To our knowledge, no data have been reported concerning the synchronous effects of entecavir on the serial measurement of peripheral blood lymphocyte subpopulations and serum HBV DNA concentrations in patients with chronic hepatitis B. During entecavir-therapy, we detected a shift in the CD4+/CD8+ ratio, owing to a relative decrease in the number of CD8+ cells and increase in the number of CD4+ lymphocytes, and an increase in the number of CD3+ cells, concomitantly with a quantitative reduction in viral replication. Here, CD8A is linked to chronic hepatitis B virus infection.