OBJECTIVETo study the causes of poorer antiviral response to neutralizing anti-interferon-alpha antibodies (NA) in male chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha).

METHODSTwo hundred sixty-nine patients (198 males and 71 females) with histologically proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6-37 (median 10.0) months. For each patient, serum HBV DNA levels were detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay, and NA with an antiviral neutralizing biological assay during therapy.

RESULTSNA was found in 70 (35.4%) of the 198 males and in 15 (21.1%) of the 71 females during treatment (x2 = 4.894, P = 0.027). At the end of treatment combined-response was achieved in 21 (24.7%) of the 85 NA-positive patients and in 100 (54.3%) of the 184 NA-negative cases (x2 = 20.642). Stratification analysis by NA showed that combined-response rate was significantly lower in males than in females (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among NA-positive patients while it was similar in males and in females (50.8%, 65/128, vs. 62.5%, 35/56, x2 = 2.156) among NA-negative patients. In stratification analysis by gender, it was significantly lower in NA-positive patients than in NA-negative ones (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among males but there was no significant difference between combined-response rates among females.

CONCLUSIONThe poorer antiviral response to recombinant interferon-alpha in male chronic hepatitis B patients than in female patients is related to the neutralizing anti-interferon antibodies.