title: Elevated levels of endothelin-1 in hepatic venous blood are associated with intrapulmonary vasodilatation in humans.
abstract: BACKGROUND
  Hepatopulmonary syndrome is a pulmonary vascular complication of cirrhosis in which intrapulmonary vasodilatation (IPV) results in hypoxemia. Endothelin-1 (ET-1), produced by proliferating cholangiocytes, has been identified as a mediator of IPV in an animal model of HPS, but the pathophysiology of IPV in humans has not been defined.
  
  
  OBJECTIVE
  The purpose of this study was to assess whether cirrhosis with IPV, which often leads to HPS, is associated with increased hepatic venous ET-1 blood levels.
  
  
  METHODS
  We performed a prospective cohort pilot study of 40 patients with liver disease undergoing transjugular liver biopsy from November 1, 2008 to September 1, 2009. Patients were categorized according to absence (-) or presence (+) of IPV as determined by bubble-contrasted echocardiography. Hepatic venous blood was assayed for ET-1 by ELISA. The percent volume of cholangiocytes in the liver biopsy specimen was determined by morphometric analysis, as a measure of bile duct proliferation.
  
  
  RESULTS
  Nine subjects were excluded, due to absence of cirrhosis (6) and patent foramen ovale (3). Of the remaining 31 subjects, IPV was present in 18 (58%). Median hepatic venous ET-1 was higher with IPV+ than IPV- at levels of 9.1 pg/mL (range 7.5-11.7) versus 2.1 pg/mL (1.3-5.6), respectively (P = 0.004). ET-1 levels correlated positively with cholangiocyte percent volume (r = 0.72, P < 0.001) but not with measures of liver dysfunction (bilirubin, INR, MELD score, or hepatic venous pressure gradient).
  
  
  CONCLUSIONS
  In human cirrhosis, increased hepatic venous ET-1 is associated with IPV and increased hepatic cholangiocyte volume.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of South Carolina, ART 7100A, 25 Courtenay Dr. MSC 290, Charleston, SC 29425, USA. kochd@musc.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Koch
authors.forename: Galina
authors.initials: G
authors.lastname: Bogatkevich
authors.forename: Venkat
authors.initials: V
authors.lastname: Ramshesh
authors.forename: John J
authors.initials: JJ
authors.lastname: Lemasters
authors.forename: Renan
authors.initials: R
authors.lastname: Uflacker
authors.forename: Adrian
authors.initials: A
authors.lastname: Reuben
mesh_terms: D001652:Bile Ducts / Q000166:cytology; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D004108:Dilatation, Pathologic; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006503:Hepatic Veins / Q000378:metabolism*; D020065:Hepatopulmonary Syndrome / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011667:Pulmonary Veins / Q000473:pathology*; D014664:Vasodilation
chemical_list: D019332:Endothelin-1