TY - JOUR
T1 - Hepatitis B surface antigen
T2 - Relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B
AU - Manesis, Emanuel K.
AU - Papatheodoridis, George V.
AU - Tiniakos, Dina G.
AU - Hadziyannis, Emilia S.
AU - Agelopoulou, Olga P.
AU - Syminelaki, Thalia
AU - Papaioannou, Christos
AU - Nastos, Theodoros
AU - Karayiannis, Peter
PY - 2011/7
Y1 - 2011/7
N2 - 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/mm2 (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.
AB - 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/mm2 (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.
KW - cccDNA
KW - HBcAg-immunostaining
KW - HBeAg-negative chronic hepatitis B
KW - HBsAg-immunostaining
KW - Serum HBsAg levels
KW - Serum HBV DNA
KW - Total liver HBV DNA
UR - http://www.scopus.com/inward/record.url?scp=79958800541&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2010.10.027
DO - 10.1016/j.jhep.2010.10.027
M3 - Article
C2 - 21145875
AN - SCOPUS:79958800541
SN - 0168-8278
VL - 55
SP - 61
EP - 68
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 1
ER -