The authors describe the clinical case of a naive patient with chronic hepatitis HBV-related (CHB) HBeAg negative, treated with Telbivudine (LdT) 600mg/day. After six months of treatment, as well as it determines rapid, profound and sustained suppression of HBV replication, LdT induced a progressive decline of HBsAg serum level and HBsAg loss, probably through an immune modulator effect. Recent studies have indicated the possible action of LdT on the immune system and specifically it would be able to stimulate Th1 lymphocyte subpopulation by increasing their cytokines production, thus playing a major role in cleaning the HBV infection. This aspect appears to be of much interest in clinical practice, because on-treatment HBsAg rapid decline >1 log10 IU/mL during the first year of treatment is highly predictive for future HBsAg clearance and CHB resolution.