Demonstration of an association between detection of IgG antibody reactivity towards the C-terminal region of the preS1 protein of hepatitis B virus and the capacity to respond to interferon therapy in chronic hepatitis B

Background and Aim: The treatment of hepatitis B virus (HBV) remains complex, with somewhat unpredictable responses. The aim of this study was to determine the predictive value of the pretreatment presence of circulatory antibodies towards a synthetic peptide mimicking the amino acids 94-117 of the preS1 protein of HBV and the capacity to respond to alpha-inteferon (IFN-alpha) treatment. Methods: The anti preS1(94-117) antibodies were measured by a peptide-based enzyme-linked immunosorbent assay ( ELISA) and the response to INF-alpha therapy was judged by the effect on the viral kinetics as measured by an assay based on quantitative polymerase chain reaction during the treatment and follow up. Results: We found a significant ( P < 0.001) correlation between the pretreatment presence of anti preS1( 94-117) antibodies and a decrease in viral levels on follow up after the end of IFN-alpha therapy. The combined response of HBV DNA suppression ( P < 0.001), hepatitis B e antigen ( HBeAg) loss ( P < 0.0001), anti-HBe seroconversion (P < 0.005) and AST aminotransferase normalization ( P < 0.01) was also highly associated with the pretreatment presence of anti preS1(94-117) antibodies. Conclusion: The positive predictive value (PPV) of anti preS1(94-117) in determining a virological response was 83% and the negative predictive value ( NPV) was 100%, indicating that in the absence of pretreatment anti preS1 reactivity virtually no patient has the capacity to respond to IFN-alpha therapy. Our findings may help to improve the efficacy of INF-alpha therapy for chronic hepatitis B (CHB) by guiding the selection of patients for treatment and optimizing the clinical management of the individual patient.