Autoimmune mechanisms in chronic hepatitis B and delta virus infections

To investigate the possibility that hepatitis delta virus infection may be responsible for, or enhance, the autoreactivity seen in patients chronically infected with hepatitis B virus. Sera from 68 patients with chronic hepatitis B infection, 27 of whom had concomitant delta virus (HDV) infection and 19 of whom were infected with hepatitis C virus (HCV), were screened for (1) the non-organ-specific autoantibodies usually associated with autoimmune hepatitis, (2) antibodies against the putative autoantigen, GOR, which have been described in patients with HCV infection and (3) antibodies against a hepatocyte-specific autoantigen, the asialoglycoprotein receptor (ASGP-R). Anti-GOR antibodies were detected using an enzyme-linked immunosorbent assay against a synthetic GOR peptide, non-organ-specific autoantibodies using standard indirect immunofluorescence and anti-ASGP-R antibodies using a radioimmunoassay. Liver-specific autoreactivity, manifested by circulating anti-ASGP-R antibodies, was found in 41 (60.3%) patients and correlated independently with the histological severity of liver damage but not with HDV infection. In contrast, non-organ-specific autoantibodies (antinuclear, anti-smooth muscle, anti-gastric parietal cell and anti-liver-kidney microsomal type 1) were found (mostly at low titres) in only 15 (22.1%) patients and did not correlate with either HDV infection or with histological severity. Basal cell layer antibodies and type 3 liver-kidney microsomal antibodies were not seen in any patient. Antibodies against GOR were found in only five (7.4%) patients, all of whom showed evidence of exposure to HCV. The findings suggest that HBV-induced liver-specific autoreactions might contribute to periportal liver damage in patients with chronic hepatitis B infection, but do not support the notion that the delta virus can induce an autoimmune response or that HCV coinfection suppresses autoreactivity in this situation.