Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy.

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95-0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7-5.0; P < 0.01), absence of HIV co-infection (OR: 2.08; 95% CI = 1.2-3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2-2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0-2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1-3.8; P = 0.03). In conclusion, among difficult-to-treat genotypes, the subtype 1a is associated with a lower response to anti-HCV therapy than subtypes 1b, 4a, and 4d.

Multicenter trials need to use the same assay for hepatitis C virus viral load determination.

This study, involving 20 laboratories and using currently available assays for hepatitis C virus RNA quantification, demonstrated that differences in viral load values are due not to interlaboratory variations but rather to the nature of the assay itself. This underlines the importance of using the same assay in multicenter studies or when monitoring antiviral therapy.

Expertise of French laboratories in detection, genotyping, and quantification of hepatitis C virus RNA in serum.

Before initiating new large-scale therapeutic trials for hepatitis C virus (HCV)-infected patients, the French Health Authorities for HCV research decided to organize an evaluation of the expertise of laboratories that could be engaged to undertake molecular biology assays in such trials; 21 experienced laboratories participated in this national evaluation of laboratory expertise, which was performed in two successive rounds. The first round evaluated the laboratories for their abilities to detect HCV RNA in serum, determine genotypes, and quantify HCV RNA loads. The results observed by qualitative assays for HCV RNA detection were 100% sensitivity and 100% specificity for all laboratories. The genotyping results were 100% concordant for 9 laboratories and greater than 90% for 10 laboratories. By contrast, large coefficients of variation were observed for quantitative determination of HCV RNA loads, leading to a second round with standardized quantitative assays only. The dispersion of the results was larger by the AMPLICOR HCV Monitor assay than by the branched-DNA assay (mean coefficients of variation, 57.4 and 16.9%, respectively). In the majority of cases, discrepancies between the results of the two tests were found for samples with high viral loads. These results indicate the usefulness of validating, by controlling for expertise, both the reliabilities of laboratories involved in multicenter work and the standardized assays chosen for use in the evaluation of the biological impacts of new therapies.