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乙型肝炎血清学转换再探讨:从定量和高灵敏度检测方法及新型生物标志物看乙型肝炎病毒(HBV)感染的自然史。

Hepatitis B seroconversion revisited: new insights into the natural history of acute hepatitis B virus (HBV) infection from quantitative and highly sensitive assays and novel biomarkers.

机构信息

Infectious Diseases Research, Diagnostics Division, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL, 60064, USA.

出版信息

Virol J. 2021 Nov 29;18(1):235. doi: 10.1186/s12985-021-01706-w.

DOI:10.1186/s12985-021-01706-w
PMID:34844619
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8628455/
Abstract

BACKGROUND

Hepatitis B virus (HBV) serum markers during typical acute self-limited infection are usually depicted as a composite of traditional HBV markers. The current study updates and expands our knowledge of acute hepatitis B with quantitative molecular and serological data on longitudinal samples from five plasmapheresis donors with acute HBV.

METHODS

137 longitudinal samples from five plasmapheresis donors with acute HBV were tested, four with self-limited infection and one who developed persistent infection. Testing included quantitative hepatitis B surface antigen (HBsAg), antibodies to HBV antigens, quantitative HBV e antigen (HBeAg), HBV DNA, quantitative HBV core-related antigen (HBcrAg), the highly sensitive ARCHITECT HBsAg NEXT (HBsAgNx) assay, and a quantitative research assay for HBV pregenomic RNA (pg RNA).

RESULTS

Peak levels of HBV DNA and HBsAg differed by several orders of magnitude among the panels (2.2 × 10-2.7 × 10 IU/ml for HBV DNA and 7.9-1.1 × 10 IU/ml for HBsAg). HBsAg levels peaked an average of 2.8 days after the HBV DNA peak. The overall duration of observed HBsAg positivity was increased by the more sensitive HBsAgNx assay compared to the quantitative assay in four panels. Intermittently detectable low-level HBV DNA was observed after HBsAg loss in three panels. Peak HBeAg levels occurred 2-20 days after the DNA peak and ranged from 1.1 to 4.5 × 10 IU/ml. In four panels with resolution of infection, anti-HBs levels indicating immunity (≥ 10 mIU/ml) were detected 19-317 days after the HBV DNA peak. Maximum HBcrAg concentrations ranged from 1 × 10 to > 6.4 × 10 U/ml and correlated with HBeAg values (R = 0.9495) and with HBV DNA values (R = 0.8828). Peak pgRNA values ranged from 1.6 × 10 to 1.4 × 10 U/ml and correlated with HBV DNA (R = 0.9013).

CONCLUSION

Traditional and new/novel HBV biomarkers were used to generate molecular and serological profiles for seroconversion panels spanning the early to late phases of acute HBV. Seroconversion profiles were heterogeneous and may be instructive in appreciating the spectrum of acute profiles relative to the typical composite representation.

摘要

背景

在典型的急性自限性感染中,乙型肝炎病毒 (HBV) 血清标志物通常表现为传统 HBV 标志物的组合。本研究通过对 5 名接受血浆置换的急性 HBV 患者的纵向样本进行定量分子和血清学检测,更新和扩展了我们对急性乙型肝炎的认识。

方法

对 5 名急性 HBV 血浆置换供体的 137 个纵向样本进行检测,其中 4 名患者为自限性感染,1 名患者发展为持续性感染。检测包括定量乙型肝炎表面抗原 (HBsAg)、HBV 抗原抗体、定量 HBeAg、HBV DNA、定量 HBV 核心相关抗原 (HBcrAg)、高灵敏度 ARCHITECT HBsAg NEXT (HBsAgNx) 检测以及 HBV 前基因组 RNA (pgRNA) 的定量研究检测。

结果

HBV DNA 和 HBsAg 的峰值水平在不同组别之间相差几个数量级(HBV DNA 为 2.2×10-2.7×10 IU/ml,HBsAg 为 7.9-1.1×10 IU/ml)。HBsAg 水平在 HBV DNA 峰值后平均 2.8 天达到峰值。与四个组别的定量检测相比,更敏感的 HBsAgNx 检测增加了观察到的 HBsAg 阳性的总持续时间。在三个组中,HBsAg 丢失后观察到间歇性低水平 HBV DNA。HBeAg 水平峰值出现在 DNA 峰值后 2-20 天,范围为 1.1-4.5×10 IU/ml。在四个感染得到解决的组中,在 HBV DNA 峰值后 19-317 天检测到表明免疫(≥10 mIU/ml)的抗-HBs 水平。最大 HBcrAg 浓度范围为 1×10-6.4×10 U/ml,与 HBeAg 值(R=0.9495)和 HBV DNA 值(R=0.8828)相关。峰值 pgRNA 值范围为 1.6×10-1.4×10 U/ml,与 HBV DNA 相关(R=0.9013)。

结论

传统和新型/新型 HBV 生物标志物用于生成跨越急性 HBV 早期到晚期的血清转换组的分子和血清学谱。血清转换谱具有异质性,在理解急性谱相对于典型组合表现的范围方面可能具有指导意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/8628455/6afeddb08e05/12985_2021_1706_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/8628455/4fb35ad8ed34/12985_2021_1706_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/8628455/6afeddb08e05/12985_2021_1706_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/8628455/4fb35ad8ed34/12985_2021_1706_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fdb3/8628455/6afeddb08e05/12985_2021_1706_Fig2_HTML.jpg

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