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To the Editor:

The article by Martinot-Peignoux and colleagues1 nicely demonstrates that testing for serum hepatitis C virus (HCV) RNA with the highly sensitive transcription-mediated amplification assay [lower limit of detection (LOD) = 9.6 IU/mL] 12 weeks after the end of a treatment period with pegylated interferon (PegIFN) and ribavirin (Rbv) is as effective as the standard 24-week posttreatment completion measurement for assessing sustained virological response (SVR) in patients with chronic hepatitis C. Although we acknowledge that anticipating the response to therapy is likely to positively affect the management of HCV patients, we think that it is important to externally validate these results even with less sensitive commercially available HCV RNA assays. To answer this question, we analyzed two cohorts of consecutively treated naïve patients with chronic hepatitis C in whom different HCV RNA assays were used to determine the viral response during treatment and follow-up. The first cohort, consisting of 431 patients of any HCV genotype treated with either PegIFN-alfa2a/Rbv or PegIFN-alfa2b/Rbv (Milan Safety Tolerability study),2 was tested during and after treatment with a qualitative HCV RNA assay with a lower LOD of 50 IU/mL (COBAS Amplicor HCV test version 2.0, Roche Diagnostics).3 The second cohort consisted of 72 HCV-1 and HCV-4 patients who were consecutively treated with PegIFN-alfa2a/Rbv and evaluated with a real-time polymerase chain reaction assay with an LOD of 15 IU/mL (COBAS TaqMan 2.0, Roche Diagnostics).4 Both cohorts were followed up for at least 12 months after treatment completion, and they showed no hepatitis relapse after the achievement of SVR by the 24-week posttreatment time point, the SVR rates being 60% and 44%, respectively. With both assays, undetectable HCV RNA during week 12 of the posttreatment follow-up had a 100% positive predictive value (PPV) for SVR, with 95% confidence intervals (CIs) that very closely mimicked those reported by Martinot-Peignoux et al. in their study (Table 1). In our experience, during week 12 of follow-up, HCV RNA testing using assays less sensitive than the one used by Martinot-Peignoux and colleagues provided reliable estimates of SVR to PegIFN/Rbv therapy in naïve patients. Whether this holds true also for the retreatment of patients who have failed a previous course of interferon-based therapy remains to be established.

Table 1. Serum HCV RNA Outcome During the 24 Weeks Posttreatment Follow Up
Serum HCV RNA (Follow-Up)Patients (n)HCV RNA(−)SVRPPV (95% CI)
Amplicor (LOD = 50 IU/mL)431   
 Week 4 28525991% (86.9%-93.9%)
 Week 12 259259100% (98.6%-100%)
 Week 24 259259100% (98.6%-100%)
TaqMan (LOD = 15 IU/mL)72   
 Week 4 383284% (69%-94%)
 Week 12 3232100% (89%-100%)
 Week 24 3232100% (89%-100%)

References

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  • 1
    Martinot-Peignoux M, Stern C, Maylin S, et al. Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. HEPATOLOGY 2010; 51.
  • 2
    Rumi MG, Aghemo A, Prati GM, D'Ambrosio R, Donato MF, Soffredini R, et al. Randomized study of peginterferon-alpha2a plus ribavirin vs peginterferon-alpha2b plus ribavirin in chronic hepatitis C. Gastroenterology 2010; 138: 108-115.
  • 3
    Doglio A, Laffont C, Caroli-Bosc FX, Rochet P, Lefebvre J. Second generation of the automated Cobas Amplicor HCV assay improves sensitivity of hepatitis C virus RNA detection and yields results that are more clinically relevant. J Clin Microbiol 1999; 37: 1567-1569.
  • 4
    Kawai S, Yokosuka O, Kanda T, Imazeki F, Maru Y, Saisho H. Quantification of hepatitis C virus by TaqMan PCR: comparison with HCV Amplicor Monitor assay. J Med Virol 1999; 58: 121-126.

Alessio Aghemo MD*, Maria Grazia Rumi MD*, Stella De Nicola MD*, Massimo Colombo MD*, * A. M. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.