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

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).

Diagnostic Approach

• The European Association for the Study of the Liver (EASL) recommends that all patients with suspected chronic HCV infection should be tested for anti-HCV antibodies in serum or plasma as the first-line diagnostic test 1.
• If anti-HCV antibodies are detected, either HCV RNA or HCV core antigen should be determined to identify patients with ongoing infection 1.
• HCV core antigen detection can be used to diagnose viraemia in recently acquired HCV infection, in chronic infection, or after HCV reinfection, and is a suitable alternative when HCV RNA assays are not available or not affordable 1.

Test Characteristics

• HCV core antigen assays are less sensitive than HCV RNA assays for the diagnosis of viraemia, with a lower limit of detection equivalent to approximately 500 to 3,000 HCV RNA IU/ml, depending on the HCV genotype 1.
• HCV core antigen detection can be used as a surrogate marker of HCV replication, and can be used instead of HCV RNA to diagnose acute or chronic infection when HCV RNA assays are not available or not affordable 1.

Clinical Considerations

• In patients with suspected acute HCV infection, HCV RNA testing should be part of the initial evaluation, as HCV RNA typically becomes reliably detectable within 2–3 weeks after viral exposure 1.
• In patients with suspected chronic HCV infection, anti-HCV antibody testing is the first line diagnostic test, followed by HCV RNA or HCV core antigen testing if antibodies are detected 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.