乙型肝炎病毒亚型对核苷治疗乙型肝炎e抗原阳性患者抗病毒

StephenW

Hepatol Res. 2017 Apr 19. doi: 10.1111/hepr.12907. [Epub ahead of print]
Effect of hepatitis B virus subgenotype on antiviral response in nucleoside-treated hepatitis B e antigen-positive patients.
Shen S1, Liang X1, Hamed K2, Tanaka Y3, Omagari K3, Fan R1, Xie Q4, Tan D5, Zhou B1, Jia JD6, Hou J1, Sun J1.
Author information

1    Department of Infectious Diseases, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2    Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
3    Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Science, Nagoya, Japan.
4    Department of Infectious Diseases, Ruijin Hospital, Shanghai.
5    Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha.
6    Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Abstract
BACKGROUND:

Previous studies have reported that hepatitis B virus (HBV) genotype is not a predictor of treatment response with nucleos(t)ide analogue (NUC) therapy. However, the impact of subgenotype on treatment response is unknown.
AIM:

To identify the effect of HBV subgenotype on treatment response.
METHODS:

In this retrospective study, the derivation dataset comprised patients from the EFFORT study (NCT00962533) telbivudine monotherapy group; patients infected with genotypes B or C from the GLOBE (NCT00057265) and 015 (NCT00131742) studies formed the validation dataset. HBV subgenotype was determined using phylogenetic analysis based on the surface or overlapping polymerase gene. Molecular modeling was used to investigate relationships between positions of the substitutions within reverse transcriptase and genotypic resistance.
RESULTS:

Of the patients in the derivation dataset, 110, 24, 162, and 1 patients were classified as having HBV subgenotypes B2, C1, C2, or other, respectively, compared to 222, 146, 282, and 51 in the validation dataset. Patients infected with subgenotype C1 showed higher virologic response rate and hepatitis B e antigen (HBeAg) seroconversion rate, and lower genotypic resistance rate than those infected with subgenotypes B2 and C2. Patients with genotypic resistance to telbivudine with subgenotype C1 showed fewer secondary mutations. The crystal structure model of reverse transcriptase showed that these secondary mutations were located around the YMDD motif, which possibly influenced the chance of mutations at rtM204.
CONCLUSION:

HBV subgenotype C1 is associated with better antiviral response to NUCs in HBeAg-positive patients than B2 and C2. The exact mechanism needs to be explored further.

This article is protected by copyright. All rights reserved.
KEYWORDS:

viral hepatology

PMID:
    28422442
DOI:
    10.1111/hepr.12907

StephenW

Hepatol Res。 2017年4月19日。doi：10.1111 / hepr.12907。 [提前印刷]
乙型肝炎病毒亚型对核苷治疗乙型肝炎e抗原阳性患者抗病毒反应的影响。
沉S1，梁X1，Hamed K2，田中Y3，Omagari K3，Fan R1，谢Q4，Tan D5，Zhou B1，Jia JD6，Hou J1，Sun J1。
作者信息

1广东省南方医科大学南方医院广东省病毒性肝炎病毒重点实验室器官功能衰竭研究国家重点实验室1传染病司。
2 Novartis Pharmaceuticals Corporation，East Hanover，New Jersey，USA。
3名古屋市立大学医学系研究科病毒学与肝病科，日本名古屋市。
4上海瑞金医院传染病科。
5中南大学湘雅医院感染科，长沙。
中国北京首都医科​​大学北京友谊医院肝脏研究中心6号。

抽象
背景：

以前的研究报道，乙型肝炎病毒（HBV）基因型不是核型（t）ide类似物（NUC）治疗的治疗反应的预测因子。然而，亚型对治疗反应的影响是未知的。
目标：

确定HBV亚基因型对治疗反应的影响。
方法：

在这项回顾性研究中，推导数据集包括EFFORT研究（NCT00962533）替比夫定单药治疗组患者;感染GLOBE（NCT00057265）和015（NCT00131742）研究的基因型B或C的患者形成了验证数据集。使用基于表面或重叠聚合酶基因的系统发育分析确定HBV亚型。分子模拟用于研究逆转录酶和基因型抗性之间取代位置之间的关系。
结果：

在推导数据集中，与验证数据集中的222,146,282和51相比，分别将110,24,162和1例患者分为HBV亚基因型B2，C1，C2或其他。感染亚型C1的患者比感染亚基因型B2和C2的病毒学应答率和乙型肝炎e抗原（HBeAg）血清转化率更高，基因型耐药率低。对具有亚型C1的替比夫定具有基因型耐药性的患者显示较少的次要突变。逆转录酶的晶体结构模型显示，这些次级突变位于YMDD基序周围，这可能影响rtM204突变的机会。
结论：

乙型肝炎病毒亚基因型C1与HBeAg阳性患者相比，具有比B2和C2更好的对NUCs的抗病毒反应。需要进一步探讨确切的机制。

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关键词：

病毒性肝病学

PMID：
    28422442
DOI：
    10.1111 / hepr.12907