Abstract
BackgroundHepatitis 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.Methods137 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).ResultsPeak 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).ConclusionTraditional 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.
Highlights
Viral hepatitis continues to account for significant global disease and high mortality from liver cancer and cirrhosis
The order of appearance of serum Hepatitis B virus (HBV) markers follows a consistent pattern with an eclipse phase preceding the release of virions into the blood, followed by the first detectable levels of HBV Hepatitis B virus DNA (DNA), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and antibodies to HBV core and HBeAg antigens
We report detailed serological and molecular data on the course of hepatitis B seroconversion using state of the art assays for quantitation of HBsAg and HBeAg, a new highly sensitive HBsAg assay, and novel biomarkers for quantitation of HBV pregenomic RNA and HBV core related antigen (HBcrAg)
Summary
Viral hepatitis continues to account for significant global disease and high mortality from liver cancer and cirrhosis. The course of HBV serum markers during a typical acute self-limited HBV infection is usually depicted as a composite of traditional HBV marker data from studies of blood donors [2,3,4]. The order of appearance of serum HBV markers follows a consistent pattern with an eclipse phase preceding the release of virions into the blood, followed by the first detectable levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and antibodies to HBV core and HBeAg antigens (anti-HBc IgM, total anti-HBc, and antiHBe). Hepatitis B virus (HBV) serum markers during typical acute self-limited infection are usually depicted as a composite of traditional HBV markers.
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