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儿童患者聚乙二醇化干扰素-α-2a治疗后乙肝病毒准种特征与乙肝表面抗原血清学转换的相关性

Association of characteristics of HBV quasispecies with hepatitis B surface antigen seroconversion after pegylated interferon-α-2a treatment in child patients.

作者信息

Yang Juncheng, Yang Guifeng, He Haitang, Ning Lu, Liu Zhihua, Fu Qunfang, Chen Haitao, Deng Haohui, Wang Zhanhui, Luo Kangxian

机构信息

Department of Infectious Diseases and Hepatology Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.

出版信息

Antivir Ther. 2018;23(7):567-574. doi: 10.3851/IMP3262. Epub 2018 Aug 10.

DOI:10.3851/IMP3262
PMID:30095435
Abstract

BACKGROUND

The correlation between hepatitis B surface antigen (HBsAg) seroconversion and the characteristics of HBV quasispecies (QS) before and during pegylated interferon-α-2a (PEG-IFN-α-2a) treatment in hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) children has not yet been reported.

METHODS

35 patients, including 18 HBsAg seroconverters (SS) and 17 non-seroconverters (SN), were enrolled. Serum samples were collected before treatment and at weeks 12 and 24 of treatment. Sequences within the basal core promoter/pre-core (BCP/PC) and S/reverse transcriptase (S/RT) region were analysed by next-generation sequencing.

RESULTS

There was no significant difference in the baseline diversity of HBV QS (Shannon entropy [Sn]; Hamming distance [HD]) in either region between the two groups. The baseline mutations A1762T/G1764A, C1913A, and T2003A/G or C2004T were correlated with non-response to therapy (P=0.025, P=0.036, P=0.032, respectively). After 24 weeks of therapy, HBV diversity within the BCP/PC region in the SS group notably declined (Sn: P=0.002; HD: P=0.011), while that of the SN group was nearly unchanged. As for the S/RT region, 24 weeks of treatment made no significant difference on QS diversity in either group.

CONCLUSIONS

Our data demonstrated that the baseline viral mutations and dynamic changes in HBV QS diversity within the BCP/PC region were closely related to HBsAg seroconversion in HBeAg-positive CHB children treated with PEG-IFN-α-2a.

摘要

背景

在乙肝e抗原(HBeAg)阳性的慢性乙型肝炎(CHB)儿童中,聚乙二醇化干扰素-α-2a(PEG-IFN-α-2a)治疗前及治疗期间乙肝表面抗原(HBsAg)血清学转换与乙肝病毒准种(QS)特征之间的相关性尚未见报道。

方法

纳入35例患者,其中18例为HBsAg血清学转换者(SS),17例为非血清学转换者(SN)。在治疗前以及治疗第12周和第24周采集血清样本。通过二代测序分析核心启动子/前核心(BCP/PC)和S/逆转录酶(S/RT)区域内的序列。

结果

两组在任一区域的HBV QS基线多样性(香农熵[Sn];汉明距离[HD])均无显著差异。基线突变A1762T/G1764A、C1913A以及T2003A/G或C2004T与治疗无应答相关(分别为P=0.025、P=0.036、P=0.032)。治疗24周后,SS组BCP/PC区域内的HBV多样性显著下降(Sn:P=0.002;HD:P=0.011),而SN组几乎未变。至于S/RT区域,治疗24周后两组的QS多样性均无显著差异。

结论

我们的数据表明,在接受PEG-IFN-α-2a治疗的HBeAg阳性CHB儿童中,BCP/PC区域内的基线病毒突变和HBV QS多样性的动态变化与HBsAg血清学转换密切相关。

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