We acknowledge the comments of Moreau et al. on our recent article.1 They argue that subjects who were positive for hepatitis C virus (HCV) RNA by polymerase chain reaction analysis on a single occasion over several years follow-up may have very low level viral replication at the limits of detection.2 We agree; certainly there have been technical improvements since some of these samples were assayed up to 16 years ago. They also point out that “recrudescence” of hepatitis C virus replication has never been observed in the Irish cohort infected by contaminated anti-D immune globulin. We cannot be certain whether the four patients in our series who persistently became RNA positive represented reinfection or recrudescence. However, the Irish and Cambridge cohorts acquired HCV by different routes and are not comparable.
We feel however, that Moreau and colleagues have missed the point behind the submission. Regardless of interpretation of HCV RNA results in those nine individuals (and we stand by our original interpretation), there remain 56 in a series of 61 patients (culled from a much larger cohort) with an abnormal liver biopsy that could not be explained by other aetiology and in whom the pattern of inflammation was indistinguishable from that in hepatitis C viremic cases with a similar stage of fibrosis.
If the purpose of the publication had been to examine the accuracy of HCV RNA testing then we agree that further molecular analysis would have been helpful. We elected not to pursue this approach because of the age, storage conditions and availability of the serum samples in question.
We also agree that identification of positive and negative strand HCV RNA from liver tissue would have been ideal, but that would have needed a great deal of foresight in the period 1992-2000. Again, we stand by our original interpretation that an inflammatory response in the liver may be the most sensitive measure of HCV replication in situ.