Hepatitis B virus markers in anti-HBc only positive individuals

Isolated reactivity to hepatitis B virus (HBV) core antigen (anti-HBc) is o bserved relatively frequently in immunocompromised individuals, intravenous drug abusers (IVDA), and in the presence of HCV infection. The reason for the lack of HBsAg is not clear. The aim of the present study was to investi gate which factors (genetic variability of S gene, low-level HBsAg, and imm une complexes may be responsible for the failure of HBsAS detection with co mmercial HBsAg screening assays. Dilution series of two recombinant HBsAg e scape mutants and dilutions of serum samples from chronic HBV carriers with multiple insertions in the a determinant and different HBsAg subtypes were tested with a highly sensitive assay that detects wild-type HBsAS (Elecsys HBsAg, Roche Diagnostics, Penzberg, Germany) and two assays that detect HB V wild-type and escape mutants (Murex HBsAS Version 3, Murex and Enzygnost HBsAg 5.0, Dade Behring, Marburg, Germany). Elecsys HBsAg showed in compari son to Murex HBsAg Version 3 and Enzygnost HBsAg 5.0 a reduced sensitivity for escape mutant detection. On the other hand, the best performance for HB sAg subtype detection was obtained with Elecsys HBsAS. In the second part o f the study, a selected panel of isolated anti-HBc reactive (n=104) serum s amples (AxSYM Core) was submitted to testing by Elecsys HBsAg, Murex HBsAS Version 3, Enzygnost HBsAg 5.0, and HBsAS detection after immune complex di ssociation (ICD) and anti-HBs determination with two different assays (AxSY M Ausab and Elecsys Anti-HBs). To assess the specificity of anti-HBc test r esults, all the samples were tested by a second anti-HBc assay (Elecsys Ant i-HBc). Quantitative HBV DNA detection was undertaken with a commercially a vailable HBV PCR assay (Amplicor HBV Monitor). HCV infection was present in 65.4% of anti-HBc only reactive individuals. Five AxSYM Core positive samp les were negative by Elecsys Anti- HBc. Overall, 15(14.4%) AxSYM Ausab nega tive samples gave positive results with Elecsys Anti-HBs (median value: 21 IU/ml). No low-level HBsAg carrier was detected among the isolated anti-HBc reactive individuals with Elecsys HBsAg. There was no evidence for the pre sence of immune complexes. Only one sample was repeatedly reactive by the M urex HBsAg, suggesting that the a mutant form of HBsAg was responsible for the isolated anti-HBc reactivity, however neutralisation assay was not inte rpretable and HBV DNA PCR was negative. Fifteen (14.4%) anti-HBc only posit ive individuals were HBV DNA carriers with concentrations ranging from 800 to more than > 4,000,000 copies of viral DNA/ml. In conclusion, the most pr obable explanations for isolated anti-HBc reactivity in our study group are a possible interference of HBsAg synthesis by HCV infection (65.4%) and di vergence of results of anti-HBs assays (14.4%). There is no evidence for th e presence of low-level HBsAg carriers and immune complexes. HBsAg mutants cannot be excluded definitively by the test strategy used in the present ev aluation. (C) 2001 Wiley-Liss, Inc.