Specific liver autoreactivity in schistosomiasis mansoni.

To investigate the possible involvement of autoimmune mechanisms in the development of hepatosplenic schistosomiasis (HSS), 234 patients with chronic Schistosoma mansoni infections were screened for a wide range of non-organ-specific autoantibodies as well as for antibodies reacting with the GOR peptide and with a liver-specific autoantigen, the hepatic asialoglycoprotein receptor (ASGP-R). Thirty-five (15.0%) were seropositive for antinuclear, smooth muscle or gastric parietal cell antibodies at low titres (< or = 1:80), and 15/176 (8.5%) had anti-GOR, all of whom had concomitant hepatitis C viral (HCV) infections. Anti-ASGP-R was found in 64 (27.4%) of the 234 patients at titres similar to those found in 18 untreated auto-immune hepatitis patients studied concurrently. Anti-ASGP-R seropositivity occurred significantly (P < 0.005) more frequently in patients with HSS (62/190, 32.6%) than in those with hepatointestinal schistosomiasis (2/44, 4.5%), but did not correlate with severity of liver disease or with the presence of the non-organ-specific autoantibodies. Anti-ASGP-R was found significantly (P < < 0.0005) less frequently in HSS patients who had had a splenectomy for portal hypertension (5/86, 5.8%) than in those who had not had a splenectomy (57/104, 54.8%). The findings suggest that liver-specific autoreactivity may play a role in the development of HSS.

Autoimmune mechanisms in chronic hepatitis B and delta virus infections.

OBJECTIVE: 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. DESIGN: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Virus-induced autoimmunity in hepatitis C virus infections: a rare event.

Serial serum samples from 16 Italian patients presenting with acute hepatitis C virus (HCV) infections (which progressed to chronic hepatitis in six) were screened for the non-organ-specific autoantibodies most frequently associated with autoimmune hepatitis (AIH), as well as for antibodies against the hepatic asialoglycoprotein receptor (ASGP-R) and against the GOR peptide. One patient had low titres (1:10-1:80) of liver-kidney microsomal (LKM-1) antibodies during the recovery phase and three others had transient low titres of anti-smooth muscle (IgM class, 1:10) or anti-ASGP-R (1:150-1:300). Anti-GOR was detected in 43 (65%) of 66 sera from 13 of these patients. There was no correlation between any of these findings and progression to chronicity. By comparison, 18 patients with AIH studied concurrently before institution of immunosuppressive therapy all had antinuclear and/or smooth muscle antibodies, or LKM-1, at 1:40-1:640 and anti-ASGP-R at 1:300-1:2,100. None of these 18 had evidence of HCV infection and all were seronegative for anti-GOR. The findings indicate that the autoantibodies usually associated with AIH are rare in HCV infections but the virus can very occasionally induce a transient autoimmune response. Anti-GOR appears to be an antibody specifically related to HCV infection and is probably not a marker of induced autoimmunity, and it does not predict progression to chronic hepatitis.

Antibodies to hepatitis C virus in autoimmune liver disease: evidence for geographical heterogeneity.

To resolve conflicting reports about the occurrence of antibodies against hepatitis C virus (HCV) in patients with autoimmune chronic active hepatitis (AI-CAH), sera from UK and Italian patients were tested with the original anti-HCV assay (Ortho) and a novel anti-HCV assay (UBI) based entirely on synthetic HCV peptides. 28 (60%) of 47 Italian patients with type-1 AI-CAH were anti-HCV-positive by Ortho ELISA, 25 of whom were also strongly positive by the UBI assay. 15 (60%) of 25 UK patients with type-1 AI-CAH were HCV-positive by Ortho ELISA but only 2 were positive by the UBI assay. Similarly, 29 (88%) of 33 Italian patients with type-2 AI-CAH, but 0 of 10 UK patients, were very strongly anti-HCV-positive with the UBI assay. Italian patients with AI-CAH appear to have a high frequency of genuine exposure to HCV, whereas seropositivity by the Ortho HCV ELISA in UK patients is likely to represent a false-positive result. These findings indicate important geographical and/or genetic influences in autoimmune liver disease among different populations.