The development of more sensitive HCV RNA assays might necessitate re-evaluation of the rules for stopping treatment (for example, HCV RNA negativity at week 24 during treatment with pegylated interferon-α and ribavirin for chronic hepatitis C). The aim of this study was to assess discordance between the week 24 HCV RNA test results of two PCR-based assays (Amplicor and Taq-Man) and the transcription-mediated amplification (TMA) HCV RNA qualitative assay.
Methods
A total of 89 week 24 samples that were negative using PCR-based assays during treatment were retested with the TMA qualitative assay to investigate discordance between tests results. All week 24 samples were HCV RNA negative by Amplicor or by TaqMan.
Results
Of the 89 patients, 46 (52%) achieved sustained virological response (SVR). Viral breakthrough or relapse occurred in 43 patients (48%). All 89 HCV RNA negative week 24 samples were retested with the qualitative TMA assay. Eleven out of 89 samples had detectable HCV RNA (12%). All patients with detectable HCV RNA experienced breakthrough or relapse (negative predictive value 100%). Of the 78 patients with undetectable HCV RNA at week 24 using the TMA assay, 46 achieved SVR. This resulted in a positive predictive value (PPV) of 59% for the TMA assay compared with a PPV of 52% for the PCR-based assays.
Conclusions
All patients with detectable HCV RNA at week 24 using the TMA assay eventually relapsed. On the basis of these results, the use of this more sensitive HCV RNA assay could lead to the prevention of unnecessary treatment.
References
1.
HadziyannisS.J., SetteH.Jr., MorganT.R.Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med2004; 140: 346–355.
2.
FriedM.W., ShiffmanM.L., ReddyK.R.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med2002; 347: 975–982.
3.
MannsM.P., McHutchisonJ.G., GordonS.C.Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet2001; 358: 958–965.
4.
FerenciP., FriedM.W., ShiffmanM.L.Predicting sustained virological responses in chronic hepatitis C patients treated with peginterferon alfa-2a (40 KD)/ ribavirin. J Hepatol2005; 43: 425–433.
5.
GhanyM.G., StraderD.B., ThomasD.L., SeeffL.B.; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology2009; 49: 1335–1374.
6.
PoynardT., MarcellinP., LeeS.S.Randomised trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. International Hepatitis Interventional Therapy Group (IHIT). Lancet1998; 352: 1426–1432.
7.
SarrazinC., HendricksD.A., SedaratiF., ZeuzemS.Assessment, by transcription-mediated amplification, of virologic response in patients with chronic hepatitis C virus treated with peginterferon alpha-2a. J Clin Microbiol2001; 39: 2850–2855.
8.
SarrazinC.Highly sensitive hepatitis C virus RNA detection methods: molecular backgrounds and clinical significance. J Clin Virol2002; 25Suppl 3: S23–S29.
9.
BarbeauJ.M., GoforthJ., CaliendoA.M., NolteF.S.Performance characteristics of a quantitative TaqMan hepatitis C virus RNA analyte-specific reagent. J Clin Microbiol2004; 42: 3739–3746.
10.
Martinot-PeignouxM., KhiriH., LeclereL., MaylinS., MarcellinP., HalfonP.Clinical performances of two real-time PCR assays and bDNA/TMA to early monitor treatment outcome in patients with chronic hepatitis C. J Clin Virol2009; 46: 216–221.
11.
GorrinG., FriesenhahnM., LinP.Performance evaluation of the VERSANT HCV RNA qualitative assay by using transcription-mediated amplification. J Clin Microbiol2003; 41: 310–317.
12.
RoomerR., HansenB.E., JanssenH.L., de KnegtR.J.Risk factors for infection during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. Hepatology2010; 52: 1225–1231.
13.
RoomerR., HansenB.E., JanssenH.L., de KnegtR.J.Thrombocytopenia and the risk of bleeding during treatment with peginterferon alfa and ribavirin for chronic hepatitis C. J Hepatol2010; 53: 455–459.
14.
ComanorL., AndersonF., GhanyM.Transcription-mediated amplification is more sensitive than conventional PCR-based assays for detecting residual serum HCV RNA at end of treatment. Am J Gastroenterol2001; 96: 2968–2972.
15.
SarrazinC., TeuberG., KokkaR., RabenauH., ZeuzemS.Detection of residual hepatitis C virus RNA by transcription-mediated amplification in patients with complete virologic response according to polymerase chain reaction-based assays. Hepatology2000; 32: 818–823.
16.
GerottoM., Dal PeroF., BortolettoG.Hepatitis C minimal residual viremia (MRV) detected by TMA at the end of Peg-IFN plus ribavirin therapy predicts post-treatment relapse. J Hepatol2006; 44: 83–87.
17.
DesombereI., Van VlierbergheH., CouventS., ClinckspoorF., Leroux-RoelsG.Comparison of qualitative (COBAS AMPLICOR HCV 2.0 versus VERSANT HCV RNA) and quantitative (COBAS AMPLICOR HCV monitor 2.0 versus VERSANT HCV RNA 3.0) assays for hepatitis C virus (HCV) RNA detection and quantification: impact on diagnosis and treatment of HCV infections. J Clin Microbiol2005; 43: 2590–2597.
18.
MorishimaC., MorganT.R., EverhartJ.E.HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial. Hepatology2006; 44: 360–367.
19.
MorishimaC., MorganT.R., EverhartJ.E.Interpretation of positive transcription-mediated amplification test results from polymerase chain reaction-negative samples obtained after treatment of chronic hepatitis C. Hepatology2008; 48: 1412–1419.
