Current guidelines for treating patients with chronic genotype 1 hepatitis C virus (HCV) infection recommend considering discontinuation of therapy after 12 weeks if HCV RNA has not dropped by at least 2 log10 in patients treated with pegylated interferon plus ribavirin. This “stopping rule” is dependent on the sensitivity of the test used to measure early response.

This study evaluated whether minimal residual HCV viremia predicts relapse in patients with early virological response to therapy. The researchers analyzed week 12 HCV viral kinetics and later response in 773 treatment-naive genotype 1 patients receiving pegylated interferon (either Pegasys or Peg-Intron) plus ribavirin at an outpatient clinic.

Results

• Using standard quantitative HCV RNA assays, 75% of treated patients (430 out of 773) showed an early virological response at week 12 (viral load decrease ≥ 2 log10).

• When 222 available serum samples from early virological responders were re-analyzed using a more sensitive real-time PCR test with a lower limit of detection of 10 IU/mL (TaqMan), residual HCV was detected in 84 patients (38%).

• The presence of residual viremia was highly correlated with HCV relapse after the end of 48 weeks of treatment (P < 0.001).

• Residual viremia at week 12 was detectable by the real-time TaqMan PCR test in 15% of sustained responders (19 out of 126), compared with 72% of relapsers (69 out of 96) (P < 0.001).

• Relapse occurred in 78% of patients (68 out of 88) who had detectable residual HCV viremia at week 12, compared with 19% of patients (25 out of 134) who still had undetectable HCV RNA at week 12 using the sensitive test.

Conclusion

The researchers concluded that using a highly sensitive real-time PCR test to detect minimal residual hepatitis C viremia at week 12 of treatment is “a valuable prognostic tool for the prediction of individual treatment outcome.” They suggested that patients who still had detectable HCV viremia at week 12 should have their treatment intensified either by prolonging treatment duration or by using granulocyte-macrophage colony-stimulating factor (GM-CSF) or erythropoietin to prevent dose-reduction of pegylated interferon or ribavirin.

5/30/06

Reference

A Bergk, C. Sarrazin, M von Wagner, and others. Reliable early prediction of viral relapse by detection of minimal residual hepatitis C viremia at treatment week 12. Abstract 176. DDW 2006. May 20-25, 2006. Los Angeles, CA.