IP-10 Correlates with Hepatitis C Viral Load, Hepatic Inflammation and Fibrosis and Predicts Hepatitis C Virus Relapse or Non-Response in HIV–HCV Coinfection

Abstract

BackgroundInterferon (IFN)-γ inducible protein 10 (IP-10) is increased in hepatitis C virus (HCV) monoinfection, correlates with hepatic inflammation and predicts non-response (NR) to antiviral therapy. We aimed to clarify the role of IP-10 in HIV-HCV coinfection.MethodsSerum IP-10 levels of 30 HIV-HCV- coinfected patients treated with pegylated (PEG)-IFN-α2a (180 μg/week) and ribavirin (800-1,200 mg/day) were measured at baseline and 24 h after first IFN dose. The predictive value of IP-10 was compared with established markers of treatment outcome by applying a multivariate logistic regression model.ResultsPatients with NR (476 ±156 pg/ml) or virological relapse (508 ±298 pg/ml) had significantly higher baseline IP-10 levels compared with patients who had a sustained virological response (SVR; 293 ±97 pg/ml, P=0.001). The IFN-induced increase of IP-10 was significantly stronger in patients with an SVR ( P=0.017). IP-10 levels were associated with HCV viral load, alanine aminotransferase (ALT) levels, hepatic inflammatory activity and fibrosis stage. Advanced fibrosis, high HCV viral load, hepatovenous pressure gradient and pretreatment IP-10>400 pg/ml predicted NR to antiviral therapy. In the multivariate analysis, IP-10 was identified as the strongest baseline predictor of SVR with a specificity and sensitivity of 83.4% and 92.9%, respectively.ConclusionsPretreatment IP-10 levels correlated with HCV viral load, ALT levels, hepatic inflammation and fibrosis. An IP-10 cutoff level of 400 pg/ml might serve as a useful predictive marker for anti-HCV therapy in HIV–HCV-coinfected patients because it could discriminate patients with expected NR or HCV relapse after therapy from patients with an SVR before starting antiviral treatment.