Konopleva Maria V, Belenikin Maxim S, Shanko Andrei V, Bazhenov Alexey I, Kiryanov Sergei A, Tupoleva Tatyana A, Sokolova Maria V, Pronin Alexander V, Semenenko Tatyana A, Suslov Anatoly P
Federal State Budget Institution "National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N.F. Gamaleya" of the Ministry of Health of the Russian Federation, 123098 Moscow, Russia.
Laboratory of Molecular Medical Diagnostics, Moscow Institute of Physics and Technology, State University, 141701 Dolgoprudny, Russia.
Diagnostics (Basel). 2021 May 27;11(6):969. doi: 10.3390/diagnostics11060969.
Multiple studies of hepatitis B virus (HBV) genetic variability and its relationship with the disease pathogenesis are currently ongoing, stemming from growing evidence of the clinical significance of HBV mutations. It is becoming increasingly evident that patients with hematologic malignancies may be particularly prone to a higher frequency of such mutations. The present report is the first extensive study of the prevalence of escape mutations in S-HBsAg, performed using isolates from 59 patients from hospital hematology departments with diagnoses of leukemia (n = 32), lymphoma (n = 20), multiple myeloma (n = 3), and non-tumor blood diseases (n = 4). The isolates were serologically examined for the presence of HBV markers and sequenced using either next-generation sequencing (NGS) or Sanger sequencing. Occult hepatitis B was found in 5.1% of cases. Genetic analysis of the region corresponding to S-HBsAg demonstrated an exceptionally high mutation frequency in patients with leukemias (93.4%) and lymphomas (85.0%), along with the prominent mutation heterogeneity. Additionally, more than 15 mutations in one sample were found in patients with leukemias (6.3% of cases) and lymphomas (5.0% of cases). Most of the mutations were clinically significant. The study analyzes the mutation profile of HBV in different oncohematological diseases and the frequency of individual mutations. The data strongly suggest that the NGS method, capable of detecting minor populations of HBV mutations, provides a diagnostic advantage, lays the foundation for the development of screening methods, and allows for the study of the virological and pathogenetic aspects of hepatitis B.
目前正在进行多项关于乙型肝炎病毒(HBV)基因变异性及其与疾病发病机制关系的研究,这源于越来越多关于HBV突变临床意义的证据。越来越明显的是,血液系统恶性肿瘤患者可能特别容易出现此类突变的较高频率。本报告是首次对S-HBsAg逃逸突变的患病率进行的广泛研究,该研究使用了来自医院血液科的59例患者的分离株,这些患者被诊断为白血病(n = 32)、淋巴瘤(n = 20)、多发性骨髓瘤(n = 3)和非肿瘤性血液疾病(n = 4)。对分离株进行血清学检测以确定HBV标志物的存在,并使用下一代测序(NGS)或桑格测序进行测序。在5.1%的病例中发现了隐匿性乙型肝炎。对与S-HBsAg对应的区域进行基因分析显示,白血病患者(93.4%)和淋巴瘤患者(85.0%)的突变频率异常高,且突变具有显著的异质性。此外,白血病患者(6.3%的病例)和淋巴瘤患者(5.0%的病例)的一个样本中发现了超过15个突变。大多数突变具有临床意义。该研究分析了不同血液肿瘤疾病中HBV的突变谱以及单个突变的频率。数据强烈表明,能够检测HBV突变小群体的NGS方法具有诊断优势,为筛查方法的开发奠定了基础,并有助于研究乙型肝炎的病毒学和发病机制方面。