Evolution of hepatitis B virus polymerase and surface genes in patients receiving finite antiviral therapy.

IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Journal of Gastroenterology and Hepatology Pub Date : 2024-11-05 DOI:10.1111/jgh.16791
Yu-De Chu, Chao-Wei Hsu, Pei-Huan Ho, Chih-Yung Chiou, Chih-Lang Lin, Kung-Hao Liang, Ming-Wei Lai, Chau-Ting Yeh
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Abstract

Background and aim: Hepatitis B virus (HBV) reactivation could develop after withdrawal following a finite course of nucleoside analog (NA) therapy, leading to virological and clinical relapses. The genetic heterogeneity in the HBV surface and polymerase genes during finite NA therapy has not been carefully studied.

Methods: Seven chronic HBV-infected patients experiencing relapses following entecavir (ETV; n = 5; Patients 1 to 5) or tenofovir disoproxil fumarate (TDF; n = 2; Patients 6 and 7) withdrawal were included. Sera obtained before treatment and at relapses were retrieved and submitted for DNA extraction and amplicon-specific deep sequencing.

Results: ETV-treated patients had a longer time-to-relapse than that of TDF-treated patients (P = 0.0357). No drug-resistance related polymerase mutation was detected during relapses, except for a low percentage (1.4%) of rtM204I mutation in Patient 1. Two surface truncation mutations (sW216*; 40.9% and sW182*; 4.7%) detected before treatment in two TDF-treated patients (Patients 6 and 7, respectively) were overtaken by the wild types during subsequent drug-withdrawal-related relapses. The simultaneous presence of sG44E (T-cell epitope) and sE164G (B-cell epitope) mutations was associated with failure of HBV e antigen (HBeAg) seroclearance in ETV-treated patients.

Conclusions: In conclusion, HBV genome continues to evolve during the courses of finite antiviral therapies. Pre-existing surface truncation mutations can be overtaken by the wild types after relapses. The sG44E/sE164G mutations are associated with failure of HBeAg seroclearance.

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接受有限抗病毒治疗的患者体内乙型肝炎病毒聚合酶和表面基因的演变。
背景和目的:乙型肝炎病毒(HBV)可能在核苷类似物(NA)治疗的有限疗程后出现再激活,导致病毒学和临床复发。目前尚未仔细研究在有限的 NA 治疗过程中 HBV 表面基因和聚合酶基因的遗传异质性:方法:纳入了七名在恩替卡韦(ETV;n = 5;患者 1 至 5)或富马酸替诺福韦二吡呋酯(TDF;n = 2;患者 6 和 7)停药后复发的慢性 HBV 感染者。采集治疗前和复发时的血清,并进行DNA提取和扩增子特异性深度测序:结果:ETV治疗患者的复发时间长于TDF治疗患者(P = 0.0357)。在复发过程中,除了患者1的rtM204I突变比例较低(1.4%)外,未检测到与耐药性相关的聚合酶突变。在两名接受过 TDF 治疗的患者(患者 6 和 7,分别为 40.9% 和 4.7%)中,治疗前检测到两个表面截断突变(sW216*;40.9% 和 sW182*;4.7%),但在随后与停药相关的复发中被野生型取代。同时出现的sG44E(T细胞表位)和sE164G(B细胞表位)突变与ETV治疗患者的HBV e抗原(HBeAg)血清清除失败有关:总之,在有限的抗病毒治疗过程中,HBV 基因组仍在不断进化。复发后,原有的表面截断突变可被野生型取代。sG44E/sE164G突变与HBeAg血清清除失败有关。
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来源期刊
CiteScore
7.90
自引率
2.40%
发文量
326
审稿时长
2.3 months
期刊介绍: Journal of Gastroenterology and Hepatology is produced 12 times per year and publishes peer-reviewed original papers, reviews and editorials concerned with clinical practice and research in the fields of hepatology, gastroenterology and endoscopy. Papers cover the medical, radiological, pathological, biochemical, physiological and historical aspects of the subject areas. All submitted papers are reviewed by at least two referees expert in the field of the submitted paper.
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