Clinical

Interferon protein predicts hepatitis C response

Last Updated: 2006-03-03 15:53:45 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Pretreatment levels of interferon gamma inducible protein 10 (IP-10) are associated with sustained virological response of hepatitis C to treatment with peginterferon and ribavirin, according to a report in the March issue of Gut.

"Genotype 1-infected patients with low serum IP-10 levels before therapy have a higher probability of response to antiviral therapy than those with elevated IP-10 concentrations," Dr. Carmelo Garcia-Monzon from University Hospital Santa Cristina, Madrid, told Reuters Health.

Dr. Garcia-Monzon and colleagues evaluated the relationship between pretreatment serum IP-10 levels and the virological response to peginterferon plus ribavirin therapy in 137 patients chronically infected with hepatitis C virus.

Seventy-nine of the patients (57.7%) achieved a sustained virological response, the authors report, and 58 patients (42.3%) were nonresponders.

In a multivariate logistic regression analysis of all patients, only non-1 genotype and low baseline viral load were independent predictors of a sustained virological response.

When only patients infected with genotype 1 were considered, pretreatment IP-10 levels and baseline viral load were independent predictors of a sustained virological response.

Among all hepatitis C virus-infected patients, those with a sustained virological response had significantly lower pretreatment serum IP-10 levels than the nonresponders, the report indicates, but there was no significant difference in serum IP-10 levels between the groups after 12 weeks of treatment.

Pretreatment IP-10 levels were significantly higher in patients with genotype 1 or with advanced fibrosis, the researchers note, but there was no association between pretreatment IP-10 levels and sex, viral load, or grade of necroinflammatory activity from the pretreatment liver biopsy.

"Based on our results, IP-10 may have a role in failure of antiviral therapy in patients with chronic HCV infection," the investigators suggest. "However, the mechanism by which IP-10 modulates the efficacy of peginterferon plus ribavirin therapy remains elusive, but it is conceivable that it is related to its biological functions."

"Our clinical results suggest that IP-10 might interfere with antiviral activity of interferon alpha in the liver," Dr. Garcia-Monzon said. "We are planning to carry out studies on cultured hepatocytes in order to determine whether IP-10 modulates interferon-mediated antiviral response. Understanding the molecular basis of IP-10 effects on target cells could provide strategies for improving the antiviral therapy in chronic HCV infection."

"Predicting response to antiviral therapy is a crucial point in the management of patients with chronic HCV infection," Dr. Garcia-Monzon concluded. "We have shown that IP-10 could be important for optimizing therapy in genotype 1 patients who are the most difficult to cure. Definitive conclusions on this issue, however, must await validation studies worldwide."

Gut 2006;55:374-379.