Can Hepatitis C Virus (HCV) RNA be undetectable but have a viral load titre of 100,000 (one lac)?

HCV RNA Cannot Be Both Undetectable and Have a Titre of 100,000 IU/mL

It is not possible for HCV RNA to be simultaneously undetectable and have a viral load of 100,000 (one lac) IU/mL. These are contradictory findings as "undetectable" means the virus cannot be detected by the assay, while a specific numerical value indicates a quantifiable amount of virus is present 1.

Understanding HCV RNA Testing and Terminology

HCV RNA testing involves several key concepts:

1. Detection threshold: Modern sensitive assays typically have lower limits of detection around 10-15 IU/mL 1
2. Quantification threshold: Most assays have a lower limit of quantification (LLOQ) of 12-25 IU/mL 1, 2
3. Testing terminology:
   • Undetectable: No HCV RNA detected (below the limit of detection)
   • Detectable but not quantifiable (DNQ): HCV RNA is detected but below the quantification threshold
   • Quantifiable: HCV RNA is present at levels that can be measured numerically

Why This Discrepancy Cannot Occur

There are several reasons why HCV RNA cannot be both undetectable and have a titre of 100,000 IU/mL:

1. Definition conflict: By definition, "undetectable" means the viral load is below the detection limit of the assay (typically <15 IU/mL) 1

2. Quantification range: A value of 100,000 IU/mL is well above the detection and quantification thresholds of all modern HCV RNA assays 1

3. Testing standards: Guidelines recommend using sensitive real-time PCR tests with low detection thresholds (≤25 IU/mL) for monitoring HCV treatment 1

Possible Explanations for Such a Discrepancy

If faced with such contradictory results, consider:

1. Laboratory error: Sample mix-up, reporting error, or transcription mistake

2. Different assays: Different testing methods can yield varying results. Studies show discordance between assays like COBAS TaqMan and Abbott RealTime, though not to this extreme magnitude 3, 2

3. Timing difference: Results might be from different time points during treatment

4. Misinterpretation: Confusion between "detected below quantification limit" (DNQ) and "undetectable" 4

Clinical Implications

The distinction between undetectable and detectable HCV RNA is crucial for:

1. Treatment decisions: Response-guided therapy depends on accurate viral load measurements 1

2. Stopping rules: Treatment discontinuation decisions are based on specific HCV RNA thresholds 1

3. SVR prediction: The likelihood of sustained virological response (SVR) correlates with the time to HCV RNA disappearance 1

Recommendations for Accurate HCV RNA Assessment

1. Use standardized testing: Employ sensitive detection tests with lower detection thresholds <15 IU/mL, ideally real-time PCR tests 1

2. Consistent methodology: Use the same assay throughout treatment monitoring 1

3. Regular monitoring: Measure viral load at appropriate intervals as recommended by guidelines 1

4. Proper interpretation: Understand the difference between undetectable, detectable but not quantifiable, and quantifiable results 1

If faced with contradictory results like this, repeat testing is warranted to resolve the discrepancy before making clinical decisions.