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Reliable early prediction of viral relapse by detection of minimal residual hepatitis C viremia at treatment week 12 with Sensitive HCV Viral load Test
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DDW, Los Angeles, May 21-24, 2006 (Digestive Disease Week)
A. Bergk1; C. Sarrazin2; M. von Wagner2; G. Teuber3; P. Buggisch4; V. Weich1; B. Wiedenmann1; T. Berg1
1. Hepatology and Gastroenterology, Charite, CVK, Berlin, Germany.
2. Internal Medicine II, Universitaetsklinikum des Saarlandes, Homburg, Germany.
3. Internal Medicine II, UniversitaetsklinikumFrankfurt, Frankfurt am Main, Germany.
4. Center for Internal Medicine, Universitaetsklinikum Hamburg, Hamburg, Germany.
Current treatment guidelines for the therapeutic management of chronic hepatitis C virus (HCV) genotype 1 infected patients include a week 12 stopping rule for nonresponders defined by a drop of viral load less than 2 log10 in patients treated with pegylated interferon and ribavirin. Nevertheless there has been no convincing prognostic tool to easily and reliably predict viral relapse after the end of 48 weeks of treatment.
The aim of the present study was to evaluate the predictive value of a minimal residual HCV viremia for a relapse in genotype 1 infected patients with early virologic response to therapy.
Investigators retrospectively analyzed viral kinetics at week 12 and response of 773 treatment naive HCV genotype 1-infected patients using PegIFNa-2a/b and ribavirin treated at our outpatient clinics. For the detection of residual viremia at week 12 a quantitative real-time PCR with a lower limit of detection of 10IU/mL (TaqMan) was used.
Results:
Using standard quantitative HCV-RNA assays at week 12 75% (430/773) of the patients treated with PegIFNa-2a/b and ribavirin showed an early virologic response defined by week 12 viral load drop ≥2 log10. By re-analyzing 222 available serum samples of early virologic responders by TaqMan a residual viremia could be detected in 84 out of 222 patients (38%). The presence of viremia highly correlated with a viral relapse after the end of 48 weeks of treatment (p<0,001). Residual viremia was detectable by real-time PCR at week 12 in only 19 out of 126 sustained responders (15%) as compared to 69 out of the 96 relapse patients (72%) (p<0,001).
A relapse occurred in 78% of the patients who had detectable HCV viremia at week 12 (68/88) as compared to only 19% (25 out of 134 patients) if HCV RNA was undetectable at week 12. The relative risk to suffer from a relapse was 3.5 and 0.26 in patients with and without residual hepatitis C viremia at week 12, respectively (p<0,001).
Discussion: Using a highly sensitive real-time PCR the detection of minimal residual hepatitis C viremia at treatment week 12 was in 78% associated with a viral relapse after the end of therapy and is therefore a valuable prognostic tool for the prediction of individual treatment outcome. Treatment of patients with detectable viremia at week 12 should be individually intensified by either prolonging treatment duration or preventing dose reductions by the application of erythropoetin or GM-CSF.
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