Autoimmune Phenomena and Hepatitis C Infection


Synopsis: Not only is hepatitis C viral infection strongly associated with cryoglobulinemia, but this review cites studies associating HCV with positive anti-nuclear antibodies and a variety of other autoantibodies.

Source: McMurray RW, Elbourne K. Semin Arthritis Rheum 1997;26:689-701.

It is generally well known that the rate of positive tests for autoantibodies, such as rheumatoid factor (RF) and anti-nuclear antibodies (ANA), are increased in chronic infectious illnesses, the prototype being subacute bacterial endocarditis. Perhaps less well appreciated is that hepatitis C virus (HCV) infection has been associated with many autoimmune phenomena. McMurray and Elbourne provide a review of the literature on HCV and autoimmunity that would be helpful to anyone interested in the topic. The references include a few reports from 1996 and many from 1994-1995. They note estimates of rates of positive ANA of 10-30%, of cryoglobulin in 36%, and of RF in 71% of patients who have positive HCV serology. Other antibodies that have been reported to be present more frequently in HCV-infected patients include anti-phospholipid (anti-cardiolipin), anti-thyroid, anti-liver/kidney-microsome, and cryoglobulin (predominantly mixed cryoglobulinemia). Despite the possibility of misdiagnosis of a patient with fever, rash, arthritis, and glomerulonephritis as having systemic lupus erythematosus (SLE), one study cited by the authors found only a 6% prevalence of serologic evidence of HCV infection in lupus patients, a rate that was not significantly different from controls.1 Also cited are reports of alpha diseases, such as thyroiditis, which are presumed to have an autoimmune pathogenesis.


A frequent reason for rheumatology consultation is the finding of a positive ANA or RF test. An article that addressed the orphan ANA problem several years ago, before serologic diagnosis of HCV was used in clinical practice, reported finding a variety of previously undiagnosed diseases and disorders, which the authors felt were associated with the positive ANA. In the 276 patients evaluated by one community-based rheumatologist, only three had hepatitis, one with chronic active hepatitis, and the other two with "viral hepatitis."2

McMurray and Elbourne make the point that HCV infection should be added in a prominent place in the list of causes of autoantibodies, especially ANA and RF. Since a sizeable number of patients with HCV infection have no identifiable risk factors, it may be prudent to check for serologic evidence of HCV infection in patients with positive ANA or RF results, especially if they do not have a classic rheumatic, collagen-vascular, or connective tissue disease that accounts for the presence of an ANA or RF.


1. Marchesoni A, et al. Clin Exp Rheumatol 1995;13: 267-268.

2. Shiel WC, Jason M. J Rheumatol 1989;16:782-785.