In order to determine the relationship between the presence of pre‐S1 and pre‐S2 proteins and the level of hepatitis B virus (HBV) replication, a study of 94 HBsAg chronic carriers, 15 anti‐HBe positive patients who suffered a viral reactivation and 12 HBeAg, HBV‐DNA positive cases under antiviral therapy, has been carried out. Pre‐S1 and pre‐S2 antigens were detected by RIA using polystyrene beads coated with anti‐preS1 or anti‐preS2 (Dr W. Gerlich, Göttingen) and 125I‐anti‐HBs as tracer. The presence of pre‐S1 and pre‐S2 antigens was detected in 74 (79%) and 85 (90%), respectively, out of the 94 HBsAg chronic carriers included. The level of these antigens was significantly higher in HBeAg, HBV‐DNA positive patients than in the other patients (p<0.05). Among anti‐HBe positive patients suffering a reactivation, a significant increase of pre‐S1 and pre‐S2 levels was observed, concurring with ALT exacerbation and HBV‐DNA positivity. After reactivation, the level of pre‐S antigens returned to the basal values. A significant decrease in pre‐S antigen levels (p<0.05) among patients who respond to recombinant interferon therapy was observed, while no changes were detected among non‐responder cases. The detection of pre‐S1 and pre‐S2 antigens in serum is more frequent in those patients with high viral replication. Furthermore, among anti‐HBe carriers with a viral reactivation, synthesis of pre‐S antigens takes place again.

Antibody directed against HBsAg carries idiotypic determinants that may induce an autoantiidiotype antibody response. We describe a solid-phase radioimmunoassay which allows specific detection of either IgG or IgM antibody to antibody directed against HBsAg. Among 138 chronic hepatitis B virus carriers, IgG autoantiidiotype was detected in 98 (71%) and IgM autoantiidiotype in 10 (80%). The autoantiidiotype reaction was blocked with antibody directed against HBsAg after removal of immune complexes by polyethylene glycol precipitation. The prevalence and levels of both classes of autoantiidiotype antibodies were highest in patients with hepatitis B virus DNA or HBeAg in serum. During follow-up, patients who lost hepatitis B virus DNA and HBeAg from serum had lower titers of autoantiidiotype and were less likely to have autoantiidiotype than patients who persisted in having hepatitis B virus DNA and HBeAg in serum. Thus, the presence and titer of autoantiidiotype correlated with serologic evidence of active viral replication in chronic hepatitis B. These findings suggest that the antibody directed against HBsAg response may play a role in modulating viral replication in chronic hepatitis B.

To determine the possible changes in the presence and level of anti-idiotype (anti-Id) antibodies against anti-HBs induced by recombinant interferon (rIFN) therapy in chronic hepatitis B virus (HBV) infection, a study of patients under rIFN treatment has been carried out. A total of 62 (38 treated and 24 controls), HBeAg and HBV-DNA positive HBsAg carriers were tested serially for the presence of IgG and IgM anti-Id antibodies. According to serological evolution, treated patients were divided in responders (HBeAg and HBV-DNA became negative) (n = 18) and nonresponders (n = 20). Control patients were also classified as having spontaneous seroconversion (n = 11) and without changes (n = 13). Basally all patients had IgG and IgM anti-Id. At the end of the follow-up period (15th month), a significant decrease was observed in the percentage of cases positive to anti-Id among rIFN-responders (IgG, 67%, p less than 0.01; IgM, 44%, p less than 0.001). In contrast, only one nonresponder lost IgM anti-Id during the study. Among controls, only one with spontaneous loss of HBV-DNA and HBeAg clearance became negative to both IgG and IgM anti-Id. In addition, in the basal sample, the rIFN-responders had significantly lower anti-Id levels than the nonresponders (p less than 0.05). Similar results were obtained when comparing the controls with or without spontaneous response (p less than 0.05). Furthermore, a significant decrease in the anti-Id levels among the rIFN responders at the 9th month was detected (p less than 0.01). In summary, the anti-Id antibodies decreased significantly in patients who became HBV-DNA negative following rIFN administration. This result confirms the close relationship between HBV replication and the anti-idiotype against anti-HBs.

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