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真的血液透析(HD)慢性肝炎患者对核苷酸(t)核苷酸类似物(NUCs)和典型的乙型肝炎表面抗原(HBsAg)氨基酸替代的天然基因型耐药的频率和模式B.为了实现这一点,分别将对NUCs和HBsAg氨基酸替代的基因型抗性分为原发性/代偿性抗性突变和抗病毒药物相关的潜在疫苗逃逸突变(ADAPVEM)/典型的HBsAg氨基酸替代。乙型肝炎病毒(HBV)的聚合酶(pol)基因的直接测序是从248例HBsAg阳性土耳其患者获得的DNA样品上进行的。总体上,有38%(n = 94)的HBsAg阳性HD患者血清中可检测到HBV DNA。分别在30%(n = 28)和52%(n = 49)的HD患者中检测到对NUC的自然发生的原发性和代偿性耐药突变。然而,在HD患者中分别发现了6种类型的ADAPVEM和48种典型的HBsAg氨基酸取代,分别为10.6%(n = 10)和46%(n = 43)。我们的研究表明,每位被诊断患有慢性乙型肝炎的HD患者(可能是NUCs治疗的候选人)也应在初次治疗前接受基线pol基因序列变化的监测,以更有效地管理未来的治疗方案。此外,作为公共卫生问题,需要解决相对较高频率的ADAPVEM变体的问题。

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