One cannot rationally discuss HCV screening without consideration of screening strategies for other chronic viral infections such as HBV and HIV. We now know that HBV reactivation represents a growing and potentially fatal threat to patients on all forms of immunosuppression, including both nonbiologic DMARDS and all tumor necrosis factor (TNF) inhibitors and rituximab therapies.12 While oncologists and transplant physicians have clearly articulated guidelines, rheumatologists, as a profession, have not. We think it would be prudent to screen all patients going on to both nonbiologic and biologic DMARD therapies for HCV and HBV and, following the recent Centers for Disease Control and Prevention Guidelines, to test for HIV as well.13 Screening is inexpensive and nonpejorative and provides a wealth of useful information, not least of which could be the identification of a patient with a serious and yet highly treatable infection.
Testing for HCV is simple, with initial screening by HCV enzyme immunoassay (EIA) which has a high sensitivity and specificity. Positive EIA tests must be confirmed by detecting HCV RNA in blood by molecular amplification, most generally PCR. An EIA positive patient who is repeatedly negative by sensitive PCR for HCV RNA is considered to have either a resolved infection or a false-positive screening test. Either way, such patients are managed as if uninfected.
What Are the Safest and Most Effective Treatment Options?
Unfortunately, we cannot currently answer this question with confidence, given the limited data to guide us and the lack of serial liver biopsy studies (the gold standard) to reassure us that any form of therapy is totally safe. Many rheumatologists have suggested that conventional wisdom tells us that, given the absence of an obvious hepatotoxicity signal in the untold numbers of HCV-infected RA patients exposed to DMARD therapies, we should conclude that we are inflicting no obvious harm on our patients. Overinterpretation of such observations should be cautioned against, since the natural history of HCV infection extends over decades.
In the absence of biopsy data, at minimum, drugs with prominent hepatotoxic profiles such as methotrexate and leflunomide should be avoided in general. This is in accordance with the most recent ACR recommendations that suggest avoiding these DMARDs in all patients with chronic hepatitis C.14 Although this is a general statement, we believe that, in individual patients where there is a clear indication for treatment with these DMARDs, exceptions to these recommendations exist. Critical to the use of any DMARD in an HCV-infected patient with RA is the strong relationship between the rheumatologist, the patient, and the consulting hepatologist. We believe that, in a highly adherent patient, methotrexate or leflunomide can be started or continued if liver function is stable and there is no or minimal fibrosis in the liver biopsy.
