Reduction of hepatitis B surface antigen and covalently closed circular DNA by nucleos(t)ide analogues of different potency

Clin Gastroenterol Hepatol. 2013 Aug;11(8):1004-10.e1. doi: 10.1016/j.cgh.2013.01.026. Epub 2013 Feb 1.


Background & aims: 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.

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.

MeSH terms

  • Adult
  • Antiviral Agents / administration & dosage*
  • Biopsy
  • DNA, Circular / analysis
  • DNA, Viral / analysis*
  • Female
  • Hepatitis B / drug therapy*
  • Hepatitis B Surface Antigens / analysis*
  • Humans
  • Immunoassay
  • Liver / virology*
  • Male
  • Middle Aged
  • Nucleosides / administration & dosage*
  • Nucleotides / administration & dosage*
  • Polymerase Chain Reaction
  • Treatment Outcome


  • Antiviral Agents
  • DNA, Circular
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Nucleosides
  • Nucleotides