Patients with chronic liver disease and hepatocellular carcinoma may lack serological evidence of previous hepatitis B virus infection. The purpose of the present study was to test the hypothesis that circulating immune complexes may interfere with the detection of low levels of HBsAg in such patients. Sera from 190 patients were initially screened for the presence of circulating immune complexes. Patients belonged to three clinical categories: asymptomatic HBsAg carriers (50 patients), chronic liver disease (30 patients) and hepatocellular carcinoma (110 patients). Forty-one of the group of 190 patients (21%) were positive for circulating immune complexes. Sera from 21 patients were selected for further evaluation. The sera of 13 chronic liver disease or hepatocellular carcinoma patients (HBsAg negative, hepatitis B virus-DNA negative, with or without evidence of previous hepatitis B virus infection) and eight HBsAg positive carriers (four asymptomatic, three with chronic liver disease and one with hepatocellular carcinoma) were passed through a Clq affinity column (first column) to remove circulating immune complexes. Unbound material was then passed through a monoclonal IgG2a anti-HBs affinity column (second column). Unbound material (following both columns) contained free HBsAg, as determined by monocolonal radio-immunoassay, in eight patients in whom HBsAg had been undetectable in the original serum. Removal of circulating immune complexes from the serum of the three HBsAg positive patients with chronic liver disease also caused a significant increase in measurable circulating HBsAg compared with the original serum. SDS-polyacrylamide gel electrophoresis analysis revealed HBsAg in the eluates of the Clq affinity columns, as well as in the eluates of the monoclonal anti-HBs columns of all HBsAg positive patients, and in all HBsAg negative patients in whom the "unmasking" phenomena occurred. These results suggest that HBsAg may elude detection by radioimmunoassay in the presence of immune complexes and that removal of circulating immune complexes prior to radioimmunoassay testing may increase the rate of HBsAg detection. Hence, failure to detect circulating HBsAg by conventional radioimmunoassay does not necessarily exclude an HBsAg carrier state.
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