Test ID: QHCV    
Hepatitis C Virus RNA Quantification by bDNA, Serum

Quantification of hepatitis C virus (HCV) RNA levels in serum of patients with confirmed chronic HCV infection (known to have detectable HCV RNA in serum)

Monitoring progression of chronic HCV infection and responses to anti-HCV therapy

Hepatitis C virus (HCV) is the most common cause of viral hepatitis in the western hemisphere. In the United States, approximately 2.7 million people are estimated to have chronic HCV infection, which may progress to cirrhosis and, in some patients, hepatocellular carcinoma.

In patients with chronic HCV infection, a favorable response to interferon-alpha and ribavirin combination therapy is associated with low pretreatment (ie, baseline) serum or plasma HCV RNA levels, absence of cirrhosis or significant fibrosis, and HCV genotype 2 or 3. Recent clinical trial studies suggested that responders to anti-HCV therapy have a more rapid fall in serum HCV RNA levels (>2 log decrease from baseline level) by the fourth week of treatment (rapid virologic response) than nonresponders. Serum or plasma HCV RNA level at 12 weeks of therapy (early virologic response) is also useful for predicting sustained virologic response to treatment.

<615 IU/mL

This assay has a quantification range of 615 to 7,690,000 IU/mL (2.79-6.89 log IU/mL). Results are reported as integers in IU/mL (rounded to 3 significant figures) and log IU/mL.

A result of <615 IU/mL indicates that either the specimen contains no detectable hepatitis C virus (HCV) RNA or the HCV RNA level is below the lower limit of quantification for this assay.

A result of >7,690,000 IU/mL indicates that the HCV RNA level is above the upper limit of quantification for this assay.

Due to the potential for false-positive results, this assay should not be used for initial detection of hepatitis C virus (HCV) RNA in patients with suspected acute or chronic HCV infection. It should be used to quantify HCV RNA in patients who have been found to be positive by a more sensitive HCV RNA detection or quantification assay.

A result of <615 IU/mL (<2.79 log IU/mL) does not rule out the presence of HCV RNA in the specimen.

The lower limit of quantification was 615 IU/mL (the lowest quantifiable hepatitis C virus (HCV) RNA level that shows <35% coefficient of variation, %CV, and within 0.1 log IU/mL from the linearized expected level). Total %CV ranged from 9.9% to 26.3% for analytical standards with HCV RNA levels within the quantification range of this assay. There was very good correlation (r=1.0) between the observed and linearized expected mean values of HCV RNA levels ranging from 615 to 7,360,623 IU/mL.

Of the 302 serum or EDTA-plasma specimens collected from healthy blood donors and tested, 300 showed HCV RNA levels of <615 IU/mL, yielding an analytical specificity of 99.3% (lower 95% confidence limit at 97.9%).

Deming regression analysis of paired results on 57 serum specimens tested by this assay using the Versant 440 Molecular System and S340 bDNA System showed good correlation (r = 0.997) between the 2 assays with the regression equation, y = 0.934x + 0.383. The mean difference in HCV RNA levels obtained between the 2 assays was 0.05 log IU/mL, with the differences ranging from -0.11 to 0.38 log IU/mL, and 96.5% (55 of 57 specimens) of these differences were within  0.17 log IU/mL ( 1.96 SD) from the mean difference. HCV RNA results obtained by the Versant 440 System were higher than those obtained by the S340 bDNA System at HCV RNA levels of <5.0 log IU/mL and lower at HCV RNA levels of >5.0 log IU/mL.

1. Pawlotsky JM: Use and interpretation of hepatitis C virus diagnostic assays. Clin Liver Dis 2003;7:127-137

2. Strader DB, Wright T, Thomas DL, Seeff, LB: Diagnosis, management and treatment of hepatitis C. Hepatology 2004;39:1147-1171

3. Chevaliez S, Pawlotsky JM: Use of virologic assays in the diagnosis and management of hepatitis C virus infection. Clin Liver Dis 2005;9(3):371-382