title: TIMP-1 in patients with cirrhosis: relation to liver dysfunction, portal hypertension, and hemodynamic changes.
abstract: OBJECTIVE
  Cirrhotic portal hypertensive patients often develop hemodynamic complications and the diagnosis is often based on liver biopsy and measurements of the hepatic venous pressure gradient (HVPG). Potential noninvasive biomarkers for the severity of cirrhosis are the matrix metalloproteinase and their specific inhibitors such as tissue inhibitor of metalloproteinases-1 (TIMP-1). The aim of the study was to investigate TIMP-1 levels in cirrhosis in relation to the degree of liver dysfunction, portal hypertension, and hemodynamic changes.
  
  
  METHODS
  We retrospectively studied 84 patients with cirrhosis and 14 controls without liver disease. All individuals underwent a liver vein catheterization with a hemodynamic assessment. TIMP-1 was determined in arterial and hepatic venous plasma using an MAC-15 TIMP-1 ELISA.
  
  
  RESULTS
  Hepatic venous concentrations of TIMP-1 were significantly increased in patients compared to controls: 336 (166) ng/ml versus 145 (100) (median/IQ range) (p < 0.001) with a progressive increase throughout the Child classes (p < 0.001). Circulating TIMP-1 correlated significantly with indocyanine green clearance (r = -0.44, p < 0.0001), Child Turcotte score (r = 0.50, p < 0.0001), HVPG (r = 0.40, p < 0.0001), mean arterial pressure (r = -0.29, p = 0.008), and systemic vascular resistance (r = -0.23, p = 0.03). Receiver operating characteristic curve analysis enabled us to establish cutoff values for TIMP-1 with regard to portal hypertension.
  
  
  CONCLUSIONS
  TIMP-1 is significantly increased in patients with cirrhosis and correlates with the severity of the disease, degree of portal hypertension, and vasodilatory state. TIMP-1 is therefore a promising new noninvasive marker to predict hemodynamic-related complications in cirrhosis.
authors.affiliation: Department of Clinical Physiology and Nuclear Medicine, Centre of Functional Imaging and Research, Copenhagen University Hospital Hvidovre , Copenhagen , Denmark.
authors.forename: Troels M
authors.initials: TM
authors.lastname: Busk
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Vibeke
authors.initials: V
authors.lastname: Jensen
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
mesh_terms: D000328:Adult; D000368:Aged; D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D005260:Female; D006499:Hepatic Artery; D006503:Hepatic Veins; D006801:Humans; D006975:Hypertension, Portal / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012189:Retrospective Studies; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D014655:Vascular Resistance
chemical_list: D015415:Biomarkers; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1
keywords: TIMP-1; biomarker; cirrhosis; portal hypertension