Value of von Willebrand factor antigen as a predictor of response to antiviral therapy in patients suffering from chronic hepatitis C

Background: Von Willebrand factor Antigen (vWF-Ag) is an acute phase protein which increases during combination antiviral therapy. As yet there is no validated method of differentiating between sustained virological responders and relapsers during the therapy of hepatitis C. We therefore investigated whether levels of vWF-Ag during combination antiviral therapy can predict sustained virological response (SVR), and whether vWF-Ag already allows a differentiation between patients who will relapse and those who will experience a SVR during therapy.

Methods: 108 consecutive patients with chronic hepatitis C were included. Patients with genotype 1 or 4 (n=77) received 180µg PEG-IFN-! 2a 1/week and 1000–1200mg ribavirin daily over a period of 48 weeks. Patients with genotype 2 or 3 (n=31) received 180µg PEGIFN-! 2a 1/week and 800mg ribavirin daily over a period of 24 weeks. vWF-Ag levels were measured before, during, and 6 months after combination therapy. Results are given as means±95% confidence intervals (CI).

Results: 81 patients experienced a sustained virological response (SVR), while relapse (R) occured in 27 patients. Baseline vWF-Ag level was a mean 183% (168–197%) and did not differ significantly between the group of patients with SVR and the group that relapsed.

vWF-Ag peaked at 267% at week 4 (95%CI: 249–286%) in the SVR group, while a maximum mean value of 315% was reached in the R group at week 16 (95%CI: 270–359%).

The vWF-Ag level was higher in relapsers than in SVR starting at week 8 of therapy and the difference in levels was most significant at week 24 of therapy: mean 307% (95% CI:272–344%) vs. 244% (95% CI: 226–262%), p<0,01). Accordingly, 6 months after the end of therapy vWF-Ag was higher in relapsers than in SVR (165%; CI: 129–201% vs. 126%; CI: 114–137%;p<0,05). ROC-curve analysis at week 4 revealed that the specificity for prediction of a relapse is 82%, when vWF-Ag levels are >313%. Also, at week 4 the negative predictive value of vWF-Ag levels <313% is 86.1%.

Conclusion: The increase in vWF during combination antiviral therapy is significantly higher in patients who will relapse than in patients who will experience a SVR. The difference between the two groups is significant as early as week 8 of therapy. This can be explained by systemic inflammation induced by hepatitis C virus. Further studies in larger patients groups are needed to investigate a possible predictive value of vWF on SVR.

Literature: Jilma 1999, Am J Respir Crit Care Med Homoncik 2005, AP&T