Development of a second generation monoclonal immunoradiometric assay. Increased sensitivity leads to enhanced detection of hepatitis B viral infection.

We have developed and employed a second generation monoclonal immunoradiometric assay (M2-IRMA) using antibodies of high affinity for epitopes that reside on hepatitis B surface antigen (HBsAg). This assay is capable of detecting as little as 15 pg/ml of HBsAg in serum. Improvements in sensitivity over a first generation immunoradiometric assay (MI-IRMA) was achieved by increasing the sample volume and time of incubation, and subjecting the reaction to a mechanical rotary devise. We then studied 164 subjects with chronic hepatitis, 105 with cirrhosis, 67 with hepatocellular carcinoma, six with acute hepatitis A, seven with acute hepatitis B, 167 chronic carriers of hepatitis B virus (HBV) and 235 healthy individuals from Japan and compared the results of the M2-IRMA to a conventional polyclonal radioimmunoassay (P-RIA). By using a more sensitive assay design (M2-IRMA), a significant number of additional cases of HBV infection heretofore unsuspected in the etiology of chronic liver disease were identified. We conclude that improvement in assay sensitivity for HBsAg is important in the serologic diagnosis of HBV in patients with chronic hepatitis, cirrhosis and hepatocellular carcinoma.