Kinetics of hepatitis B surface antigen decline during 3 years of telbivudine treatment in hepatitis B e antigen-positive patients
Karsten Wursthorn1,*, Mechthild Jung2, Antonio Riva3, Zachary D. Goodman4, Patricia Lopez2, Weibin Bao5, Michael P. Manns1, Heiner Wedemeyer1,*,?? , Nikolai V. Naoumov2DOI: 10.1002/hep.23905
Hepatology
Accepted Article (Accepted, unedited articles published online for future issues)
Abstract
The impact of prolonged direct antiviral therapy on hepatitis B surface antigen (HBsAg) levels in patients with chronic hepatitis B (CHB) is poorly understood. We quantitatively assessed serum HBsAg levels during 3 years of telbivudine treatment and their relationship with virologic and biochemical characteristics in 162 hepatitis B e antigen–positive patients who maintained undetectable serum HBV DNA long-term. Telbivudine treatment progressively reduced serum HBsAg levels (mean ± standard deviation) from baseline (3.8 ± 0.6 log10 IU/mL) to treatment week 24 (3.4 ± 0.7 log10 IU/mL); year 1 (3.3 ± 0.8 log10 IU/mL); and year 3 (3.0 ± 1.4 log10 IU/mL; all P <0.0001). In this patient population, HBsAg loss was observed in 9 (6%) of 162 patients through year 3. During the first year of treatment, 3 patterns of HBsAg decline were observed: rapid (≥1 log10 IU/mL) in 32 patients; slow (0 to 1 log10 IU/mL) in 74 patients, and steady levels in 56 patients. These 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 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. (HEPATOLOGY 2010.)