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1 September 1995 | Volume 123 Issue 5 | Pages 321-329
Objective: To compare two recently developed molecular techniques for quantitating the levels of hepatitis C virus (HCV) RNA in the serum of patients with a wide spectrum of chronic hepatitis C.
Design: Serum samples from 299 patients with HCV viremia, 101 control patients without HCV infection, and 19 consecutive patients receiving systemic interferon therapy were evaluated by a commercially available branched-chain DNA (bDNA) assay and a quantitative competitive polymerase chain reaction (PCR).
Setting: University-based hepatology clinics and reference virology laboratory.
Patients: Patients with HCV viremia as defined by results of qualitative RNA PCR, including 53 HCV-infected blood donors, 34 patients receiving renal dialysis, and 212 patients attending a hepatology clinic.
Results: Results of in vitro and in vivo experiments indicated that the sensitivity and dynamic range of the PCR assays were greater than those of the bDNA assay. Detection of HCV viremia by the bDNA assay was highly dependent on viral RNA titers, with a sensitivity of 5% at HCV RNA titers of 5.0 logs per mL or less and 94% at titers of 5.5 logs per mL or greater. The best correlation between assays was observed in specimens with HCV RNA titers between 6.0 and 7.5 logs per mL (r = 0.73). In patients with high-titer HCV viremia, including liver transplant recipients and patients with cirrhosis, quantitative PCR results were an average of 12-fold higher than bDNA assay results. Results of repetitive testing of discordant specimens showed that these discrepancies were caused by a high kit-to-kit coefficient of variation (112%) in the bDNA assay. Of 19 patients receiving interferon therapy, 9 (47%) became bDNA negative, but only 5 became quantitative PCR negative. The bDNA-negative, quantitative PCR-positive patients all had relapse when therapy was discontinued.
Conclusions: The bDNA assay has a narrower linear range for quantitation of HCV viremia than quantitative PCR. Because persons with low HCV titers may respond well to therapy, seropositive persons with negative bDNA results should be retested with PCR-based assays. Similarly, the bDNA assay may underestimate the true degree of HCV viremia in persons with endstage infection (> 107 RNA equivalents/mL of sera). Despite these limitations, the combination of bDNA- and PCR-based assays appears to be optimal for selecting and following patients during interferon therapy.
Author and Article Information
From the University of Washington Medical Center and Harborview Medical Center, Seattle, Washington.
ARTICLE
Assessment of Hepatitis C Viremia Using Molecular Amplification Technologies: Correlations and Clinical Implications
Acknowledgments: The authors thank Dr. James Perkins of the University of Washington Medical Center, Dr. Merlin Sayers of Puget Sound Blood Center, Dr. Michael Busch of Irwin Memorial Blood Centers, and Dr. Christopher Blagg of the Northwest Kidney Foundation for ongoing collaboration and for providing some of the clinical specimens used in the current study, and Ms. Willa Lee and Ms. Minjun Chung for technical assistance.
Requests for Reprints: David Gretch, MD, PhD, Virology Division, 9th Floor, Pacific Medical Center, 1200 12th Avenue South, Seattle, WA 98144.
Current Author Addresses: Drs. Gretch, Williams, and Corey: Virology Division, 9th Floor, Pacific Medical Center, 1200 12th Avenue South, Seattle, WA 98144.
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