Nuffield Department of Medicine, Oxford, UK.
Division of Infectious Diseases & Global Public Health, Department of Medicine, University of California, San Diego, CA, USA.
J Viral Hepat. 2021 Aug;28(8):1110-1120. doi: 10.1111/jvh.13525. Epub 2021 May 7.
Vaccination and anti-viral therapy with nucleos(t)ide analogues (NAs) are key approaches to reducing the morbidity, mortality and transmission of hepatitis B virus (HBV) infection. However, the efficacy of these interventions may be reduced by the emergence of drug resistance-associated mutations (RAMs) and/or vaccine escape mutations (VEMs). We have assimilated data on the global prevalence and distribution of HBV RAMs/VEMs from publicly available data and explored the evolution of these mutations. We analysed sequences downloaded from the HBV Database and calculated prevalence of 41 RAMs and 38 VEMs catalogued from published studies. We generated maximum likelihood phylogenetic trees and used treeBreaker to investigate the distribution and estimated the age of selected mutations across tree branches. RAM M204I/V had the highest prevalence, occurring in 3.8% (109/2838) of all HBV sequences in our data set, and a significantly higher rate in genotype C at 5.4% (60/1102, p = 0.0007). VEMs had an overall prevalence of 1.3% (37/2837) and had the highest prevalence in genotype C and in Asia at 2.2% (24/1102; p = 0.002) and 1.6% (34/2109; p = 0.009), respectively. Phylogenetic analysis suggested that RAM/VEMs can arise independently of treatment/vaccine exposure. In conclusion, HBV RAMs/VEMs have been found globally and across genotypes, with the highest prevalence observed in genotype C. Screening for genotype and for resistance-associated mutations may help to improve stratified patient treatment. As NAs and HBV vaccines are increasingly being deployed for HBV prevention and treatment, monitoring for resistance and advocating for better treatment regimens for HBV remains essential.
接种疫苗和使用核苷（酸）类似物（NAs）进行抗病毒治疗是降低乙型肝炎病毒（HBV）感染发病率、死亡率和传播率的关键方法。然而，耐药相关突变（RAMs）和/或疫苗逃逸突变（VEMs）的出现可能会降低这些干预措施的疗效。我们从公开数据中整合了有关全球 HBV RAMs/VEMs 流行率和分布的数据，并探讨了这些突变的演变。我们分析了从 HBV 数据库下载的序列，并计算了从已发表研究中分类的 41 种 RAM 和 38 种 VEM 的流行率。我们生成最大似然系统发育树，并使用 TreeBreaker 来研究分布情况，并估计选定突变在树分支上的年龄。RAM M204I/V 的流行率最高，在我们数据集中所有 HBV 序列的 3.8%（109/2838）中发生，在基因型 C 中发生率更高，为 5.4%（60/1102，p=0.0007）。VEMs 的总体流行率为 1.3%（37/2837），在基因型 C 和亚洲的流行率最高，分别为 2.2%（24/1102；p=0.002）和 1.6%（34/2109；p=0.009）。系统发育分析表明，RAM/VEMs 的出现可以独立于治疗/疫苗暴露。总之，HBV RAMs/VEMs 已在全球范围内和各基因型中发现，在基因型 C 中观察到的流行率最高。对基因型和耐药相关突变的筛查可能有助于改善分层患者的治疗。随着 NAs 和 HBV 疫苗越来越多地用于 HBV 的预防和治疗，监测耐药性并倡导更好的 HBV 治疗方案仍然至关重要。
