title: Hepatitis B surface antigen: relation to hepatitis B replication parameters in HBeAg-negative chronic hepatitis B.
abstract: OBJECTIVE
  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/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.
authors.affiliation: Division of Internal Medicine, Athens University Medical School, Athens, Greece. emanesis@med.uoa.gr
authors.forename: Emanuel K
authors.initials: EK
authors.lastname: Manesis
authors.forename: George V
authors.initials: GV
authors.lastname: Papatheodoridis
authors.forename: Dina G
authors.initials: DG
authors.lastname: Tiniakos
authors.forename: Emilia S
authors.initials: ES
authors.lastname: Hadziyannis
authors.forename: Olga P
authors.initials: OP
authors.lastname: Agelopoulou
authors.forename: Thalia
authors.initials: T
authors.lastname: Syminelaki
authors.forename: Christos
authors.initials: C
authors.lastname: Papaioannou
authors.forename: Theodoros
authors.initials: T
authors.lastname: Nastos
authors.forename: Peter
authors.initials: P
authors.lastname: Karayiannis
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage; D001483:Base Sequence; D004270:DNA, Circular / Q000097:blood / Q000235:genetics; D004279:DNA, Viral / Q000097:blood / Q000235:genetics; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000821:virology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008099:Liver / Q000821:virology; D008297:Male; D008875:Middle Aged; D014766:Viremia / Q000188:drug therapy / Q000821:virology; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens