Assessment of early virological response to antiviral therapy by comparing four assays for HCV RNA quantitation using the international unit standard: Implications for clinical management of patients with chronic hepatitis C virus infection

Abstract

WHO International Standards for nucleic acid tests are used widely to compare the different assays used in HCV RNA quantitation. The aim of the study was to assess the impact of the international unit standard for measuring HCV RNA in the management of patients with chronic hepatitis C virus (HCV) infection. Twenty-seven naïve patients infected chronically by HCV were treated with ribavirin plus PEG-interferon-alfa-2b for 48 weeks. SVR was obtained for 16 patients (the other were non-responders). For HCV RNA quantitation, four assays were undertaken: Versant HCV RNA 3.0 (Bayer), Real time PCR (TaqMan, Roche), LCx HCV RNA (Abbott), and Cobas Amplicor-Monitor v2 (Roche). Considering a 2-log decline at Week 12 after the beginning of therapy, discordant results were found with the four HCV RNA methods in predicting SVR or non-response. At Week 4 and Week 12, significant differences were observed between Versant HCV RNA 3.0 versus PCR HCV Taqman, Versant HCV RNA 3.0 versus LCx HCV RNA, Cobas Monitor Amplicor HCV 2.0 versus LCx HCV RNA, and Cobas Monitor Amplicor HCV 2.0 versus PCR HCV Taqman (P < 0.001). The HCV RNA cutoff, given a 100% negative predictive value at Week 4 and Week 12, differed with the assays used to quantify HCV RNA, despite the use of the IU/ml units. Eighty-nine percent of serum values for HCV RNA were concordant by the IU standard. All assays, however, failed to detect HCV RNA in some cases. Despite the use of the IU standard HCV-infected patients might be monitored with only one assay.

Real-Time PCR Assays for Hepatitis C Virus (HCV) RNA Quantitation Are Adequate for Clinical Management of Patients with Chronic HCV Infection

“…In a recent comparative study (11), we demonstrated that the absolute values obtained with these assays are different and that the HCV RNA viral load decline, assessed by different assays during antiviral therapy, can give different results regardless of the use of international units.…”

“…In a previous study, false-positive and false-negative results, as well as variations in the HCV RNA level of Ͼ1 to 2 log IU, were observed. These results may have an impact on the management of patients receiving interferon therapy, for example, when treatment decisions are made using a single HCV RNA determination (11). Two standardized HCV RNA quantitative assays based on real-time PCR were recently developed (Abbott RealTime HCV and Roche Cobas TaqMan HCV).…”

Evaluation of the Abbott Investigational Use Only RealTi m e Hepatitis C Virus (HCV) Assay and Comparison to the Roche TaqMan HCV Analyte-Specific Reagent Assay

“…Third, while the introduction of an international standard has greatly improved the ability to compare results from different laboratories, there are still two problems. Studies have shown that even when assays are calibrated to the same international standard, results from different assays cannot be reliably compared (3,5,7). Finally, the international standard represents a single instance of a genotype 1 specimen.…”

Determinazione quantitativa di HCV-RNA: valutazione comparativa dei saggi Abbott Real-Time e Versant bDNA v.3

“…I valori di HCV-RNA rilevati prima e durante il trattamento di combinazione con interferone pegilato e ribavirina costituiscono parametri indispensabili per indirizzare la decisione terapeutica, in particolare nei pazienti con infezione da genotipi 1, 4 e 6 (6,9,11). In questi soggetti livelli basali di viremia maggiori di 30.000 UI/mL ed una riduzione dei valori riscontarti dopo 12 settimane di trattamento inferiore a 2 log rispetto ai valori iniziali sono considerati predittivi di fallimento virologico e costituiscono una indicazione ad interrompere precocemente la terapia (13,24,26).…”