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We investigated the effects of prophylactic nucleoside analogue treatment on HBV activation in patients with antibodies against core antigen ( HBc Ab+) patients undergoing immunosuppressive therapy. Patients (113), who were HBc Ab+, with various autoimmune diseases, undergoing immunosuppressive therapy, were divided into two groups. The control group, not treated with antivirals, and the prophylactic group, treated with antiviral drugs. The two groups were evaluated for changes in serum biochemical marker (alanine aminotransferase ALT), virological marker ( HBV DNA) and for seroconversion. In the control group, the number of patients with an increase in ALT in patients with isolated HBc Ab and HBc Ab and antibodies against HBs Ag ( HBs Ab +) were five (20.0%) and one (2.8%), respectively ( P < 0.05). There were six cases (24.0%) with an increase in HBV DNA in the isolated HBc Ab+ subgroup and one case (2.8%) in HBs Ab+/ HBc Ab+ subgroup ( P < 0.05). In the HBc Ab+ only population, six patients (24.0%) in the control group had an increase in HBV DNA compared with none in the antiviral prophylactic group ( P < 0.05). One patient (4.0%) with HBc Ab+ in the control group underwent an HBs Ag seroconversion when receiving immunosuppressive therapy for 18 months, while none in the antiviral prophylactic group underwent reversion to HBs Ag positivity ( P = 0.4949). Under immunosuppressive condition, the risk of HBV activation was much higher in patients with HBc Ab than in patients with both HBc Ab and antibodies to HBs Ab group. Antiviral prophylactic therapy could significantly reduce the risk of HBV reactivation. [ABSTRACT FROM AUTHOR]