title: Reduction of hepatitis B surface antigen and covalently closed circular DNA by nucleos(t)ide analogues of different potency.
abstract: OBJECTIVE
  Few studies have investigated the effects of different nucleos(t)ide analogues against hepatitis B virus (HBV) on levels of covalently closed circular DNA (cccDNA) and hepatitis B surface antigen (HBsAg) in patients. We measured the magnitude of reduction of cccDNA and HBsAg by nucleos(t)ide analogue therapy and assessed the correlation between their reductions.
  
  
  METHODS
  We recruited 124 patients who were treated with 1 of the 5 nucleos(t)ide analogues (lamivudine, adefovir, entecavir, telbivudine, or clevudine). All patients had undergone liver biopsy when treatment began (baseline) and 1 year later. The cccDNA and HBsAg levels were measured by real-time polymerase chain reaction and the Elecsys II HBsAg Assay, respectively.
  
  
  RESULTS
  After 1 year of treatment, HBV in 7 patients had become resistant to the nucleos(t)ide analogue. The remaining 117 patients had an average reduction of approximately 0.2 log10 IU/mL in HBsAg, 5 log10 IU/mL in serum level of HBV DNA, 2 log10 copies/cell in intrahepatic total HBV DNA, and 1 log10 copies/cell in cccDNA. Although 88 of 117 patients (75%) had undetectable serum levels of HBV DNA (<12 IU/mL), all had detectable levels of HBsAg, and only 5 (4%) had undetectable levels of cccDNA. On treatment with nucleos(t)ide analogues, patients with greater reductions in levels of cccDNA had greater reductions in HBsAg, but these reductions did not reach statistically significant correlations.
  
  
  CONCLUSIONS
  Although nucleos(t)ide analogues potently reduced serum levels of HBV DNA, the reduction of HBsAg and cccDNA was small. In short-term therapy, the magnitude of HBsAg reduction does not correlate with that of cccDNA reduction.
authors: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China.
authors: Danny Ka-Ho
authors: DK
authors: Wong
authors: Wai-Kay
authors: WK
authors: Seto
authors: James
authors: J
authors: Fung
authors: Philip
authors: P
authors: Ip
authors: Fung-Yu
authors: FY
authors: Huang
authors: Ching-Lung
authors: CL
authors: Lai
authors: Man-Fung
authors: MF
authors: Yuen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D001706:Biopsy; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000032:analysis*; D006801:Humans; D007118:Immunoassay; D008099:Liver / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000008:administration & dosage*; D009711:Nucleotides / Q000008:administration & dosage*; D016133:Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D004270:DNA, Circular; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D009705:Nucleosides; D009711:Nucleotides
keywords: Antiviral Therapy; CHB; HBV; HBeAg; NA; Prognosis; Response to Therapy; Viral Hepatitis; cccDNA; chronic hepatitis B; covalently closed circular DNA; hepatitis B e antigen; hepatitis B virus; nucleos(t)ide analogue; qHBsAg; quantitative hepatitis B surface antigen