Detectable HCV RNA at Week 8 Is Best Predictor of Relapse in Genotype 1
Current standard therapy for chronic hepatitis C virus (HCV) infection -- pegylated interferon plus ribavirin for 48 weeks -- produces a sustained virological response (SVR) in about half of treated patients, prompting researchers to explore alternative treatment strategies and look for predictors of good outcomes.
Peter Ferenci from the University of Vienna in Austria and colleagues recently demonstrated in a large randomized controlled trial that extending the duration of treatment with pegylated interferon alfa-2a (Pegasys) plus ribavirin reduced the risk of relapse and increased the SVR rate in patients with hard-to-treat HCV genotypes 1 or 4 who did not achieve rapid virological response (RVR), or undetectable HCV RNA at week 4 of treatment.
In an analysis presented at the recent Digestive Disease Week annual meeting (DDW 2009) in Chicago, Ferenci and colleagues sought to determine which of these non-RVR patients would benefit most from extended treatment, looking at associations between SVR and relapse rates and HIV RNA levels at weeks 8 and 12.
The present analysis included 187 chronic hepatitis C patients enrolled at one center (34% of all recruited participants in the larger study). Participants who still had detectable HCV RNA at week 4, but who experienced more than a 2 log decrease or had HCV RNA < 50 IU/mL at week 12 (early virologic response, or EVR), were randomly assigned to receive treatment for either 48 or 72 weeks.
A total of 97 patients achieved EVR, of whom 52 were assigned to received the 48-week regimen (all competed treatment) and 45 received the 72-week regimen (41 completed treatment). Blood samples obtained at weeks 2, 4, 8, and 12 were retested using a sensitive viral load test with a limit of detection of 10 IU/mL.
Patients with undetectable HCV RNA at weeks 8 and 12 had high SVR rates with either 48 or 72 weeks of treatment:
Undetectable HCV RNA at week 8: 91% with 48-week regimen, 100% with 72-week regimen;
Undetectable HCV RNA at week 12: 81% and 82%, respectively;
If HCV RNA remained detectable at weeks 8 and 12, SVR rates were low:
Detectable HCV RNA at week 8: 37% with 48-week regimen, 54% with 72-week regimen;
Detectable HCV RNA at week 12: 29% and 33%, respectively.
Regardless of treatment duration, only 2 of 35 participants (6%) with undetectable HCV RNA at week 8 experienced relapse, for a negative predictive value (NPV) of 94%.
Of the 25 patients who achieved undetectable HCV RNA between 8 and 12 weeks, 7 (28%) relapsed, yielding an overall NPV of 72% (60% for the 48-week regimen, 80% for the 72-week regimen).
Participants who had detectable HCV RNA at both 8 and 12 weeks had a lower relapse rate and a higher SVR rate with the longer treatment duration.
Based on these findings, the investigators concluded, "Measurement of HCV RNA at week 8 is the optimal time to identify patients most likely to benefit from extended [pegylated interferon alfa-2a] plus ribavirin combination therapy."
Internal Medicine 3, Medical University of Vienna, Vienna, Austria; Department of Clinical Virology, Medical University of Vienna, Vienna, Austria.
P Ferenci, TM Scherzer, H Kerschner, and others. Week 8 HCV-RNA Is the Optimal Predictor of Relapse in non-RVR Patients with Genotype 1/4 Randomized to 48 or 72 Weeks PEG-IFN Alfa-2a Plus RBV. Digestive Disease Week (DDW 2009). Chicago. May 30-June 4, 2009. Abstract M1811.