Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside/nucleotide analogue therapy: finite treatment duration unlikely

J Hepatol. 2013 Apr;58(4):676-83. doi: 10.1016/j.jhep.2012.11.039. Epub 2012 Dec 3.


Background & aims: Information regarding long-term HBsAg kinetics during treatment with nucleoside/nucleotide analogues is limited. The aim of the present study was to assess whether finite nucleoside/nucleotide analogue treatment duration could be envisaged during the patient's lifetime.

Methods: Patients with chronic hepatitis B receiving different schedules of nucleoside/nucleotide analogues were followed for a median duration of 102 months, i.e., 8.5 years (interquartile range: 88-119 months). Long-term HBV DNA and HBsAg level kinetics were modeled in order to estimate time to clear HBsAg during therapy in patients with undetectable HBV DNA.

Results: Antiviral therapy was associated with a slow but consistent reduction in the level of HBsAg in most of the patients. Three patterns of HBsAg level declines were identified: decline during both the detectable and undetectable HBV DNA phases; decline during the HBV DNA detectable period only; decline during the HBV DNA undetectable period only. The mean HBsAg titer at the time when HBV DNA became undetectable was 3.29 ± 0.49 Log₁₀ international units (IU)/ml, and the mean slope was -0.007 ± 0.007 Log₁₀ IU/month, i.e., an average decline of 0.084 Log₁₀ IU/year. The corresponding calculated median number of years needed to clear HBsAg was 52.2 years (interquartile range: 30.8-142.7).

Conclusions: This study, based on the very long-term follow-up of patients with chronic hepatitis B treated with potent nucleoside/nucleotide analogues, shows that HBsAg clearance is unlikely to occur during the patient's lifetime, even if HBV replication is well controlled. Thus, lifetime therapy is required in the vast majority of HBV-infected patients.

MeSH terms

  • Adenine / administration & dosage
  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Drug Resistance, Viral
  • Female
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B virus / drug effects
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology*
  • Humans
  • Kinetics
  • Lamivudine / administration & dosage
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Nucleosides / therapeutic use
  • Nucleotides / therapeutic use
  • Organophosphonates / administration & dosage
  • Tenofovir


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Nucleosides
  • Nucleotides
  • Organophosphonates
  • Lamivudine
  • entecavir
  • Guanine
  • adefovir
  • Tenofovir
  • Adenine