400,000 IU/mL Is the Optimal Baseline Viral Load Cut-off to Predict Response In Treatment-naive Patients with Genotype 1 HCV

Baseline HCV RNA (viral load) is an important predictor of treatment outcome in patients with chronic hepatitis C. The most widely accepted HCV RNA level used to define “high” and “low” pretreatment viral load in studies using conventional (non-pegylated) interferon-based therapy has been 800,000 IU/mL.

Recently, however, 400,000 IU/mL has been proposed as the optimal cut-off to best discriminate high and low viral load, based on the probability of achieving sustained virological response (SVR) in patients treated with pegylated interferon alfa-2a (Pegasys) plus ribavirin.*


The objective of the present French study, presented at the recent 42nd Annual Meeting of the European Association for the Study of the Liver in Barcelona, Spain, was to analyze the predictive value of this viral load cut-off in patients treated with pegylated interferon alfa-2b (PegIntron) plus ribavirin.


The study included 312 patients (177 treatment-naive and 135 with prior treatment experience) consecutively treated with PegIntron plus ribavirin. Patients with genotypes 1, 4, or 5 and prior non-responders received 48 weeks of therapy, while naive patients infected with genotypes 2 or 3 were treated for 24 weeks. Serum HCV RNA was measured using the Versant HCV RNA 3.0 (bDNA) assay (Bayer diagnostics).

Results
 

The overall SVR rate for treatment-naive patients was 54%: genotype 1: 43%; genotype 4: 48%. SVR rates in treatment-naive patients with baseline HCV RNA above and below different cut-off points were as follows: ≤ 400,000 > 400 000: all patients: 73% vs 43%; genotype 1: 63% vs 37%; genotype 2/3: 86%vs 63%; ≤ 600,000 vs > 600,000: all patients: 64% vs 44%; genotype 1: 55% vs 36%; genotype 2/3: 79% vs 66%; ≤ 800,000 > 800,000: all patients: 60% vs 45%; genotype 1: 51% vs 38%; genotype 2/3: 77% vs 66%. The overall SVR rate for treatment-experienced patients was 38%: genotype 1: 31%; genotype 2/3: 72%. SVR rates in treatment-experienced patients with baseline HCV RNA above and below different cut-off points were as follows: ≤ 400,000 vs> 400 000: 40% vs 37%; ≤ 600,000 vs > 600,000: 41% vs 36%; ≤ 800,000 vs > 800,000: 43% vs 35%.

Conclusion

In conclusion, the authors wrote, “Similarly to pegylated interferon alfa-2a plus RBV therapy, the optimal pretreatment viral load cut-off (assessed with Versant HCV RNA 3.0 (bDNA)) for the best prediction of treatment outcome is 400,000 IU/ml, in naive patients (mainly genotype 1) treated with pegylated interferon alpha-2b + ribavirin.”

However, they added, “This cut-off is not efficient for non-naive patients.”

INSERM, U773, Centre De Recherche Biomédicale Bichat-Beaujon CRB3, Hopital Beaujon, Clichy, France; Service D’Hépatologie, Hôpital Beaujon, Clichy, France.



M Martinot-Peignoux, M P Ripault, S Maylin, and others. Optimal Pretreatment Viral Load Cut-off to Predict Treatment Outcome in Patients with Chronic Hepatitis C Treated with Peginterferon Alfa-2b plus Ribavirin. 42nd Annual Meeting of the European Association for the Study of the Liver. Barcelona, Spain. April 11-15, 2007.

*S Zeuzem, M W Fried, K Reddy, and others. Improving the clinical relevance of pre-treatment viral load as a predictor of sustained virological response (SVR) in patients infected with hepatitis C genotype 1 treated with peginterferon alfa-2a (40KD) (Pegasys) plus ribavirin (Copegus). 57th AASLD. October 27-31, 2006. Boston, MA. Abstract 209.