DETECTION OF HEPATITIS-C VIRUS-ANTIGEN BY IMMUNOHISTOCHEMICAL STAINING - A HISTOLOGICAL MARKER OF HEPATITIS-C VIRUS-INFECTION

Hepatitis C virus has been recognized as a major cause of non-A, non-B viral hepatitis. Although serologic tests have been commercialized, n o specific histological or immuno-histochemical markers for hepatitis C virus infection are available for routine use. In an effort to detec t hepatitis C virus antigen in liver tissue we investigated the immuno -reactivity to monoclonal antibodies on frozen liver tissue from a chi mpanzee and patients with chronic non A, non B hepatitis. Monoclonal a ntibodies were developed in mice immunized with a synthetic peptide de rived from hepatitis C virus core antigen. One monoclonal antibody was reactive and showed typical cytoplasmic granules in chimpanzee hepato cytes. Using this monoclonal antibody a similar staining pattern was f ound in the liver biopsies of 21 out of 28 chronic non-A, non-B hepati tis patients, positive for hepatitis C virus-RNA and anti-HCV. The gra nular immuno-reactivity was abolished after pre-incubation of this mon oclonal antibody with infected chimpanzee liver or with hepatitis C vi rus synthetic peptide but not with normal chimpanzee or human liver ti ssue. There was no reactivity in four patients with hepatitis C virus- RNA-negative, anti-HCV-positive chronic non-A, non-B hepatitis, in 11 patients with chronic type B hepatitis or in 12 hepatitis C virus-RNA- negative, anti-HCV-negative patients with various liver diseases. Howe ver, staining was found in three out of four additional chronic type B hepatitis patients suspected of co-infection with non-A, non-B agents . This study provides evidence that a monoclonal antibody against a sy nthetic core peptide reacts specifically with hepatitis C virus antige n in situ. This monoclonal antibody may represent an important guide f or the histological diagnosis of hepatitis C virus infection. (C) Jour nal of Hepatology.