In vivo immunization following virus suppression: a novel approach for inducing immune control in chronic hepatitis B

summary. Antiviral treatment of patients with active chronic hepatitis B may lead to significant reduction in morbidity and mortality. However, after stopping nucleoside therapy, relapse rates are high in those without acquired specific immunity. We have treated two chronic hepatitis B patients with in vivo immunization. In vivo immunization aims to optimize conditions for an effective immune response: following rapid and profound virus suppression by interferon-lamivudine combination therapy, lamivudine is withdrawn intermittently for 4 weeks during continued interferon therapy. In both patients with profound virus suppression a rapid rebound in viral replication was observed after lamivudine withdrawal; despite continued interferon. These periods of renewed viral replication were followed by rises in hepatitis activity. After re-introduction of lamivudine HBV DNA became undetectable by PCR followed by normalization of serum ALT. These observations are a stimulus to further explore the concept of in vivo immunization as a novel therapeutic approach for chronic hepatitis B.