Locarnini Stephen, Hatzakis Angelos, Heathcote Jenny, Keeffe Emmet B, Liang T Jake, Mutimer David, Pawlotsky Jean-Michel, Zoulim Fabien
Victorian Infectious Diseases Reference Laboratory, North Melbourne, Vic., Australia.
Antivir Ther. 2004 Oct;9(5):679-93.
A meeting of physicians and scientists involved in the management of chronic hepatitis B (CHB) was held to review current scientific data regarding antiviral resistance in hepatitis B virus (HBV) infection. The goals of the meeting were to describe current treatments for CHB, discuss emerging issues in HBV drug resistance and to delineate patient monitoring, including markers for resistance, during administration of antiviral therapy. The aim of this review article is to provide treating physicians with a framework for the management of CHB in the context of antiviral resistance. Definitions of primary and secondary antiviral treatment failure can be used to aid monitoring and early diagnosis of drug resistance before disease progression occurs as a consequence of viral breakthrough. Primary antiviral treatment failure is defined as failure of a drug to reduce HBV DNA levels by > or = 1 x log10 IU/ml within 3 months following initiation of therapy, and secondary antiviral treatment failure as a rebound of HBV replication of > or = 1 x log10 IU/ml from nadir in patients with an initial antiviral treatment effect (> or = 1 x log10 IU/ml decrease in serum HBV DNA). Confirmation of antiviral drug failure can be established by sequencing the HBV DNA polymerase and identifying specific genetic markers of antiviral drug resistance. In addition to virological assays, HBV resistance can be assessed from a clinical perspective including increased serum alanine aminotransferase levels and the development of systemic symptoms or signs of liver failure. Potential strategies to prevent the emergence of resistance and how to manage drug-resistant HBV once it emerges are discussed.
一场由参与慢性乙型肝炎（CHB）管理的医生和科学家们召开的会议举行了，旨在回顾关于乙型肝炎病毒（HBV）感染中抗病毒耐药性的当前科学数据。该会议的目标是描述CHB的当前治疗方法，讨论HBV耐药性方面出现的新问题，并阐述在抗病毒治疗期间的患者监测，包括耐药性标志物。这篇综述文章的目的是为治疗医生提供一个在抗病毒耐药背景下管理CHB的框架。原发性和继发性抗病毒治疗失败的定义可用于在病毒突破导致疾病进展之前辅助监测和早期诊断耐药性。原发性抗病毒治疗失败定义为在治疗开始后3个月内一种药物未能将HBV DNA水平降低≥1×log10 IU/ml，继发性抗病毒治疗失败定义为在初始抗病毒治疗有效果（血清HBV DNA降低≥1×log10 IU/ml）的患者中，HBV复制从最低点反弹≥1×log10 IU/ml。通过对HBV DNA聚合酶进行测序并识别抗病毒药物耐药性的特定基因标志物，可以确定抗病毒药物失败。除了病毒学检测外，还可以从临床角度评估HBV耐药性，包括血清丙氨酸氨基转移酶水平升高以及出现全身症状或肝衰竭体征。文中讨论了预防耐药性出现的潜在策略以及耐药HBV出现后如何进行管理。
