Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection

Abstract

Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic HCV. In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 300 individuals, 245 (181 male, 47 HIV+) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV co-infection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n=137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248±32 vs. 142±22 pg/mL, P=0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P=0.048) and 16% (27 of 165) and in those in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favourable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance. Conclusion High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance.

Predictive Value of Serum IFN-γ inducible Protein-10 and IFN-γ/IL-4 Ratio for Liver Fibrosis Progression in CHB Patients

“…Multiple studies have shown that IP-10 plays an important role in the development and progression of liver disease, in which IP-10 binds to chemokine CXCR3 and recruits activated T lymphocytes to the liver parenchyma262728. To date, investigations of IP-10 and its correlations with viral clearance and liver fibrosis have been mainly focused on HCV-infected patients161718192021. High IP-10 levels at acute HCV detection are associated with failure to clear HCV spontaneously, and patients with low levels of IP-10 should defer therapy for potential spontaneous clearance18.…”

“…To date, investigations of IP-10 and its correlations with viral clearance and liver fibrosis have been mainly focused on HCV-infected patients161718192021. High IP-10 levels at acute HCV detection are associated with failure to clear HCV spontaneously, and patients with low levels of IP-10 should defer therapy for potential spontaneous clearance18. The IP-10 levels are higher in patients with chronic HCV infection than in healthy controls, and they are positively associated with the severity of liver fibrosis in CHC patients.…”

“…It has been reported that serum and intrahepatic IP-10 levels are increased in HCV-replicating cells and patients with HCV infection151617. Furthermore, associations between serum IP-10 and HCV spontaneous clearance have shown the value of serum IP-10 for the early diagnosis of hepatic fibrosis and treatment outcomes with IFN-based therapy in patients with chronic hepatitis C (CHC)161718192021. Interestingly, the N-terminal truncated, short form of IP-10 (3–77aa), resulting from the post-translational modification by dipeptidyl peptidase-4 (DPP4), did not show any correlation with the outcome in HCV patients treated with Sofosbuvir/Ribavirin, an IFN-free therapy22.…”

Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells

“…Nitric oxide (NO), a paracrine-acting soluble gas, possesses a wide-range biology effects and is synthesized by NO synthase [7] from L-arginine. Three isoforms of nitric oxide synthase (NOS) have been identified as neuronal NOS (nNOS/NOS1), inducible NOS (iNOS/NOS2), and endothelial NOS (eNOS/NOS3).…”

Coinfection with Hepatitis C Virus among HIV-1-Infected Individuals Increases Proinflammatory Cytokines and HIV-1 Disease Severity

“…During HCV infection, hepatocytes produce IP-10 and circulating levels of IP-10 are known to be measurable during chronic HCV infection [37]. High levels of IP-10 levels are known to be associated with reduced rates of sustained virological response during treatment of HCV with pegylated (PEG)-IFN/ribavirin (RBV) [37,[47][48][49] HIV-1/HCV coinfection [38,50] and reduced spontaneous clearance to acute infection [51]. Further, high IP-10 levels have been associated with greater inflammation and liver fibrosis [48,49] even in a cohort of African-American injection drug users with chronic HCV [52].…”