IMMUNOTHERAPY OF CHRONIC HEPATITIS-B BY ANTI HBV VACCINE

Vaccine therapy is now used in various infectious diseases. The hepati tis B virus (HBV) leads to chronic infection in around 5% of patients with a high risk of chronic active hepatitis which may result in cirrh osis and hepatocellular carcinoma. The partial efficacy of antiviral t herapies (40% of sustained inhibition of HBV replication), their cost, their possible side effects and the immune-mediated pathology of HBV infection explain the need of new immune therapies in treating HBV inf ection. Experiment al and clinical evidences suggest the usefulness of vaccine therapy in HBV chronic infection. In a pilot and opened study , forty-ah consecutive chronic HBsAg carriers with chronic hepatitis a nd detectable serum HBV DNA were given 3 standard injections of the Ge nHevac B(R) vaccine at one month interval. Six months after the first injection, 12 patients (26.1%) had undetectable HBV DNA while 8 others showed significant decrease (more than 50%) in HBV DNA titers. Six of these 12 responders received a standard course of alpha-Interferon (5 MU thrice weekly subcutaneously for 4 months) and all six had still u ndetectable HBV replication at the end of follow-up, hmong the 34 non responders to vaccine, 20 were given alpha-interferon and 2 the monoph osphate derivate of Vidarabine: 12 of these 22 patients stopped HBV re plication and in all 12, vaccine therapy had induced a significant dec rease of HBV replication before the antiviral treatment with a decreas e of mean serum HBV DNA from 392 pg/ml before to 217 pg/ml after vacci ne therapy. In an ongoing controlled study, using the same vaccine sch edule, serum HBV DNA disappeared more frequently after 6 months, in pa tients who were given a preS2/S vaccine (7/35) than in patients who re ceived a S vaccine (1/21) or no vaccine (1/32). In responders to vacci ne, an induction of specific proliferative responses was observed and this may contribute to the potential efficacy of anti-HBV vaccine ther apy. No side-effect or vaccine-induced escape-mutants occured during t he follow-up. In summary, serum HBV DNA disappeared in 28 of the 46 pa tients (60.9%) who were given vaccine therapy, with (64.2%) or without (55.6%) Interferon. These results are not different at 6 months and a t the end of follow-up from those of 43 HBsAg chronic carriers who wer e given only an antiviral treatment. Active immune therapy against HBV appears efficient and less expensive than antiviral therapies in stop ping HBV replication. Such results need to be confirmed by the complet ed results of our controlled, randomized trial which is now conducted in our unit.