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

Abstract

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.

Combination Therapy with Antiviral Drugs and Hepatitis B Vaccine in Incidentally-Detected and Asymptomatic Chronic Hepatitis Virus B Carriers at Bangladesh

“…The extent of liver damage was also decreased in patients receiving the combination therapy. This is not the first study of combination therapy in patients with chronic HBV infection, but most of these clinical trials were carried out in patients in the immune clearance phase of chronic HBV infection (4,5). In addition, most of the published clinical trials were conducted in developed countries with advanced facilities.…”

Research progress of therapeutic vaccines for treating chronic hepatitis B

“…Though this new combination therapy was safe, there was no significant difference in HBeAg seroconversion and HBeAg loss among these groups. 31 In a phase III trial, 195 CHB patients received either 12 injections of HB-AS02V (HBsAg/AS02B adjuvant) C LAM daily, or LAM only within 52 weeks. Both combination therapy and control group was safe and well tolerated, however, there was no significant difference between them.…”

Immune therapy for hepatitis B

“…The nature of antigen and adjuvants, dose of vaccine, and duration of therapy underwent considerable alterations during the last 18 years. Wen and her group used an antigen-antibody complex vaccine containing HBsAg and anti-HBs as a therapeutic vaccine (67), whereas others used a HBsAg-based vaccine with antiviral agents or other immune modulators to increase the therapeutic potential of these vaccines (68)(69)(70)(71)(72). Also, a DNA-based vaccine expressing HBsAg was used in CHB patients (73).…”