Melbourne University, Vic., Australia.
Bull World Health Organ. 2010 Jan;88(1):66-73. doi: 10.2471/BLT.08.065722. Epub 2009 Oct 23.
Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.
自乙肝疫苗广泛应用以来，它已成为全球婴儿免疫计划的重要组成部分。对于乙型肝炎病毒相关肝细胞癌发病率较高的国家，乙肝疫苗尤其重要。1998 年，拉米夫定（首个核苷类似物药物）问世，在此之前，慢性乙型肝炎感染者的有效治疗选择有限。然而，作为单一治疗药物，拉米夫定存在一个显著的缺点：它会诱导出对全球乙肝免疫计划构成威胁的拉米夫定耐药乙肝病毒株。与药物治疗相关的突变会导致表面抗原蛋白发生变化，而表面抗原蛋白正是乙肝疫苗所模拟的病毒的精确部分。然而，在接受治疗的患者中，与抗病毒药物相关的潜在疫苗逃逸突变体（ADAP-VEMs）的出现并不一定会对全球乙肝免疫计划构成重大、迫在眉睫的威胁。尽管如此，已有证据表明，目前的治疗方案已经导致了稳定的 ADAP-VEMs 的选择。目前的治疗旨在预防乙型肝炎病毒感染的长期并发症，而很少考虑潜在的公共卫生不良影响。为了解决个人和公共卫生方面的担忧，迫切需要开展试验，以找到既能有效又不会诱导 ADAP-VEMs 出现的现有药物的最佳组合。本文研究了抗病毒药物选择对影响表面抗原的病毒基因组部分的改变机制，并探讨了其对当前乙肝免疫计划的潜在影响。
