Quantitative analysis of hepatitis C virus RNA: relationship between the replicative level and the various stages of the carrier states or the response to interferon therapy.

The authors quantified hepatitis C virus (HCV) RNA in serum by the competitive RT-PCR assay to correlate the replicative level of HCV with [1] various stages of the carrier states or [2] a sustained response to interferon therapy. The competitive RT-PCR assay employed is based on co-amplification of the target RNA with known amounts of synthetic mutated RNA having a novel restriction endonuclease (EcoRI) site. The titer of circulating HCV RNA defined as log10 (copy numbers/ml serum) were lower in asymptomatic blood donors (5.4 +/- 2.0) and in patients with chronic persistent hepatitis (7.3 +/- 1.1) compared with those having chronic active hepatitis (7.9 +/- 0.8), liver cirrhosis (7.8 +/- 0.7) and hepatocellular carcinoma (7.9 +/- 0.7). The initial titer of circulating HCV RNA of long-term responders before interferon therapy (7.1 +/- 1.2) was significantly lower than that of short-term responders (8.3 +/- 0.5) and non-responders (8.1 +/- 0.4). Multivariate multiple logistic regression showed that the titer of HCV RNA before therapy was the strongest independent predictor of a sustained response to interferon therapy. These results showed that the replicative level of hepatitis C virus is higher in advanced liver disease and that the replicative state of HCV is the most important factor influencing sustained response to interferon treatment.