ANTIBODY-DIRECTED COMPLEMENT-MEDIATED CYTOTOXICITY TO HEPATOCYTES FROM PATIENTS WITH CHRONIC HEPATITIS-B

The susceptibility of hepatocytes from patients with chronic hepatitis B to complement-dependent cytotoxicity mediated by heterologous antib odies to hepatitis B virus core (anti-HBc) and surface (anti-HBs) anti gens and to hepatic asialoglycoprotein receptor was examined using a m icrocytotoxicity 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, v alues of the anti-HBc-directed cytotoxicity were higher in patients po sitive for HBcAg in hepatocytes and seropositive for hepatitis B virus e antigen (HBeAg). Hepatocytotoxicity was also exerted by anti-HBs an d anti-asialoglycoprotein receptor antibodies in the presence of compl ement, but it was not seemingly related to disease activity. These res ults indicate that hepatitis B virus core and surface antigens and asi aloglycoprotein receptor at the hepatocyte surface can be recognized b y antibodies, and raise the possibility that complement-dependent cyto lysis may contribute to the injury of hepatitis B virus-infected hepat ocytes. The data also suggest that liver cells of patients with severe chronic hepatitis might be more susceptible to anti-HBc antibody-dire cted complement-mediated cytotoxicity than those with inactive liver h istology.