title: Serum PAI-1 is a novel predictor for response to pegylated interferon-α-2b plus ribavirin therapy in chronic hepatitis C virus infection.
abstract: Obesity and insulin resistance have been reported as negative predictors for sustained virological response (SVR) in hepatitis C virus (HCV) genotype 1 infected patients treated with pegylated interferon-α plus ribavirin. They are also known to affect serum levels of several cytokines including adipocytokines. But the association between these cytokines and treatment outcome has not been fully elucidated. We examined pretreatment serum levels of 14 cytokines among 190 patients who were treated with pegylated interferon-α-2b plus ribavirin for chronic HCV-1b infection with high viral load (≥ 5 log IU/mL) and analyzed their contribution to treatment response. Plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor, and 11 clinical factors showed significant association with SVR in univariate logistic regression analysis. Four significant factors in multivariate analysis; serum PAI-1 (odds ratio [OR] = 15.42), body mass index (OR = 4.56), rs8099917 (OR = 4.95) and fibrosis stage (OR = 5.18) were identified as independent predictors. We constructed a simple and minimally invasive prediction score for SVR based on the presence of these factors except for fibrosis stage. The accuracy of this score was 73%, and was confirmed using an independent validation cohort consisting of 31 patients (68%). The strongest correlation was between PAI-1 level and platelet count (r = 0.38, P = 1.8 × 10(-7)), and PAI-1 level was inversely correlated with fibrosis stage. Serum PAI-1 is a novel predictor for the response to combination therapy against chronic HCV-1b infection and may be associated with liver fibrosis.
authors.affiliation: Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Hiroshima, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Miki
authors.forename: W
authors.initials: W
authors.lastname: Ohishi
authors.forename: H
authors.initials: H
authors.lastname: Ochi
authors.forename: C N
authors.initials: CN
authors.lastname: Hayes
authors.forename: H
authors.initials: H
authors.lastname: Abe
authors.forename: M
authors.initials: M
authors.lastname: Tsuge
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Chayama
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood*; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011379:Prognosis; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D044967:Serum / Q000737:chemistry; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; C051321:SERPINE1 protein, human; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b