乙型肝炎管理新范式：只有钻石是永恒

StephenW

Br Med Bull. 2015 Sep 15. pii: ldv039. [Epub ahead of print]
New paradigms in hepatitis B management: only diamonds are forever.Coffin CS1, Lee SS2.
Author information

• 1Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada [email protected].
• 2Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
  

AbstractINTRODUCTION: The hepatitis B virus (HBV) causes chronic hepatitis B (CHB) in ∼350 million people worldwide who have an increased risk of end-stage liver disease and/or hepatocellular carcinoma.
SOURCES OF DATA: Several peer-reviewed papers featuring new approaches to anti-HBV management. Additionally, we also reviewed recent abstract presentations at international congresses.
AREAS OF AGREEMENT: There has been great progress in CHB therapy with the development of standard and pegylated interferon (i.e. PEG-IFN) as well as nucleos/tide analogs (NAs). IFN has both antiviral and immunomodulatory effects and through immune-mediated destruction of infected hepatocytes offers the possibility of finite therapy. However, this 'killing for a cure' antiviral strategy may not be tolerated in many, especially in cirrhotic patients. NAs inhibit viral reverse transcriptase, have few side effects and prevent liver disease progression, but cannot offer a cure as they have little effect on the resilient HBV covalently closed circular DNA (cccDNA) intermediate. Moreover, NAs such as tenofovir and entecavir offer a high genetic barrier to resistance, but are expensive and not readily available in many global regions.
GROWING POINTS: Despite significant treatment advances, there is increased recognition of the need for improved anti-HBV treatments, and new virologic tests for monitoring treatment response.
AREAS OF CONTROVERSY: The role of quantitative hepatitis B surface antigen, intrahepatic cccDNA levels and viral genotype in selecting treatment candidates and refining NA stopping rules.
AREAS TIMELY FOR DEVELOPING NEW RESEARCH: Potential new therapies include viral entry inhibitors, RNA interference technologies (i.e. RNAi) and small molecules that modulate cccDNA transcription, as well as novel immunomodulatory therapies to boost HBV-specific T cell responses. The ultimate goal of new tests and anti-HBV therapies is to reduce the burden and expense of life-long CHB treatment, as 'only diamonds are forever'.
© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

StephenW

BR医学公牛。 2015年九月15 PII：ldv039。 [打印EPUB提前]
乙型肝炎管理新范式：只有钻石是永恒。
棺材CS1，李SS2。
作者信息

    1Liver单位，胃肠病学和肝病科，医学系，医学系，卡尔加里，卡尔加里，加拿大[email protected]大学。
    2Liver单位，胃肠病学和肝病科，医学系，医学系，卡尔加里，卡尔加里大学，加拿大。

抽象的
简介：

乙型肝炎病毒（HBV）引起慢性乙型肝炎（CHB）在全世界~350万人谁具有终末期肝病和/或肝细胞癌的风险增加。
数据来源：

一些同行评审的论文采用新的方法来抗HBV管理。此外，我们还审查了国际大会最近抽象的演讲。
协议领域：

已经有慢性乙型肝炎治疗的标准和聚乙二醇干扰素的发展（即PEG-IFN）及核苷/潮类似物（NAS）很大的进步。干扰素具有抗病毒都和免疫调节作用，并通过感染的肝细胞的免疫介导的破坏，提供有限的治疗的可能性。然而，这种“杀人的治疗”抗病毒策略，可能不会容忍很多，尤其是肝硬化患者。港定居抑制病毒逆转录酶，具有副作用少，并防止肝脏疾病进展，但不能提供治疗，因为它们对弹性HBV共价闭合环状DNA（cccDNA的）中间的影响不大。此外，新来港，如替诺福韦和恩替卡韦提供高耐药基因屏障，但价格昂贵，而不是在全球许多地区一应俱全。
生长点：

尽管显著治疗进展，人们越来越认识到需要改善的抗乙肝病毒治疗和新病毒学测试监测治疗的反应。
争议领域：

定量乙肝表面抗原，肝内的cccDNA水平和病毒基因型在选择治疗的候选人和精炼NA停止规则的作用。
地区及时开发新的研究：

潜在的新的治疗方法包括病毒进入抑制剂，RNA干扰技术（即RNAi）的和小分子调节cccDNA的转录，以及新颖的免疫调节治疗，以提高HBV特异性T细胞应答。新的测试和抗乙肝病毒治疗的最终目标是减少终身治疗慢性乙型肝炎的负担和费用，因为“只有钻石是永恒的”。

©该作者2015年出版由牛津大学出版社。版权所有。对于权限，请电邮：[email protected]。