What is the confirmatory test for Hepatitis C (HCV) infection?

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From the Guidelines

The confirmatory test for hepatitis C is the HCV RNA test, which detects viral genetic material in the blood. This test is typically performed after a positive hepatitis C antibody screening test to confirm active infection. The HCV RNA test uses polymerase chain reaction (PCR) or other nucleic acid amplification techniques to directly detect the virus. A positive result indicates active infection, while a negative result after a positive antibody test suggests either past infection that has resolved or a false-positive antibody test. Additionally, the HCV RNA test can quantify viral load, which helps monitor treatment response. Genotype testing may follow confirmation to determine the specific strain of HCV, which guides treatment decisions. These molecular tests are highly accurate and can detect the virus even before antibodies develop, making them essential for early diagnosis and effective management of hepatitis C 1.

Some key points to consider when interpreting HCV RNA test results include:

  • A positive HCV RNA test result indicates active infection
  • A negative HCV RNA test result after a positive antibody test suggests either past infection that has resolved or a false-positive antibody test
  • Quantitative HCV RNA testing is recommended prior to initiation of antiviral therapy to document the baseline level of viremia
  • HCV genotype testing may be considered for those in whom it may alter treatment recommendations 1.

It's also important to note that the HCV RNA test can be used to detect reinfection after previous spontaneous or treatment-related viral clearance, as HCV-antibody positivity is expected in these cases 1.

In terms of screening and follow-up, HCV-antibody testing with reflex HCV RNA polymerase chain reaction testing is recommended for initial HCV screening, and quantitative HCV-RNA testing is recommended prior to initiation of antiviral therapy 1.

Overall, the HCV RNA test is a crucial tool in the diagnosis and management of hepatitis C, and its use is supported by the latest clinical guidelines 1.

From the Research

Confirmatory Tests for Hepatitis C (HCV) Infection

The confirmatory tests for HCV infection are necessary to exclude false-positive results, especially in low-prevalence populations. The following are the confirmatory tests used:

  • Qualitative polymerase chain reaction (PCR) assay for HCV RNA, which is the most appropriate test for confirming active infection 2, 3, 4, 5
  • Recombinant immunoblot assay (RIBA) for anti-HCV, which is used as a supplemental test to resolve false-positive results by enzyme immunoassay (EIA) 2, 4
  • Nucleic acid amplification tests (NAT) are used as confirmatory tools and to determine viral load prior to initiating treatment 6

Choosing the Appropriate Confirmatory Test

The choice of confirmatory test depends on the clinical setting and the likelihood of a true-positive EIA result. In general, confirmatory tests are unnecessary in anti-HCV-positive patients who present with chronic liver disease. However, in certain situations, such as in anti-HCV-positive blood donors and individuals with normal aminotransferase levels, confirmatory tests should always be performed 2.

Interpretation of Test Results

The interpretation of test results is crucial in diagnosing and managing HCV infection. The mainstay in diagnosing infection with HCV is to initially screen high-risk groups for antibodies to HCV (anti-HCV). The inclusion of serum to cut-off ratio (S/CO) in recent guidelines is helpful in deciding the supplemental assay to be used to confirm initially reactive screening results 6. A sensitive nucleic acid test should be used to confirm all cases of acute or chronic HCV infection, and a genotype test and quantitative HCV RNA test should be performed on all patients prior to therapy to best assess probability of response and to aid in selection of appropriate therapeutic regimen 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Diagnosis of hepatitis C.

Hepatology (Baltimore, Md.), 1997

Research

Hepatitis C virus diagnosis and testing.

Canadian journal of public health = Revue canadienne de sante publique, 2000

Research

Diagnostic tests for hepatitis C.

Hepatology (Baltimore, Md.), 1997

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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