LAMIVUDINE TREATMENT CAN RESTORE T-CELL RESPONSIVENESS IN CHRONIC HEPATITIS-B

High viral and/or antigen load may be an important cause of the T cell hyporesponsiveness to hepatitis B virus (HBV) antigens that is often observed in patients with chronic HBV infection. Reduction of viral an d antigen load by lamivudine treatment represents an ideal model for i nvestigating this hypothesis. HLA class II restricted T cell responses and serum levels of HBV-DNA, HBsAg, and HBeAg were studied before and during lamivudine treatment in 12 patients with hepatitis B e antigen positive chronic active hepatitis B to assess possible correlations b etween viral and/or antigen load and vigor of the T cell response. Cel l proliferation to HBV nucleocapsid antigens and peptides and frequenc y of circulating HBV nucleocapsid-specific T cells were assessed to ch aracterize CD4-mediated responses. A highly significant enhancement of the CD4-mediated response to HBV nucleocapsid antigens was already de tectable in most patients 7-14 d after the start of lamivudine treatme nt. This effect was dramatic and persistent in 10 patients but undetec table in 2, It occurred concomitant with a rapid and marked reduction of viremia, Interestingly, lamivudine also enhanced the responses to m itogens and recall antigens, showing that its effect was not limited t o HBV-specific T cells. In conclusion, an efficient antiviral T cell r esponse can be restored by lamivudine treatment in patients with chron ic hepatitis B concurrently with reduction of viremia, indicating the importance of viral load in the pathogenesis of T cell hyporesponsiven ess in these patients. Since lamivudine treatment can overcome T cell hyporeactivity, combining lamivudine with treatments directed to stimu late the T cell response may represent an effective strategy to induce eradication of chronic HBV infection.