What diagnostic test should be used for a patient with Hepatitis C (HCV) infection in the absence of viral Ribonucleic Acid (RNA)?

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From the Guidelines

HCV core antigen testing is the recommended diagnostic test for a patient with Hepatitis C (HCV) infection in the absence of viral Ribonucleic Acid (RNA).

Rationale

  • The European Association for the Study of the Liver (EASL) recommends that HCV core antigen detection can be used to diagnose viraemia in recently acquired HCV infection, in chronic infection, or after HCV reinfection 1.
  • HCV core antigen assays are less sensitive than HCV RNA assays for the diagnosis of viraemia, but can be used when HCV RNA assays are not available or not affordable 1.
  • The American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) recommend HCV-antibody and HCV-RNA testing when acute HCV infection is suspected, but HCV core antigen testing can be used as an alternative when HCV RNA is not detectable 1.
  • HCV core antigen testing is a useful tool for diagnosing HCV infection, especially in resource-limited settings where HCV RNA testing may not be available 1.

Key Points

  • HCV core antigen testing can be used to diagnose HCV infection in the absence of viral RNA.
  • HCV core antigen assays are less sensitive than HCV RNA assays, but can be used as an alternative when HCV RNA is not detectable.
  • Reflex testing, which involves testing for HCV RNA in the sample obtained for anti-HCV antibody testing, can substantially increase the proportion of anti-HCV antibody-positive patients who are tested for viraemia and receive subsequent linkage to care 1.

From the Research

Diagnostic Tests for HCV Infection

In the absence of viral Ribonucleic Acid (RNA), the following diagnostic tests can be used for a patient with Hepatitis C (HCV) infection:

  • HCV core antigen testing: This test can be used as an alternative to HCV-RNA detection, as it is easy to operate, time-saving, and low-cost 2. HCV core antigen can be detected within 12-15 days after infection and can distinguish between previous and current infection 2.
  • Anti-HCV antibody testing: This test can be used for screening, but it does not discriminate between active and past infection 3, 4.
  • Combination of HCV core antigen and antibody serology: This combination can help detect HCV infection earlier, accurately diagnose different stages of HCV infection, and evaluate the therapeutic effect of antiviral drugs 2, 4.

Advantages and Limitations of HCV Core Antigen Testing

The advantages of HCV core antigen testing include:

  • High consistency with HCV-RNA expression 2
  • Easy to operate, time-saving, and low-cost 2
  • Can distinguish between previous and current infection 2
  • Can be used to monitor antiviral efficacy and predict sustained virological response (SVR) 2 The limitations of HCV core antigen testing include:
  • Lower sensitivity compared to HCV RNA assays 3, 4
  • May not be suitable for all patient populations, such as immunocompromised individuals 3

Clinical Application of HCV Core Antigen Testing

HCV core antigen testing can be used as a confirmatory test for HCV antibody-positive, therapy-naive individuals 5. It can also be used to monitor treatment response and predict SVR 2, 4. However, more data are needed to fully establish its role in treatment monitoring 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Evaluation of in vitro screening and diagnostic kits for hepatitis C virus infection.

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 2018

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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