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

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 longitudi...

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Autores principales:	Mary C. Kuhns, Vera Holzmayer, Anne L. McNamara, Mark Anderson, Gavin A. Cloherty
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Hepatitis B virus Acute HBV Seroconversion Immunoassays Biomarkers HBsAg Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/2e26a07ed5a14040b1368323428e032b
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spelling	oai:doaj.org-article:2e26a07ed5a14040b1368323428e032b2021-12-05T12:03:03ZHepatitis B seroconversion revisited: new insights into the natural history of acute hepatitis B virus (HBV) infection from quantitative and highly sensitive assays and novel biomarkers10.1186/s12985-021-01706-w1743-422Xhttps://doaj.org/article/2e26a07ed5a14040b1368323428e032b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12985-021-01706-whttps://doaj.org/toc/1743-422XAbstract 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 × 105–2.7 × 109 IU/ml for HBV DNA and 7.9–1.1 × 105 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 × 103 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 × 105 to > 6.4 × 106 U/ml and correlated with HBeAg values (R2 = 0.9495) and with HBV DNA values (R2 = 0.8828). Peak pgRNA values ranged from 1.6 × 103 to 1.4 × 108 U/ml and correlated with HBV DNA (R2 = 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.Mary C. KuhnsVera HolzmayerAnne L. McNamaraMark AndersonGavin A. ClohertyBMCarticleHepatitis B virusAcute HBVSeroconversionImmunoassaysBiomarkersHBsAgInfectious and parasitic diseasesRC109-216ENVirology Journal, Vol 18, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatitis B virus Acute HBV Seroconversion Immunoassays Biomarkers HBsAg Infectious and parasitic diseases RC109-216
spellingShingle	Hepatitis B virus Acute HBV Seroconversion Immunoassays Biomarkers HBsAg Infectious and parasitic diseases RC109-216 Mary C. Kuhns Vera Holzmayer Anne L. McNamara Mark Anderson Gavin A. Cloherty 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
description	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 × 105–2.7 × 109 IU/ml for HBV DNA and 7.9–1.1 × 105 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 × 103 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 × 105 to > 6.4 × 106 U/ml and correlated with HBeAg values (R2 = 0.9495) and with HBV DNA values (R2 = 0.8828). Peak pgRNA values ranged from 1.6 × 103 to 1.4 × 108 U/ml and correlated with HBV DNA (R2 = 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.
format	article
author	Mary C. Kuhns Vera Holzmayer Anne L. McNamara Mark Anderson Gavin A. Cloherty
author_facet	Mary C. Kuhns Vera Holzmayer Anne L. McNamara Mark Anderson Gavin A. Cloherty
author_sort	Mary C. Kuhns
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2e26a07ed5a14040b1368323428e032b
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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

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