IP-10 Levels Predict Treatment Response in Patients with Hepatitis C

By Liz Highleyman

It is evident that some people are more likely to clear hepatitis C virus (HCV) with antiviral therapy, but the biological mechanisms underlying treatment response are not well understood.

Interferon-gamma-inducible protein-10 (IP-10) is a cytokine (chemical messenger) produced by monocytes, lymphocytes, and other cells. Its production is stimulated by interferon-gamma (IFN-gamma), and past studies suggest it plays a role in cell proliferation, angiogenesis (blood vessel generation), and apoptosis (programmed cell death).

Researchers at the University of Goteborg in Sweden investigated associations between IP-10 levels and liver histology, HCV viral kinetic response, and treatment outcome in individuals with chronic hepatitis C.

The study included 265 HCV positive patients. Plasma IP-10 was measured before, during, and after treatment with pegylated interferon alpha-2a (Pegasys) plus ribavirin.

Results

By univariate analyses, a low baseline IP-10 level was significantly associated with:

- Normal body weight (body mass index < 25 kg/m2);
- Low baseline HCV viral load;
- Rapid virological response (RVR) to treatment;
- Sustained viral response (SVR);
- Less pronounced liver fibrosis;
- Less liver inflammation;
- Less steatosis, among patients with HCV genotypes other than 3.

By multivariate analysis, low plasma IP-10, low baseline HCV viral load, and genotype 2 or 3 HCV were independent predictors of RVR and SVR.

IP-10 levels decreased 6 weeks into treatment and remained low in patients who eventually achieved SVR.

In contrast, plasma IP-10 levels rebounded in patients who continued to have detectable HCV RNA after completion of treatment.

Using cutoff IP-10 levels of 150 and 600 pg/mL for predicting SVR in patients with genotype 1 HCV had a specificity of 81% and a sensitivity of 95%.

Conclusion

In conclusion, the authors wrote, "Baseline IP-10 levels are predictive of the response to HCV treatment."

It remains to be determined whether interventions that raise IP-10 levels could improve the likelihood of treatment response.

09/22/06

Reference
A I Romero, M Lagging, J Westin, and others. Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN- alpha 2a and ribavirin for chronic hepatitis C virus infection. Journal of Infectious Diseases 194(7): 895-903. October 2006.