title: Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance.
abstract: The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy. GEE analysis showed that PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes affected PAI-1 levels early and late in therapy, respectively. At 24 weeks post-therapy, higher lipid, brain natriuretic peptide, homocysteine and PAI-1 levels and PAI-1 activity were noted only in SVR patients compared with pre-therapy levels. Within 24 weeks post-therapy, 2.2% of the SVR (mean age: 57.8 yr; 8 smoking males; the 2 females had pre-therapy hypercholesteremia or cardiovascular family history of disease) and 0% of the non-SVR patients experienced a new cardiovascular event. Platelet counts consistently correlated with PAI-1 levels regardless of HCV infection. PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes mainly affected PAI-1 levels longitudinally. Within 24 weeks post-anti-HCV therapy, the SVR patients showed increasing PAI-1 levels with accelerating cardiovascular risk, especially the vulnerable cases.
authors.affiliation: Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Chang
authors.affiliation: Department of Cardiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Healthcare center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Graduate Institute of Health-Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.|Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Li-Heng
authors.initials: LH
authors.lastname: Pao
authors.affiliation: Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Cheng-Tang
authors.initials: CT
authors.lastname: Chiu
mesh_terms: D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D008954:Models, Biological; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics*; D010976:Platelet Count; D012367:RNA, Viral; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; D012367:RNA, Viral; C051321:SERPINE1 protein, human