Kinetics of Hepatitis B Surface Antigen Decline During 3... : Hepatology (original) (raw)

Viral Hepatitis

Kinetics of Hepatitis B Surface Antigen Decline During 3 Years of Telbivudine Treatment in Hepatitis B e Antigen–Positive Patients

Wursthorn, Karsten1,*; Jung, Mechthild2; Riva, Antonio3; Goodman, Zachary D.4; Lopez, Patricia2; Bao, Weibin5; Manns, Michael P.1; Wedemeyer, Heiner1,*; Naoumov, Nikolai V.2

1_Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany_

2_Novartis Pharma AG, Basel, Switzerland_

3_Institute of Hepatology, University College, London, UK_

4_American International Pathology Laboratories, Silver Spring, MD_

5_Novartis Pharmaceuticals Corporation, East Hanover, NJ_

*Address reprint requests to: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. E-mail:[email protected]or[email protected]; fax: (49)-511-532-4896.

Received 21 February 2010; accepted 30 July 2010

K. W., H. W., and M. P. Manns received grant support from Novartis Pharma AG, Basel, Switzerland.

View this article online atwileyonlinelibrary.com.

Potential conflict of interest: Dr. Wedemeyer is a consultant for Novartis. Dr. Manns is a consultant for Novartis, Roche, and Gilead.

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. (Hepatology 2010