Aims: The aim was to test the efficacy of a pre-S2-containing vaccine (Genhevac-B) in chronic hepatitis B (CHB). Twenty-five naive patients (22 male, three female; median age 35; range: 6-69 years) with CHB were recruited. The inclusion criteria were: hepatitis B e antigen (HBeAg) positive or HBV-DNA detectable with liquid hybridization; alanine aminotransferase (ALT) is at least 1.5-fold the upper normal limit and histological evidence of chronic hepatitis.
Methods: In the first period, all patients received monthly injections of 20, 40 and 60 microg of the vaccine. One month after the last injection, patients who still had HBV-DNA were divided into two randomly assigned groups. While the patients in the first group and the patients who lost HBV-DNA in the first period continued to receive monthly injections of 20 microg vaccine for a further 6 months, the patients in the second group received 9 MU interferon alpha-2b (Roferon-A), three times per week using the same method as for the first group. Patients were followed up after 12 months without treatment. Response was defined as the loss of HBV-DNA and normalization of ALT.
Results: Six of the 25 patients lost HBV-DNA after 3 months. Nine of the remainder were randomly placed in the first group (vaccine-only) and 10 were placed in the second group (vaccine + interferon). End-of-treatment response was achieved, overall, 8/15 from the vaccine group and 6/10 from the combination. One patient from each group relapsed during the follow up. Overall, the sustained response (SR) rate was 46% (7/15) in the vaccine group, and 50% (5/10) in the combination group. Histological improvement was achieved in 6/7 SR with vaccine-only and all five with combination treatment, while 1/8 of failures of vaccine and 2/5 of failures of combination improved.
Conclusions: It was concluded that Genhevac-B decreases serum HBV-DNA levels in the majority of patients with CHB and sustained clearance was achieved in some patients. Combination of interferon-alpha with Genhevac-B is effective for the vaccine failures and may increase sustained response compared to interferon-alpha alone. However, the mechanism of action is yet to be explained.