Intermittent Viremia in Acute Hepatitis C
Intermittent viremia is unusual in untreated patients with acute hepatitis C, though brief periods of low-level or undetectable HCV RNA can occur during the early incubation phase before exponential viral replication begins. 1
Frequency and Patterns
In established acute HCV infection, intermittent viremia is uncommon - the 2001 Gut guidelines explicitly state that "intermittent viraemia is unusual in patients untreated with IFN," enhancing the significance of a negative PCR result 1
However, during the very early pre-ramp-up phase of acute infection, intermittent low-level viremia can occur for up to 2 months before exponential viral growth begins - one study documented intermittent viremia in 37 of 50 panels, with the earliest detectable viremic bleed occurring 63 days before the estimated onset of exponential viral replication 2
Once the ramp-up phase begins, viral load doubles every 10.8 hours and progresses to a sustained high-titer plateau phase lasting approximately 56 days before seroconversion 2
Clinical Implications for Diagnosis
About 50% of patients with acute hepatitis C will be anti-HCV positive at initial presentation, meaning antibodies may not yet be detectable when symptoms first appear 1, 3
HCV RNA testing should be part of the initial evaluation when acute hepatitis C is suspected, particularly in immunocompromised patients or those with recent exposure, since antibody tests may be negative early in infection 1, 4
A single negative HCV RNA result can be difficult to interpret in the context of suspected acute infection - it could represent the pre-ramp-up intermittent viremia phase, a level below assay detection limits, or true absence of infection 1
If HCV RNA is negative but clinical suspicion remains high, repeat HCV RNA testing should be performed - the CDC recommends retesting anti-HCV positive, HCV RNA negative individuals 3 months later to confirm recovered infection 1
Important Caveats
The intermittent viremia pattern described in early acute infection differs fundamentally from the situation in chronic HCV, where persistent viremia is the norm and intermittent viremia would be highly unusual 1
Brief periods of undetectable HCV RNA may occur even during acute infection, but this represents transient fluctuations rather than true intermittent viremia once exponential replication has begun 1
In special populations like hemodialysis patients with chronic HCV, approximately 33% demonstrate intermittent viremia patterns, but this is distinct from the acute infection scenario 5
Practical Testing Approach
Use sensitive molecular methods with lower limit of detection <15 IU/ml for HCV RNA testing 1, 3
For suspected acute HCV with negative initial HCV RNA, consider repeat testing in 2-4 weeks to capture the transition from intermittent low-level viremia to sustained high-titer viremia 4
Do not rely solely on antibody testing in suspected acute infection - approximately 50% will be antibody-negative at presentation 1, 3