Background & Aims: Translation of HBsAg depends on transcription of the
appropriate mRNAs from cccDNA, but its relation to other hepatitis B
virus (HBV) replication parameters is not known, inasmuch as integrated
sequences of HBV-DNA may also contribute to its serum levels, especially
in HBeAg-negative chronic hepatitis B (CHB) patients.
Methods: We investigated HBsAg serum levels, its hepatocellular
expression, and their relationship to HBV replicative- and host-response
parameters before treatment in 54 HBeAg-negative CHB patients and in 15
of them after 40.1 +/- 33.3 months of virological response on oral
antiviral (NUC) therapy also. Liver cccDNA and HBV-DNA quantitation,
HBsAg- and HBcAg-immunostaining were performed in the same needle biopsy
material, while serum HBsAg and HBV-DNA levels were measured in samples
drawn on the day of liver biopsy.
Results: In untreated patients, serum HBsAg correlated positively with
HBsAg-positive hepatocytes/mm(2) (p = 0.003) and weakly with serum
HBV-DNA, but not with cccDNA, liver HBV-DNA, HBcAg-positive
hepatocytes/mm(2), or ALT. cccDNA correlated significantly with liver
HBV-DNA (p <0.00001), ALT (p = 0.001), and serum HBV-DNA levels (p =
0.012) but not with liver HBsAg or HBcAg. Antiviral therapy decreased
serum HBsAg levels by 79.6% (p = 0.012) and liver HBV-DNA by 84.4% (p
= 0.026) in paired comparisons and, as expected, significantly decreased
serum HBV-DNA and ALT levels, but not cccDNA.
Conclusions: In untreated HBeAg-negative CHB, serum HBsAg levels reflect
liver HBsAg, but not cccDNA or liver HBV-DNA, suggesting that they are
not solely dependent on the replicative cycle of HBV. Effective NUC
therapy for 3.34 years significantly lowers serum HBsAg and liver
HBV-DNA, but not cccDNA. (C) 2010 European Association for the Study of
the Liver. Published by Elsevier B.V. All rights reserved
