Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment
Naturally occurring deletion/insertion mutations within HBV whole genome sequences in HBeAg-positive chronic hepatitis B patients are correlated with baseline serum HBsAg and HBeAg levels and might predict a shorter interval to HBeAg loss and seroconversion during antiviral treatment
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DOI：
10.1016/j.meegid.2015.05.013
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发表时间：
2015-07-01
影响因子：
3.2
通讯作者：
Li, Tong
中科院分区：
文献类型：
--
作者：
Hao, Ran;Xiang, Kuanhui;Li, Tong
目的：对于HBeAg阳性的慢性B肝炎（CHB）患者，整个B肝炎病毒（HBV）基因组的缺失/插入（Del/Ins）尚未得到充分研究。本研究的目的是在抗病毒基线时描述这些患者全长基因组准种序列中的HBV Del/Ins突变，并揭示其对HBV血清学标志物和对核苷（酸）类似物（NUC）治疗反应的潜在影响。共有30例HBeAg阳性的C基因型慢性乙型肝炎患者接受了104周的拉米夫定（LMV）和阿德福韦酯（ADV）治疗，联合治疗。对基线时血清样本中HBV全基因组序列进行克隆测序，并使用生物信息学工具进行分析。在306个未剪接的克隆序列中，61.8%（189/306）存在Del/Ins突变，38.2%（117/306）为不含Del/Ins的全长基因组。我们鉴定了55个携带Del/Ins的HBV基因组模式，它们影响单个或多个功能基因组区域。在基线时，Del/Ins阳性克隆比例与HBsAg（r =-0.3985，P = 0.0292）和HBeAg（r =-0.3878，P = 0.0342）呈显著负相关。结论：抗病毒治疗前HBeAg阳性的CHB患者中，HBV全基因组Del/Ins突变普遍存在，而Del/Ins突变的发生与HBeAg转阴和血清转换的间隔时间有关。基线时这些突变的检出率较高可能与LMV和ADV联合治疗的反应较好相关。(C)2015 Elsevier B. V.版权所有。
Objectives: Deletion/insertion (Del/Ins) throughout hepatitis B virus (HBV) genome has not been well studied for HBeA-positive chronic hepatitis B (CHB) patients. This study aimed to characterize the HBV Del/Ins mutations in full-length genome quasispecies sequences in such patients at antiviral baseline and to reveal their potential impacts on HBV serological markers and responses to nucleos(t)ide analogue (NUC) treatment.Materials and methods: A total of 30 HBeAg-positive CHB patients with genotype C infection receiving a 104-week lamivudine (LMV) and adefovir dipivoxil (ADV) combination therapy were enrolled. HBV whole genome sequences in serum samples at baseline were clone sequenced and analyzed using bioinformatics tools.Results: Among 306 unspliced clone sequences, 61.8% (189/306) had Del/Ins mutations, 38.2% (117/306) were full-length genomes without any Del/Ins. Due to different combinations of 125 deletion types and 45 insertion types, we identified 55 Del/Ins-harboring HBV genome patterns, which affected a single or several functional genomic regions. Importantly, the proportion of Del/Ins-harboring clones was found to be significantly negatively correlated with HBsAg (r = -0.3985, P = 0.0292) and HBeAg (r = -0.3878, P = 0.0342) at baseline. Higher percentage of Del/Ins-harboring clones at baseline was found to predict a shorter interval to HBeAg loss and seroconversion.Conclusion: Del/Ins mutations within HBV whole genome were prevalent in HBeAg-positive CHB patients prior to antiviral treatment. A higher detection rate of these mutations at baseline might correlate with a better response to LMV and ADV combination therapy. (C) 2015 Elsevier B.V. All rights reserved.