗病毒药物与HBV作用的不同机制（包括病毒抑制与免疫调节相结合）（如在NA加聚乙二醇化干扰素治疗期间发生的）的组合是治疗慢性乙型肝炎的令人鼓舞的策略。最近的研究已经证实某些病毒学和同时施用NA和聚乙二醇化干扰素（从头组合疗法）或聚乙二醇化干扰素与正在进行的NA疗法（顺序组合疗法）相比单独疗法的加入的血清学优势。然而，关于接受联合治疗的患者的长期结果，很少有数据存在。本综述总结了目前用于治疗慢性HBV感染的联合治疗。

©作者2017.牛津大学出版社出版的美国传染病协会。版权所有。对于权限，电子邮件：[email protected]。
关键词：

CHB; HBV; NA;联合治疗;功能治愈;聚乙二醇干扰素

结论：
    29156046
DOI：
    10.1093 / infdis / jix355

antiHBVren

理论上，抗病毒药物与HBV作用的不同机制（包括病毒抑制与免疫调节相结合）（如在NA加聚乙二醇化干扰素治疗期间发生的）的组合是治疗慢性乙型肝炎的令人鼓舞的策略。最近的研究已经证实某些病毒学和同时施用NA和聚乙二醇化干扰素（从头组合疗法）或聚乙二醇化干扰素与正在进行的NA疗法（顺序组合疗法）相比单独疗法的加入的血清学优势。

——连续3个文章关于NAs与干扰素的联合或贯序治疗，看来这里可以结合出新的治疗方法，对于国人大多数为B2 基因型的HBV来说，有更好的现实意义；

TRUMPHILARY

核苷和干扰素联合治愈率有多高？
副作用能承受吗？