Autoimmunity against pancreatic islets and other tissues before and after interferon-alpha therapy in patients with hepatitis C virus chronic infection

OBJECTIVE - The aim of the study was to investigate the prevalence of clini cal and latent autoimmune diseases in Italian patients with hepatitis C vir us (HCV) chronic infection before and after treatment with interferon-oc (I FN-alpha). RESEARCH DESIGN AND METHODS - The evidence of clinical autoimmune disease a nd the presence of autoantibodies were assessed in 70 patients with HCV chr onic infection. Autoantibodies to islet cell (ICA), glucagon-producing cell s (GCA),parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA), liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth m uscle (SMA) were tested using the classic indirect immunofluorescence techn ique. Autoantibodies to GAD (GADAb), second islet cell autoantigen (IA2-Ab) , and insulin (IAA) were tested by radioimmunoassay, and thyroid microsomal autoantibodies (TMHA) and thyroglobulin autoantibodies (TGHA) were assesse d by hemoagglutination test. RESULTS - None of the 70 patients studied showed evidence of clinical disea se before treatment with IFN-a. However, 1 (1.4%) patient was positive for ICA, 2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%) for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGH A. These frequencies were not significantly different when compared with he althy control subjects. There were 29 (41%) patients who were positive for IAA at low titers compared with 2% of the control subjects (significantly d ifferent P < 0.0001). ICA titers of one patient positive for ICA/GADAb incr eased during the IFN-alpha therapy, and the patient developed type 1 diabet es 5 months after the beginning of treatment. IAA levels did not change dur ing the course of treatment, and none of the IAA(+) patients developed diab etes. Thyroid autoantibody titers increased in 3 of the 4 initially positiv e patients, with 1 patient becoming positive and 2 thyroid antibody-positiv e patients developing overt hypothyroidism during IFN-alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to other auto-anti gens did not change during the course of treatment. CONCLUSIONS - We have not found an increased frequency of clinical or laten t autoimmune diseases in patients with chronic HCV infection. However, this study suggests that screening patients for autoantibodies tin particular t hyroid and pancreas) before and during IFN-alpha therapy may be useful in a ssessing the risk of patients developing autoimmune disease.