HBeAg阳性慢性乙型肝炎患者接受聚乙二醇干扰素-α治疗后，

StephenW

Higher baseline viral diversity correlates with lower HBsAg decline following PEGylated interferon-alpha therapy in patients with HBeAg-positive chronic hepatitis B
         

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Authors Li H, Zhang L, Ren H, Hu P

Received 25 January 2018

Accepted for publication 20 March 2018

Published 3 May 2018 Volume 2018:11 Pages 671—680

DOI https://doi.org/10.2147/IDR.S163765

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Varun Dwivedi

Peer reviewer comments 3

Editor who approved publication: Dr Joachim Wink

Hu Li, Li Zhang, Hong Ren, Peng Hu

Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China

Background: Viral diversity seems to predict treatment outcomes in certain viral infections. The aim of this study was to evaluate the association between baseline intra-patient viral diversity and hepatitis B surface antigen (HBsAg) decline following PEGylated interferon-alpha (Peg-IFN-α) therapy.
Patients and methods: Twenty-six HBeAg-positive patients who were treated with Peg-IFN-α were enrolled. Nested polymerase chain reaction (PCR), cloning, and sequencing of the hepatitis B virus S gene were performed on baseline samples, and normalized Shannon entropy (Sn) was calculated as a measure of small hepatitis B surface protein (SHBs) diversity. Multiple regression analysis was used to estimate the association between baseline Sn and HBsAg decline.
Results: Of the 26 patients enrolled in the study, 65.4% were male and 61.5% were infected with hepatitis B virus genotype B. The median HBsAg level at baseline was 4.5 log10 IU/mL (interquartile range: 4.1–4.9) and declined to 3.0 log10 IU/mL (interquartile range: 1.7–3.9) after 48 weeks of Peg-IFN-α treatment. In models adjusted for baseline alanine aminotransferase (ALT) and HBsAg, the adjusted coefficients (95% CI) for ΔHBsAg and relative percentage HBsAg decrease were −1.3 (−2.5, −0.2) log10 IU/mL for higher SHBs diversity (Sn≥0.58) patients and −26.4% (−50.2%, −2.5%) for lower diversity (Sn<0.58) patients. Further analysis showed that the “a” determinant upstream flanking region and the first loop of the “a” determinant (nucleotides 341–359, 371–389, and 381–399) were the main sources of higher SHBs diversity.
Conclusion: Baseline intra-patient SHBs diversity was inverse to HBsAg decline in HBeAg-positive chronic hepatitis B (CHB) patients receiving Peg-IFN-α monotherapy. Also, more sequence variations within the “a” determinant upstream flanking region and the first loop of the “a” determinant were the main sources of the higher SHBs diversity.

Keywords: HBsAg decline, viral diversity, Shannon entropy, interferon, chronic hepatitis B

StephenW

HBeAg阳性慢性乙型肝炎患者接受聚乙二醇干扰素-α治疗后，基线病毒多样性较高与HBsAg下降相关
         

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    度量

作者李，张立仁H胡鹏

收到2018年1月25日

接受公布2018年3月20日

发布于2018年5月3日卷2018年：11页671-680

DOI https://doi.org/10.2147/IDR.S163765

检查剽窃是的

单盲评审

同行评审由Varun Dwivedi博士批准

同行评审意见3

编辑批准出版物：Joachim Wink博士

胡莉李章洪仁彭虎

重庆医科大学附属第二医院病毒性肝炎研究所传染病研究所传染病分子生物学教育部重点实验室

背景：病毒多样性似乎预测了某些病毒感染的治疗结果。本研究的目的是评估PEG化干扰素-α（Peg-IFN-α）治疗后基线患者病毒多样性与乙型肝炎表面抗原（HBsAg）下降之间的关系。
患者和方法：入组26例接受Peg-IFN-α治疗的HBeAg阳性患者。对基线样本进行巢式聚合酶链式反应（PCR），克隆和测序乙型肝炎病毒S基因，并且将归一化香农熵（Sn）计算为小型乙型肝炎表面蛋白（SHB）多样性的量度。使用多元回归分析来估计基线Sn与HBsAg下降之间的关联。
结果：入选研究的26名患者中，65.4％为男性，61.5％感染乙型肝炎病毒基因型B.基线时HBsAg水平中位数为4.5 log10 IU / mL（四分位间距范围：4.1-4.9） Peg-IFN-α治疗48周后的log 10 IU / mL（四分位数间距：1.7-3.9）。在校正基线丙氨酸转氨酶（ALT）和HBsAg的模型中，对于较高SHBs多样性，ΔHBsAg和相对百分比HBsAg降低的校正系数（95％CI）分别为-1.3（-2.5，-0.2）log10 IU / mL（Sn≥0.58 ），多样性较低（Sn <0.58）的患者为-26.4％（-50.2％，-2.5％）。进一步分析表明，“a”决定簇上游侧翼区和“a”决定簇（核苷酸341-359,371-389和381-399）的第一环是高SHB多样性的主要来源。
结论：接受Peg-IFN-α单药治疗的HBeAg阳性慢性乙型肝炎（CHB）患者的基线患者SHBs多样性与HBsAg下降相反。此外，“a”决定上游侧翼区域和“a”决定簇的第一环内更多的序列变异是更高SHB多样性的主要来源。

关键词：HBsAg下降，病毒多样性，Shannon熵，干扰素，慢性乙型肝炎