Background/Purpose:

Joint pain is a common extra-hepatic manifestation of chronic hepatitis C (HCV) infection. HCV infection is often associated with the presence of autoantibodies such as rheumatoid factor (RF), seen in approximately 50% of patients, and anti-nuclear antibodies (ANA). Consequently, it can be difficult to distinguish HCV arthralgias from rheumatoid arthritis (RA), especially in early RA when erosions or joint space narrowing are often lacking. Recent studies suggest that antibodies to cyclic citrullinated peptides (anti-CCP antibodies) are highly specific for RA and are absent in patients with HCV arthralgias. In this study, we determined the sensitivity, specificity, and positive and negative predictive values of RF and anti-CCP antibodies for RA in patients with HCV arthralgias.

Methods:

We enrolled 97 patients with HCV and arthralgias (defined as pain in >3 joints) in this St. Louis VA Medical Center-based cross-sectional study. Patients were classified as HCV with RA (RA+) or HCV without RA (RA-) based on the presence of HCV antibodies, HCV RNA, or consistent liver biopsy, and meeting 1987 ACR criteria for the diagnosis of RA. Demographic, clinical and serologic information was collected on all patients during a standardized in-person medical evaluation. Patients were excluded if they had other major autoimmune extrahepatic manifestations of HCV (vasculitis, glomerulonephritis, monoclonal gammopathy, lymphoma or multiple myeloma) or were on current anti-viral treatment for HCV infection. Categorical and continuous variables were analyzed using Fisher’s exact test and t-tests respectively. A two-sided p-value < 0.05 demonstrated statistical significance.

Results:

Of the 97 patients with HCV and polyarthralgias, 17 met ACR criteria for RA (HCV RA+) and 80 had arthralgias from non-RA causes (HCV RA-): HCV arthralgia (31), osteoarthritis (28), crystalline arthropathy (9), spondyloarthropathy (7), fibromyalgia (3), polymyalgia rheumatica (2). Both groups were predominantly male (94.1% and 88.8%) and mainly consisted of African Americans in the HCV RA+ group (64.7%) and Caucasians in the HCV RA- group (50%). In the HCV RA+ group, 94.1% had synovitis, while only 6.9% of HCV RA- patients did.  RF was the most sensitive (100%) serology, while anti-CCP was highly specific (98.8%). Anti-CCP antibodies exhibited high positive and negative predictive values, 94.1% and 98.8% respectively. Synovitis had a high negative predictive value of 98.6%.

Conclusion:

The presence of anti-CCP antibodies and synovitis is highly specific for the diagnosis of RA in patients with HCV arthralgias.