Idiopathic Pulmonary Fibrosis and High Prevalence of Serum Antibodies to Hepatitis C Virus

Abstract

The prevalence of serum antibodies to hepatitis C virus (HCV) was assessed by an enzyme-linked immunosorbent assay (ELISA) in 66 patients (46 male and 20 female; mean age +/- SEM, 61.5 +/- 10.1 yr) with idiopathic pulmonary fibrosis (IPF). Nineteen (28.8%) were positive for this test. The frequency of HCV positiveness was significantly higher in the patients with IPF than in the 9,464 control subjects, whose ages were comparable with those of the patients (3.66%, p less than 0.05). Importantly, 12 of the 19 patients with IPF and positive ELISA results (63.2%) had positive results on the Chiron recombinant immunoblotting assay (RIBA), which is known to be more specific for HCV. We judged the 12 perceptible reactions as eight reactive and four indeterminate. When we examined liver function retrospectively, only two of eight patients who tested positive for the HCV had liver dysfunction, suggesting that anti-HCV positivity in IPF was not observed as a result of liver disease. These results lead us to speculate that HCV infection may play an important role in the pathogenesis of IPF, or that the sera of patients with IPF may contain some antibody against an unknown epitope and cross-react with the anti-HCV assay.

Sicca syndrome associated with hepatitis C virus infection

“…Various immunologic and clinical abnormalities have been described in patients with chronic hepatitis C: mixed cryoglobulins, autoimmune thyroiditis, pulmonary fibrosis, polymyositis, and vasculitis (2,5,7,8,22). Moreover, asymptomatic immunologic changes have been reported in this type of infection, such as RF in 71% of patients and ANA in 22% of patients (9).…”

“…While mixed cryoglobulins have been described in 50% of patients with chronic HCV infection (l), 53-82% of patients with mixed cryoglobulinemia had chronic HCV infection, and this virus is now considered to be an etiologic agent for mixed cryoglobulinemia (2)(3)(4). Latent autoimmune thyroid disease, glomerulonephritis, polymyositis, and pulmonary fibrosis have been reported in association with HCV (5)(6)(7)(8). Lymphocytic sialadenitis has been reported in patients with chronic HCV infection, but the clinical and immunologic status of those patients was not described (9).…”

Polymoyositis, lung fibrosis, and cranial neuropathy in a patient with hepatitis C virus infection

“…This is a systemic vasculitis that occurs due to circulating HCV-containing immune complexes (6) and is characterized by various clinical symptoms including interstitial lung involvement, generally asymptomatic (8). Moreover, a significantly high frequency of exposure to HCV has been reported in patients with "idiopathic" lung fibrosis (9). HCV infection of lymphocytes (2) could be regarded as the remote event leading to the B cell expansion responsible for various autoimmune phenomena and various forms of organ damage, including lung fibrosis.…”

“…Kyle RA, Linos A, Beard CM, Linke RP, Gertz MA, O'Fallon WM, Kurland LT: Incidence and natural history of primary amyloidosis in Olmsted County, Minnesota, 1950through 1989. Blood 79: "-1822, 1992 Polymyositis, lung fibrosis, and cranial neuropathy in a patient with hepatitis C virus infection…”

Treatment of immune thrombocytopenia associated with interferon therapy of hepatitis C with the anti-CD20 monoclonal antibody, rituximab

“…Patients with HCV-related thrombocytopenia often have clinical manifestations of other immunologic disorders, including cryoglobulinemic vasculitis [11], glomerulonephritis [12,13], pulmonary fibrosis [14], and the development of B-cell neoplasms [15]. Laboratory findings can include mixed cryoglobulins, elevated rheumatoid factor, antinuclear antibodies, anticardiolipin antibodies, and monoclonal gammopathies [11][12][13].…”