Diagnostic Discordance for Hepatitis C Virus Infection in Hemodialysis Patients

Background: Hepatitis C virus (HCV) infection is associated with an increase in proinflammatory cytokine levels. Similar changes are seen in maintenance hemodialysis patients with malnutrition-inflammation-cachexia syndrome (MICS), which is associated with poor clinical outcomes in this population. We hypothesized that HCV transcription-mediated amplification (TMA), a sensitive qualitative molecular test for HCV RNA, may identify maintenance hemodialysis patients with HCV infection not detected by means of antibody enzyme immunoassay (EIA), particularly in those with MICS. Methods: We evaluated HCV status in 314 maintenance hemodialysis patients by using HCV antibody EIA (version 2.0; Abbott Laboratories, Abbott Park, IL) and HCV TMA (Bayer Diagnostics Laboratories, Berkeley, CA). Results: Twenty-five patients (8%) were EIA positive (EIA+)/TMA+; 4 patients (1%), EIA+/TMA negative (TMA−), and 22 patients (7%), EIA−/TMA+. In the 47 TMA+ patients, the sensitivity of EIA for HCV infection was only 53%. TMA+ patients had lower albumin levels and higher tumor necrosis factor α and serum glutamic oxaloacetic transaminase levels than TMA− patients. EIA+/TMA+ patients were more likely than EIA−/TMA+ or EIA−/TMA− patients to have hypoalbuminemia and higher iron and transaminase levels. Of all TMA+ patients, EIA− patients were more likely to have diabetes, be on dialysis therapy longer, and have lower liver enzyme levels and higher proinflammatory cytokine levels, including tumor necrosis factor α and interleukin 6. Conclusion: Maintenance hemodialysis patients infected with HCV according to TMA have clinical features suggestive of MICS. In this population, HCV EIA appears to have a low sensitivity for the identification of HCV infection, which may be caused by the confounding effect of MICS or other demographic or clinical factors. These apparently false-negative HCV antibody test results are seen in persons with a longer time on hemodialysis therapy, mirroring observations in other populations with serious progressive conditions, such as human immunodeficiency virus infection.