Session Title: Category 5g. VIRAL HEPATITIS: g. HEPATITIS C - CLINICAL (THERAPY)
Presentation Date: Apr 15, 2010
RELATIONSHIP OF SERUM IP-10 LEVELS WHICH REFLECTS HEPATIC INTERFERON STIMULATING GENE INDUCTION AND ANTIVIRAL EFFECT OF PEG/RBV COMBINATION THERAPY IN PATIENT WITH CHRONIC HEPATITIS C
Y. Karino*, J. Toyota, T. Arakawa, Y. Kuwata, J. Akaike, I. Ozeki, T. Sato, T. Ohmura
Hepatology Unit, Sapporo Kosei General Hospital, Sapporo, Japan. *firstname.lastname@example.org
Background and aims: Relations between induction of interferon stimulated gene (ISG) and antiviral effect of PEG-IFN and ribavirin therapy (PEG/RBV) are reported. HCV is recognized by a natural immunity and activates endogenous IFN production. IP-10 is IFN induced protein produced in a liver in HCV infection. We reviewed the relation between serum IP-10 level, an index of hepatic ISG expression, and antiviral effect of PEG/RBV.
Methods: 142 patients with genotype 1b were included in analysis. We examined as a host factor, age, gender, liver histology, blood biochemistry and serum IP-10, as a virus factor, HCV RNA (Taqman HCV) and amino acid mutation of core 70 and ISDR, and as a treatment factor serum level of RBV.
Results: IP-10 (initial value) showed significant correlation with age (r=0.206, P=0.015), hepatic inflammation (r=0.388, P< 0.0001), hepatic steatosis (r=0.209, P=0.019), ALT (r=0.327, P=0.0001), gamma-GTP (r=0.297, P=0.001) and HCV RNA (r=0.288, P=0.001). IP-10 level was significantly low in aa70 wild cases (p< 0.001). During PEG/RBV IP-10 level changed 465pg/ml (initial), 7147pg/ml (8 hours), 2339pg/ml (24 hours) and half life was 2.69 days. IP-10 response (24 hours/initial) showed significant correlation with hepatic fibrosis (r=-0.255, P=0.006), hepatic steatosis (r=-0.203, P=0.028), ALT (r=0.311, P=0.0003), gamma-GTP (r=-0.256, P=0.004) and delta HCV RNA (initial -24hours) (r=0.433, P< 0.001). IP-10 response was high in aa70 wild cases (6.6 vs 4.4, P< 0.001). Mean initial IP-10 level in each antiviral effect of PEG/RBV was SVR: 385pg/ml, ETR: 365pg/ml, and NVR: 541pg/ml. NVR showed significantly high IP-10 level (P=0.0005). NVR was distinguished by the following; distinction formula =-3.250 + 0.002 x P-10 + 0.574 x HCV RNA - 0.910 x aa70 mutation (non-Wild=1, Wild=2). IP-10 was revealed to be a NVR predicting factor. When limit it to HCV RNA> 6log IU/ml, regulatory factor of initial IP-10 was gender, hepatic fibrosis, total clearance of RBV (CL/F), ALT and gamma-GTP, and that of IP-10 response was aa70 mutation, CL/F, initial IP-10 and HCV RNA by multi-regression analysis.
Conclusions: High ISG induction by endogenous IFN tended to lead NVR and influence of aa70 mutation was suggested in the degree of induction of ISG by exogenous IFN.