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study on 3-6.6 years of nucs response and hbsag/cccdna response
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±33.3months 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/mm2 (p=0.003) and weakly with serum HBV-DNA, but not with cccDNA, liver HBV-DNA, HBcAg-positive hepatocytes/mm2, 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 3.34years significantly lowers serum HBsAg and liver HBV-DNA, but not cccDNA.
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titles study on journal of hepatology
Hepatitis B surface antigen: Relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B

Emanuel K. Manesis, George V. Papatheodoridis, Dina G. Tiniakos, Emilia S. Hadziyannis, Olga P. Agelopoulou, Thalia Syminelaki, Christos Papaioannou, Theodoros Nastos, Peter Karayiannis
Received 1 June 2010; received in revised form 30 September 2010; accepted 6 October 2010. published online 09 December 2010.
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it would be very good to find full access to this study because very very well done, i think this is the first study i see done correctly with biopsy measure of cccdna, hbcag and so on for such a long time

it is very interesting because with 80% hbsag reduction we are in the range of about 1000iu/ml (hbeag neg has hbsag mainly aournd 5000iu/ml baseline) and we do know that interferon add on have sure results with such low levels
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I have a hard copy of the paper, but I can't find the file. I had a hard time arguing with someone in the Chinese forum who took the view, from the paper, that there is no relationship between serum HbsAg quantity and cccDNA.

Manesis's email address:
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relationship is between total transcription activity of cccdna and hbsag and not cccdna quantity.but anyway it doesn t matter we know that serum hbsag correlates with immune response and hbv immune control and that's all we care for
we actually dont care about cccdna which can be present even after hbsag negative and hbsab positive......cccdna will be cleared slowly by hbv immune control gained after hbsag neg and hbsab pos
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