4-Week Response to Anti-HCV Treatment Predicts Outcome

A substantial proportion of patients with chronic hepatitis C virus (HCV) infection do not respond to interferon-based therapy. By determining early in the course of treatment which individuals are likely to achieve sustained virological response (SVR), patients may be spared the side effects and expense of unnecessary additional treatment.

Current models used to predict response to treatment with pegylated interferon plus ribavirin are generally based on viral decline during the first 12 weeks of therapy; however, some research indicates that rapid virological response at Week 4 may also be used as a "stopping rule."

As reported in the October 2006 Journal of Viral Hepatitis, French researchers developed a multivariate model to predict SVR or non-response at baseline and during the first 12 weeks of therapy. They based the model on data from 186 patients with chronic hepatitis C treated with pegylated interferon plus ribavirin. The model employed ordinal regression with similarity least squares technology to assign the probability of a given outcome.

Model variables included sex, age, prior treatment status, HCV genotype, baseline serum alanine aminotransferase (ALT) level, histological necro-inflammation and fibrosis scores, and serum HCV RNA levels at baseline and at 4, 8, and 12 weeks.

Results

A multivariate model demonstrated that the model demonstrated high performance values at all time points.

At baseline, the model demonstrated a negative predictive value (NPV) of 91% and a positive predictive value (PPV) of 95%.

At Week 4, these values improved to 97% and 100%, respectively, with 95% sensitivity, 89% specificity, and 93% accuracy.

At Week 4, the model was equally efficient for treatment-naive and previously treated patients.

Internal validation demonstrated 90% PPV, 94% NPV, 95% sensitivity, 88% specificity, and 92% accuracy.

Conclusion

The researchers concluded that, "A Week 4 stopping rule for patients with chronic hepatitis C treated with peginterferon with ribavirin might be proposed by using the model developed in our study."

Inserm U481, Service d'Hepatologie, Hopital Beaujon, Clichy, France.

10/10/06

Reference
M Martinot-Peignoux, L Comanor, J M Minor, and others. Accurate model predicting sustained response at week 4 of therapy with pegylated interferon with ribavirin in patients with chronic hepatitis C. Journal of Viral Hepatitis 13(10): 701-707. October 2006.