IP-10 predicts HCV clearance, relapse or nonresponse in HIV-HCV-coinfection

Introduction: Interferon gamma inducible protein 10 (IP-10) is elevated in hepatitis C virus (HCV) mono-infection, correlates with hepatic inflammation and predicts nonresponse (NR) to antiviral therapy. We aimed to clarify the pathogenetic role and the predictive value of IP-10 in HCV-HIV-coinfection.

Methods: IP-10 levels of 30 HIV-HCV-coinfected patients undergoing 48 weeks of antiviral therapy with pegylated-interferon-! 2a (180“g/week) and ribavirin (800–1200mg/day) were measured at baseline and 24 hours after first IFN dose.

Associations between IP-10 and histological findings, hepato-venous pressure gradient (HVPG), liver enzymes and HIV and HCV viral load were analysed. By applying a multivariate logistic regression model we determined the predictive value of IP-10 compared to other factors for a sustained virological response (SVR).

Results: IP-10 levels in patients with virological relapse (688±283pg/ml) nonresponse (NR) or virological relapse after therapy had significantly higher baseline (mean: 688±283 pg/mL) compared to patients with SVR (286±94 pg/mL; p=0.001).

The IFN induced increase of IP-10 was significantly stronger in patients with SVR (p=0.017). Higher IP-10 levels were associated with higher HCV and HIV viral load, higher necro-inflammatory activity and advanced fibrosis. By univariate analysis advanced fibrosis, high HCV viral load, elevated HVPG and pre-treatment IP-10 >400pg/mL were markers of treatment response. In the multivariate model IP-10 was identified as the strongest baseline parameter predicting SVR with a specifity and sensivity of 83.4% and 92.9%, respectively.

Discussion: Pretreatment IP-10 levels may serve as useful markers predicting response to anti-HCV therapy in HIV-HCV-coinfected patients, since we showed that it is possible to discriminate patients with expected NR or HCV-relapse after therapy from patients with an SVR using an IP-10 cut-off at 400 pg/mL.