Antibody‐directed complement‐mediated cytotoxicity to hepatocytes from patients with chronic hepatitis B

SUMMARY The susceptibility of hepatocytes from patients with chronic hepatitis B to complement‐dependent cytotoxicity mediated by heterologous antibodies to hepatitis B virus core (anti‐HBc) and surface (anti‐HBc) antigens and to hepatic asialoglycoprotein receptor was examined using a micro‐cytotoxicity assay. The anti‐HBc‐induced cytotoxicity was found to be markedly enhanced against hepatocytes isolated from patients with chronic active hepatitis (72·6 ± 9·5% (mean±s.e.m.); n= 6) over that against hepatocytes from individuals with chronic persistent hepatitis or inactive liver cirrhosis (40·6 ± 18·6%; n= 4) (P= 0·019). Overall, values of the anti‐HBc‐directed cytotoxicity were higher in patients positive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg), Hepatocytotoxicity was also exerted by anti‐HBs and anti‐asialoglycoprotein receptor antibodies in the presence of complement, but it was not seemingly related to disease activity. These results indicate that hepatitis B virus core and surface antigens and asialoglycoprotein receptor at the hepatocyte surface can be recognized by antibodies, and raise the possibility that complement‐dependent cytolysis may contribute to the injury of hepatitis B virus‐infected hepatocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti‐HBc antibody‐directed complement‐mediated cytotoxicity than those with inactive liver histology.