Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers

Alex Thompson, Tin Nguyen, David Iser, Anna Ayres, Kathy Jackson, Margaret Littlejohn, John Slavin, Scott Bowden, Edward Gane, William Abbott, George Lau, Sharon Lewin, Kumar Visvanathan, Paul Desmond, Stephen Locarnini

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Abstract

Although threshold levels for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) titers have recently been proposed to guide therapy for chronic hepatitis B (CHB), their relationship to circulating hepatitis B virus (HBV) DNA and intrahepatic HBV replicative intermediates, and the significance of emerging viral variants, remains unclear. We therefore tested the hypothesis that HBsAg and HBeAg titers may vary independently of viral replication in vivo. In all, 149 treatment-na??ve CHB patients were recruited (HBeAg-positive, n = 71; HBeAg-negative, n = 78). Quantification of HBeAg and HBsAg was performed by enzyme immunoassay. Virological characterization included serum HBV DNA load, HBV genotype, basal core promoter (BCP)/precore (PC) sequence, and, in a subset (n = 44), measurement of intrahepatic covalently closed circular DNA (cccDNA) and total HBV DNA, as well as quantitative immunohistochemical (IHC) staining for HBsAg. In HBeAg-positive CHB, HBsAg was positively correlated with serum HBV DNA and intrahepatic cccDNA and total HBV DNA (r = 0.69, 0.71, 0.76, P <0.01). HBeAg correlated with serum HBV DNA (r = 0.60, P <0.0001), although emerging BCP/PC variants reduced HBeAg titer independent of viral replication. In HBeAg-negative CHB, HBsAg correlated poorly with serum HBV DNA (r = 0.28, P = 0.01) and did not correlate with intrahepatic cccDNA nor total HBV DNA. Quantitative IHC for hepatocyte HBsAg confirmed a relationship with viral replication only in HBeAg-positive patients. CONCLUSION: The correlation between quantitative HBsAg titer and serum and intrahepatic markers of HBV replication differs between patients with HBeAg-positive and HBeAg-negative CHB. HBeAg titers may fall independent of viral replication as HBeAg-defective variants emerge prior to HBeAg seroconversion. These findings provide new insights into viral pathogenesis and have practical implications for the use of quantitative serology as a clinical biomarker.
Original languageEnglish
Pages (from-to)1933 - 1944
Number of pages12
JournalHepatology
Volume51
Issue number6
DOIs
Publication statusPublished - 2010

Cite this

Thompson, A., Nguyen, T., Iser, D., Ayres, A., Jackson, K., Littlejohn, M., Slavin, J., Bowden, S., Gane, E., Abbott, W., Lau, G., Lewin, S., Visvanathan, K., Desmond, P., & Locarnini, S. (2010). Serum hepatitis B surface antigen and hepatitis B e antigen titers: disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers. Hepatology, 51(6), 1933 - 1944. https://doi.org/10.1002/hep.23571