Quantitative analysis of IgM anti-HBc in chronic hepatitis B patients using a new ''gray-zone'' for the evaluation of ''borderline'' values

Background/Methods. In order to define the clinical significance of borderline levels of IgM anti-HBc in chronic hepatitis BE patients, we followed up 89 untreated. hepatitis B patients (19 HBeAg pos and 70 anti-HBe pos) for 1 year, with monthly monitoring of IgM anti-HBe using a highly sensitive quantitative microparticle enzyme immunoassay (IMx CORE-M, Abhott). As a control group we used 304 healthy subjects: 150 HBsAg negative and anti-HBc/anti-HBs positive, and 154 without markers of HBV infection. The statistical analysis performed by Receiver Operating Characteristic curve indicated the 100% sensitivity cutoff at 0.081 IMx index and 100% specificity cutoff at 0.358 IMx index. Results: We could define the range of a chronic hepatitis B ''gray-zone'' between 0.100 [80.6% specificity (95% CI, 76.2%-85%), 96.5% sensitivity (95% CI, 92.5%-100%)] and 0.200 [95.7% specificity (95% CI, 93.4%-95%) and 78.7% sensitivity (95% CI, 70.2%-87.2%)] of the IgM anti-HBc-IMx index, In fact, none of the chronic hepatitis B patients had IgM anti-HBc-IMx values persistently below 0.100 during the follow-up, whereas 57.3% had values persistently higher than 0.200, In 38.2%, IgM anti-HBe values occasionally fell within the ''gray-zone'' limits. In the remaining four patients (4.4%), the results overlapped the ''gray-zone'' values. Conclusions: These results suggest that the use of a chronic hepatitis B ''gray-zone'' for values of quantitative IgM anti-HBc assays helps to distinguish ''true healthy carriers'' from asymptomatic chronic anti-HBe positive hepatitis B patients who have been shown to have temporary remissions of liver disease and frequently undetectable serum HBV-DNA.