Approximately 130 million people worldwide are infected with hepatitis C virus (HCV). Although HCV primarily damages the liver, infection also causes multiple extrahepatic manifestations, including elicitation of autoimmune reaction, deposition of immune complexes and/or lymphoproliferation. Some patients develop arthritis, and many patients with HCV-related polyarthritis also meet the American College of Rheumatology criteria for rheumatoid arthritis (RA). Consequently, clinicians have noted an association between rheumatic diseases and chronic HCV infection. It has been difficult, however, to document this association in research studies.
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In a recently published study in PLoSOne, investigators Fu-Hsiung Su, MBBS, PhD, and colleagues describe their research to assess the risk of developing RA among patients with chronic HCV infection.1 The researchers studied patients in Taiwan, a country with a high prevalence of both HCV and hepatitis B virus (HBV) infections, as well as RA (52.4 per 100,000).
Dr. Su, an attending physician and assistant professor of Taipei Medical University in Taiwan, extracted data from the National Health Insurance Research Database, which includes 1 million patients randomly selected from all insured enrollees in Taiwan, and performed a nationwide population-based cohort study.
The investigators identified 249,460 patients with data from 2000–2011 for analysis. Of these, 49,892 patients had been diagnosed with chronic hepatitis virus infection: 10,253 had chronic HCV infection, 35,652 had chronic HBV infection alone, and 3,987 had chronic HCV/HBV dual infection.
Patients with the hepatitis virus were compared with 199,568 individuals who were matched for age, sex and calendar year, but did not have chronic hepatitis virus infection. The patients did not have a diagnosis of RA at baseline. The investigators noted any diagnosis of RA that occurred through 2011.
Cases of RA were defined on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes and their catastrophic disease registration. Impairment of liver function was also defined based on ICD-9-CM coding. The investigators did not control for family history, smoking, diet or hormone levels. They did perform bivariate statistical analysis of sex, age, geographic region, occupation, urbanization level, monthly income and Deyo’s Charlson Comorbidity Index.
After adjusting for covariates, the team found that chronic infection with HCV was associated with the development of RA (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.27–3.22). The increased risk remained significant even after the investigators restricted their analysis to patients who were prescribed disease-modifying antirheumatic drugs (HR 1.89, 95% CI 1.15–3.11). Men were more likely than women to have RA associated with chronic HCV infection (HR 1.88, 95% CI 1.08–3.25 for women; and HR 2.57, 95% CI 1.08–6.13 for men).
Additionally, researchers found that patients with chronic HCV infection and HBV/HCV dual infection were more likely to have RA than patients with non-chronic HBV and HCV infections, although chronic HBV infection was not associated with a high risk of developing RA.
This latter finding stands in contrast to previous studies that suggested chronic HBV infection may trigger the development of autoimmune rheumatic diseases. The investigators did find, however, that chronic HBV infection with persistent or periodic impairment of liver function was associated with RA (HR 2.64, 95% CI 0.84–8.28). (posted 1/23/15)
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
1. Su FH, Wu CS, Sung FC, et al. Chronic hepatitis c virus infection is associated with the development of rheumatoid arthritis: a nationwide population-based study in Taiwan. PLoSOne. 2014; 9(11): e113579.
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