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Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers
Author(s) -
Thompson Alexander J.V.,
Nguyen Tin,
Iser David,
Ayres Anna,
Jackson Kathy,
Littlejohn Margaret,
Slavin John,
Bowden Scott,
Gane Edward J.,
Abbott William,
Lau George K.K.,
Lewin Sharon R.,
Visvanathan Kumar,
Desmond Paul V.,
Locarnini Stephen A.
Publication year - 2010
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23571
Subject(s) - cccdna , hbsag , hbeag , hepatitis b virus , virology , titer , viral load , hepatitis b , viral replication , medicine , antigen , virus , biology , immunology
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‐naïve 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. (H EPATOLOGY 2010)