Co-occurrence of HBsAg and anti-HBs is said to be rare and is usually explained by assuming two consecutive infections with incomplete immunity following the first infection. In order to determine the frequency of co-occurrence of HBsAg and anti-HBs and to validate the two-infection hypothesis, a group of 89 Dutch patients of North-European local race with HBsAg(+) biopsy-documented chronic hepatitis were tested for the presence ofanti-HBs and risk factors for hepatitis B. HBsAg and anti-HBs were determined using radio immuno assay (AUS.RIA II, AUSAB); subtyping was also done with RIA after neutralization with a panel of specific antigen or antibody subtypes according to the method of Hoofnagle et al. (1977). Anti-HBs was found in 32 patients (36 %). In 19 out of 25 patients with a reliable subtyping of HBsAg and anti-HBs, the co-occurrence of HBsAg/ad and antiy was found; the combination HBsAg/ay and anti-d was present in one patient; the other 5 patients exhibited complex patterns of antibody. Comparison between anti-HBs(+) and anti-HBs(-) patients revealed no differences in various categories of risk factors for hepatitis B infection (transfusion, medical profession, homosexual contacts, drug abuse, etc.) but a significant correlation was found between the prevalence of anti-HBs and the histologic progression of the liver disease (anti-HBs positivity in carriers: 3/23; CPH : 4/20; CAH :20/41 ; cirrhosis: 5/5).
Thus, co-occurrence of HBsAg and anti-HBs is not rare, but its frequency depends on the histologic stage of the liver disease. No support could be found for the two-infection hypothesis. We, therefore, believe that d and y antigens are present on HBsAg-bearing proteins and that one or the other of these subdeterminants is hidden in HBsAg-bearing particles dependent on the virus strain. The masked subdeterminant becomes antigenic after degradation of liver cells in advanced disease.