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Antimicrobial Agents and Chemotherapy, December 2009, p. 5134-5140, Vol. 53, No. 12
0066-4804/09/$08.00+0 doi:10.1128/AAC.00276-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
Randomized Controlled Study Investigating Viral Suppression and Serological Response following Pre-S1/Pre-S2/S Vaccine Therapy Combined with Lamivudine Treatment in HBeAg-Positive Patients with Chronic Hepatitis B
Pham Thi Le Hoa,1,2*
Nguyen Tien Huy,3
Le The Thu,4
Cao Ngoc Nga,1,2
Kazuhiko Nakao,5
Katsumi Eguchi,5
Nguyen Huu Chi,1,2
Bui Huu Hoang,6 and
Kenji Hirayama3,7,8*
Department of Infectious Diseases,1 Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City,6 The Hospital for Tropical Diseases, Ho Chi Minh City,2 University of Medicine at Can Tho City, Can Tho City, Vietnam,4 Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN),3 Department of Internal Medicine,5 Center for International Collaborative Research, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523,7 Global COE Program, Nagasaki University, Nagasaki, Japan8
Received 28 February 2009/ Returned for modification 19 May 2009/ Accepted 10 September 2009
The aim of the current study was to evaluate viral suppression following combined treatment with an S/pre-S1/pre-S2 vaccine and lamivudine in patients with chronic hepatitis B. We established a randomized, controlled clinical trial to compare the responses of three different treatment groups: those receiving vaccine monotherapy, lamivudine monotherapy, or combination treatment. Viral response was evaluated via hepatitis B virus (HBV) DNA suppression using different levels of classification. Seroconversion was evaluated via HBeAg loss, HBeAg seroconversion, HBsAg loss, and anti-HBs response. We found that the group receiving combination treatment demonstrated a significant increase in viral suppression over that for the lamivudine or vaccine monotherapy group, although the HBeAg seroconversion rate was not different. This enhanced suppression effect in the combination group was reversed after the discontinuation of vaccine treatment, suggesting that booster doses are required for a sustained viral response. Anti-HBs was detected in 55/120 vaccine recipients, but only 3 patients demonstrated HBsAg loss, indicating that the vaccine-induced anti-HBs was unable to completely neutralize HBsAg in the serum. At the study end point, anti-HBs responders showed significantly higher HBeAg seroconversion rates, greater suppression of HBV DNA levels, and a lower median reduction in HBV DNA levels than those of anti-HBs nonresponders. Our results suggest that combined treatment with the vaccine and lamivudine was significantly more effective than lamivudine monotherapy in the short term and was especially successful in producing viral suppression and an enhanced anti-HBs antibody response.
* Corresponding author. Mailing address for Pham Thi Le Hoa: Department of Infectious Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, 217 Hong Bang, District 5, Ho Chi Minh City, Vietnam. Phone: 84838558411. Fax: 84838552304. E-mail: hoaph{at}hcm.vnn.vn. Mailing address for Kenji Hirayama: Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan. Phone: 81958197805. Fax: 81958197821. E-mail: hiraken{at}nagasaki-u.ac.jp
Published ahead of print on 21 September 2009.
Antimicrobial Agents and Chemotherapy, December 2009, p. 5134-5140, Vol. 53, No. 12
0066-4804/09/$08.00+0 doi:10.1128/AAC.00276-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.
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