What is the expected finding if Hepatitis C Virus (HCV) RNA is checked immediately at the end of an 8-week course of antiviral therapy?

Expected HCV RNA Findings at the End of 8-Week Antiviral Therapy

At the end of an 8-week course of antiviral therapy for hepatitis C virus (HCV), the expected finding is undetectable HCV RNA (<50 IU/mL), which is defined as an End of Treatment Response (ETR).

Understanding End of Treatment Response

The KASL clinical practice guidelines clearly define an End of Treatment Response (ETR) as undetectable HCV RNA at the end of treatment using a sensitive assay with a lower limit of detection <50 IU/mL 1. This is a critical milestone in HCV treatment that indicates the immediate effectiveness of the antiviral regimen.

Virological Response Patterns During HCV Treatment

HCV RNA levels typically follow a predictable pattern during antiviral therapy:

1. Rapid Virological Response (RVR): Undetectable HCV RNA at week 4 of therapy
2. Early Virological Response (EVR): ≥2 log reduction of HCV RNA level from baseline at week 12
3. End of Treatment Response (ETR): Undetectable HCV RNA at the end of treatment
4. Sustained Virological Response (SVR): Undetectable HCV RNA at 12 or 24 weeks after treatment completion

Importance of ETR Measurement

Measuring HCV RNA at the end of treatment is recommended by guidelines to evaluate therapeutic effects 1. However, it's important to note that:

• ETR alone does not guarantee a cure
• The gold standard for determining cure is SVR, measured at 12 or 24 weeks post-treatment
• Modern guidelines recommend HCV RNA testing at the end of treatment and 12 weeks after treatment cessation 1

Monitoring Recommendations

According to the AASLD-IDSA guidelines, quantitative HCV viral load testing:

• Is recommended after 4 weeks of therapy
• Can be considered at the end of treatment
• Is recommended at 12 weeks following completion of therapy 1

Clinical Implications

While achieving undetectable HCV RNA at the end of treatment is expected and desired, it's important to understand:

• Not a guarantee of SVR: Some patients with ETR may still relapse, defined as the reappearance of HCV RNA after treatment is discontinued 1
• Monitoring for relapse: The definitive determination of cure requires SVR12 or SVR24 testing
• High correlation with SVR: Most patients who achieve ETR will go on to achieve SVR, but follow-up testing is essential

Pitfalls and Caveats

• Assay sensitivity matters: Use a sensitive detection test with a lower detection threshold <15 IU/mL, ideally a real-time PCR test 1
• Interpretation challenges: Results showing HCV RNA below the threshold of quantification but still detectable can be problematic for clinical decision-making 1
• Laboratory delays: Consider potential delays in obtaining results when planning follow-up visits 1

Conclusion for Clinical Practice

When checking HCV RNA immediately at the end of an 8-week course of antiviral therapy, clinicians should expect to find undetectable levels (<50 IU/mL). However, this finding must be confirmed with SVR testing at 12 weeks post-treatment to establish cure.