Detection of low amounts of HCV-RNA in the serum of sustained virological responders after antiviral therapy

Aims: As new, more sensitive methods for the detection and quantification of the hepatitis C virus are becoming available, a careful clinical interpretation of the results is needed.

Methods: In order to evaluate a new commercial HCV quantification assay with a lower detection limit (Abbott m2000 real-time PCR system), we performed serial logarithmic dilutions of serum from genotypes 1–6 starting from a 10⁶ virus load.

Consequently we tested sera of 50 patients with chronic hepatitis C infection after treatment with PEG-IFNa + Ribavirin between 2001 and 2004. All patients had a Sustained Virological Response (HCV-RNA negative by Cobas Amplicor^TM six months after therapy end). Sera at least 6 months after the end of treatment, stored at –20°C, were re-tested with the Abbott HCV RealTime PCR.

Results: The method was stable providing a linear decline of the virus load of the dilutions in all genotypes until the area of 12 IU/ml.

From the 50 patients that were examined, 9 had detectable but not quantifiable HCV-RNA (<12 IU/ml) and two had a viral load <100 IU/ml. Interestingly, the one of these two patients had a persisting light increase of the liver enzymes since a successful antiviral treatment five years ago and has always tested RNA negative with the conventional methods until today.

Conclusion: The meaning of the detection of low viral load in patients after antiviral therapy for chronic hepatitis C with the new highly sensitive methods is controversial. It may be associated with a mild course of liver inflammation in single cases, but in most patients it does not show to have a clinical implication. Bigger and longer-term studies of patient cohorts after treatment should evaluate the meaning of low persisting viraemia.