Kinetics of Hepatitis B Surface Antigen Decline During 3 Years of Telbivudine Treatment in Hepatitis B E Antigen-Positive Patients

Hepatology. 2010 Nov;52(5):1611-20. doi: 10.1002/hep.23905.

Abstract

The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment, as well as their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen-positive patients who maintained undetectable serum hepatitis B virus (HBV) DNA long-term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± SD) from baseline (3.8 ± 0.6 log₁₀ IU/mL) to treatment week 24 (3.4 ± 0.7 log₁₀ IU/mL), treatment year 1 (3.3 ± 0.8 log₁₀ IU/mL), and treatment year 3 (3.0 ± 1.4 log₁₀ IU/mL) (P <0.0001). In this patient population, HBsAg loss was observed in nine (6%) of 162 patients through year 3. During the first year of treatment, three patterns of HBsAg decline were observed: rapid (≥ 1 log₁₀ IU/mL) in 32 patients, slow (0-1 log₁₀ IU/mL) in 74 patients, and steady levels in 56 patients. These findings were associated with different likelihoods of HBsAg loss during long-term telbivudine therapy. Eight of 32 patients with rapid HBsAg decline versus none of 56 patients with steady HBsAg levels achieved HBsAg loss at year 3 (P = 0.0024). HBV genotype was a significant determinant for HBsAg kinetics, with the fastest decline in genotype A patients. In patients with subsequent HBsAg loss, viral antigens were already undetectable in liver biopsy samples after 1 year of treatment. This was associated with markedly enhanced antiviral T cell reactivity.

Conclusion: In patients who have effective suppression of viral replication during telbivudine treatment, a rapid decline in serum HBsAg levels during the first year may identify those with a greater likelihood of achieving HBsAg clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Body Weight
  • Continental Population Groups
  • Enzyme-Linked Immunosorbent Assay
  • Genotype
  • Hepatitis B Core Antigens / metabolism
  • Hepatitis B Surface Antigens / blood*
  • Hepatitis B Surface Antigens / metabolism
  • Hepatitis B e Antigens / analysis*
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Kinetics
  • Liver / metabolism
  • Liver / virology
  • Lymphocyte Activation
  • Nucleosides / therapeutic use*
  • Patient Selection
  • Pyrimidinones / therapeutic use*
  • T-Lymphocytes / immunology
  • Telbivudine
  • Thymidine / analogs & derivatives
  • Time Factors

Substances

  • Antiviral Agents
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Nucleosides
  • Pyrimidinones
  • Telbivudine
  • Thymidine