In a dialysis patient with a positive hepatitis C virus (HCV) antibody screen (card test) but a negative ELISA, should HCV RNA PCR testing be performed?

HCV Testing in Dialysis Patients with Discordant Results

Yes, HCV RNA testing is absolutely necessary in this dialysis patient with a positive card test but negative ELISA. 1

Why HCV RNA Testing is Essential in This Case

Dialysis patients have a uniquely high rate of false-negative antibody tests and occult HCV infection that makes RNA testing mandatory when any screening test is positive. 1, 2

Critical Evidence from Dialysis Populations

• Up to 28% of hemodialysis patients who are HCV antibody-negative have detectable HCV RNA by PCR, representing true active infection that would be missed by antibody testing alone 2
• In dialysis units with high HCV prevalence, initial testing with nucleic acid testing (NAT) should be considered rather than relying on antibody assays 1
• The immunosuppressed state of dialysis patients creates a prolonged window period where HCV RNA is positive but antibodies remain negative or equivocal 3, 4

KDIGO 2022 Guideline Recommendations

The most authoritative guidance comes from the KDIGO 2022 Clinical Practice Guideline, which provides two acceptable screening strategies for dialysis patients 1:

1. NAT (HCV RNA) alone (Grade 1A recommendation)
2. Immunoassay followed by NAT if immunoassay is positive (Grade 1A recommendation)

Your patient falls into the second category—any positive screening test (including the card test) mandates confirmatory HCV RNA testing. 1

Understanding the Discordant Results

The positive card test followed by negative ELISA creates diagnostic uncertainty that can only be resolved by RNA testing 1:

• Different antibody assays use different antigens and platforms, so discordant results between tests are not uncommon 5, 6
• The card test may have detected early antibody formation that the ELISA missed, or vice versa 1, 4
• False-negative ELISA results occur in 10% of dialysis patients with active HCV infection due to immunosuppression, uremia, or technical factors 1, 2

Practical Testing Protocol

Draw blood for HCV RNA testing BEFORE the dialysis session, as hemodialysis reduces viremia levels and can produce falsely low or negative results 1:

• Use a quantitative HCV RNA assay with a detection limit ≤25 IU/mL 1
• If HCV RNA is positive, proceed with genotype testing and liver disease staging 7
• If HCV RNA is negative, repeat testing in 3 months given the discordant antibody results and ongoing dialysis exposure risk 1

High-Risk Context of Dialysis

This patient requires RNA testing because dialysis patients represent a uniquely high-risk population 1:

• HCV prevalence in hemodialysis patients is significantly higher than the general population 1
• Patient-to-patient transmission occurs repeatedly in dialysis centers despite infection control measures 1
• Any new HCV infection must be reported to public health authorities and triggers facility-wide screening 1

Common Pitfalls to Avoid

• Never rely on a single antibody test (positive or negative) to diagnose or exclude HCV in dialysis patients 1, 2
• Do not assume a negative ELISA rules out infection when another screening test is positive 1, 2
• Do not delay RNA testing while repeating antibody assays—proceed directly to molecular testing 1, 3
• Remember that antibody tests cannot distinguish active infection from resolved infection—only HCV RNA confirms current viremia 1, 5

Alternative: HCV Core Antigen Testing

If HCV RNA testing is unavailable or cost-prohibitive, HCV core antigen assay is an acceptable alternative with 84-89% sensitivity and specificity in dialysis populations 8, 4, 9:

• Core antigen testing is less expensive than PCR but more sensitive than antibody testing alone 8
• It can detect infection during the window period when antibodies are absent 4, 9
• However, it has a higher detection threshold (150-3000 IU/mL) than RNA testing and may miss low-level viremia 1

The definitive answer: Proceed immediately with HCV RNA testing drawn before dialysis to confirm or exclude active infection in this patient with discordant antibody results. 1