在慢性乙型肝炎中鉴定的氨基酸组成的亚组特异性差异

StephenW

September 20, 2018
Subgroup-Specific Differences in Amino Acid Composition Identified in Chronic Hepatitis B


Sequence Harmony was used to identify common sites between the subgroups of HBeAg status and between those with response and non-response to therapy. Sequence Harmony was used to identify common sites between the subgroups of HBeAg status and between those with response and non-response to therapy.

A number of different subgroup-specific sites have been observed between individuals with chronic hepatitis B who are HBeAg positive or negative, as well as between individuals who are responsive and unresponsive to peginterferon/adefovir combination therapy. This study was recently published in Antiviral Research.

This study included 89 individuals with chronic hepatitis B, 42 of whom were HBeAg positive and 47 of whom were HBeAg negative. Sequence Harmony identified 54 sites with scores below 0.960, indicating areas where the 2 study groups diverge in amino acid composition (Z-scores <-0.8; ≥50 reads).

Additionally, Sequence Harmony showed 22 sites where HBc amino acids differed between HBeAg negative with and without response to treatment (Z-scores <-0.8; ≥50 reads). HBeAg-negative participants showed significantly higher median amino acid variation in certain sites than other groups.

This trend showed a negative correlation with levels of HBsAg and HBV DNA. Both HBV genotype and the presence of BCP mutations were revealed via multivariable regression to be independent of the association between HBeAg negative status and increased amino acid non-consensus.

Initially, 92 patients with chronic hepatitis B received 48 weeks of treatment with weekly subcutaneous peginterferon alfa-2a 180 μg and daily adefovir dipivoxil 10 mg. Of these, 84 completed both treatment and 2 years of follow-up.

At week 72 of post-treatment follow-up, participants were assessed for achievement of combined response, which included HBV DNA levels ≤2000 IL/mL, negative HBeAg status, and sustained normal levels of alanine aminotransferase. Sequence Harmony was used to identify common sites between the subgroups of HBeAg status and between those with response and non-response to therapy.


The study researchers conclude that "Sequence Harmony identified a number of amino acid changes associated with HBeAg-status and response to peginterferon/adefovir combination therapy."

Disclosures: This study was funded by Roche the Netherlands.
Reference

van der Ree MH, Jansen L, Welkers MRA, Reesink HW, Feenstra KA, Kootstra NA. Deep sequencing identifies hepatitis B virus core protein signatures in chronic hepatitis B patients [published online August 16, 2018]. Antiviral Res. doi: 10.1016/j.antiviral.2018.08.009

StephenW

2018年9月20日
在慢性乙型肝炎中鉴定的氨基酸组成的亚组特异性差异


序列和谐用于识别HBeAg状态亚组之间以及对治疗有反应和无应答的亚组之间的共同位点。序列和谐用于识别HBeAg状态亚组之间以及对治疗有反应和无应答的亚组之间的共同位点。

在HBeAg阳性或阴性的慢性乙型肝炎患者之间以及对聚乙二醇干扰素/阿德福韦联合治疗有反应和无反应的个体之间观察到许多不同的亚组特异性位点。该研究最近发表在抗病毒研究中。

本研究纳入89例慢性乙型肝炎患者，其中42例为HBeAg阳性，47例为HBeAg阴性。序列和谐鉴定了54个具有低于0.960的分数的位点，表明2个研究组在氨基酸组成上不同的区域（Z分数<-0.8;≥50个读数）。

此外，序列和谐显示22个位点，其中HBcAg阴性的HBc氨基酸在治疗反应和不治疗反应之间存在差异（Z-分数<-0.8;≥50读数）。 HBeAg阴性参与者在某些部位的氨基酸中位数变异显着高于其他组。

这一趋势与HBsAg和HBV DNA水平呈负相关。通过多变量回归揭示HBV基因型和BCP突变的存在与HBeAg阴性状态和增加的氨基酸非共有性之间的关联无关。

最初，92名慢性乙型肝炎患者接受48周治疗，每周一次皮下注射聚乙二醇干扰素α-2a180μg，每日服用阿德福韦酯10 mg。其中84人完成了治疗和2年的随访。

在治疗后随访的第72周，评估参与者的组合反应的实现，其包括HBV DNA水平≤2000IL/ mL，HBeAg阴性状态和丙氨酸氨基转移酶的持续正常水平。序列和谐用于识别HBeAg状态亚组之间以及对治疗有反应和无应答的亚组之间的共同位点。


该研究的研究人员得出结论：“序列和谐鉴定了许多与HBeAg状态相关的氨基酸变化以及对聚乙二醇干扰素/阿德福韦联合治疗的反应。”

披露：本研究由荷兰罗氏公司资助。
参考

van der Ree MH，Jansen L，Welkers MRA，Reesink HW，Feenstra KA，Kootstra NA。深度测序确定了慢性乙型肝炎患者的乙型肝炎病毒核心蛋白特征[在线发表于2018年8月16日]。抗病毒药物doi：10.1016 / j.antiviral.2018.08.009