The aim of this study was to assess the frequencies and patterns of naturally occurring genotypic resistance to nucleos(t)ide analogues (NUCs) and typical hepatitis B surface antigen (HBsAg) amino acid substitutions in naive hemodialysis (HD) patients with chronic hepatitis B. In order to achieve this, the genotypic resistance to NUCs and HBsAg amino acid substitutions were classified into primary/compensatory resistance mutation and antiviral drug-associated potential vaccine-escape mutation (ADAPVEM)/typical HBsAg amino acid substitution, respectively. Direct sequencing of polymerase (pol) gene of hepatitis B virus (HBV) was performed on DNA samples obtained from 248 HBsAg-positive Turkish patients. Overall, 38% (n = 94) of HBsAg-positive HD patients had detectable HBV DNA in their serum. Naturally occurring primary and compensatory resistance mutations to NUCs were detected in 30% (n = 28) and 52% (n = 49) of HD patients, respectively. However, 6 types of ADAPVEMs and 48 types of typical HBsAg amino acid substitutions were found in 10.6% (n = 10) and 46% (n = 43) of the HD patients, respectively. Our study suggests that every HD patient diagnosed with chronic hepatitis B, who is a potential candidate for NUCs treatment, should also be monitored for the baseline pol gene sequence changes before the initial treatment, for a more effective management of future treatment options. Further, a relatively higher frequency of ADAPVEMs variants needs to be addressed as a public health problem.

译文

这项研究的目的是评估天然发生的基因型对核苷 (酸) 类似物 (NUCs) 和典型乙型肝炎表面抗原 (HBsAg) 氨基酸替代的频率和模式在幼稚血液透析 (HD) 患者慢性乙型肝炎。为了实现这一目标,将对NUCs和HBsAg氨基酸取代的基因型抗性分别分为原发性/代偿性耐药突变和抗病毒药物相关潜在的疫苗逃逸突变 (ADAPVEM)/典型HBsAg氨基酸取代。乙型肝炎病毒 (HBV) 的聚合酶 (pol) 基因的直接测序是从248 HBsAg阳性土耳其患者获得的DNA样品。总体而言,38% (n = 94) HBsAg阳性HD患者的血清中可检测到HBV DNA。分别在30% (n = 28) 和52% (n = 49) 的HD患者中检测到自然发生的对NUCs的原发性和代偿性耐药突变。然而,在HD患者的10.6% (n = 10) 和46% (n = 43) 中分别发现了6种类型的ADAPVEMs和48种类型的典型HBsAg氨基酸取代。我们的研究表明,每个HD患者诊断为慢性乙型肝炎,谁是NUCs治疗的潜在候选者,也应该监测基线pol基因序列变化之前的初始治疗,以更有效地管理未来的治疗选择。此外,需要将相对较高的ADAPVEMs变体频率作为公共卫生问题来解决。

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