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.
OBJECTIVE
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.


CONCLUSIONS
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.
Hellström
Ulla
U
Department of Communicable Disease Control and Prevention, Karolinska Hospital, Stockholm, Sweden.
Lindh
Magnus
M
Krogsgaard
Kim
K
Sylvan
Staffan
S
D000328:Adult; D000937:Antigen-Antibody Reactions; D000998:Antiviral Agents / Q000627:therapeutic use*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood* / Q000276:immunology*; D016898:Interferon-alpha / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000276:immunology*
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D016898:Interferon-alpha; D011498:Protein Precursors; C050806:presurface protein 1, hepatitis B surface antigen