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 alpha 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 alpha and interleukin 6.


CONCLUSIONS
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.
Kalantar-Zadeh
Kamyar
K
Division of Nephrology and Hypertension, Los Angeles Biomedical Institute, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. Kamka@ucla.edu
Miller
Loren G
LG
Daar
Eric S
ES
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002100:Cachexia / Q000097:blood / Q000150:complications; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D005188:False Negative Reactions; D005260:Female; D005784:Gene Amplification; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000175:diagnosis*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D034141:Hypoalbuminemia / Q000209:etiology; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000097:blood; D007501:Iron / Q000097:blood; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011502:Protein-Energy Malnutrition / Q000097:blood / Q000150:complications; D012367:RNA, Viral / Q000032:analysis*; D006435:Renal Dialysis; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018937:Hepatitis C Antibodies; D015850:Interleukin-6; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase