title: Impact of hepatic immunoreactivity of angiotensin-converting enzyme 2 on liver fibrosis due to non-alcoholic steatohepatitis.
abstract: BACKGROUND
  We aimed to evaluate the hepatic immunoreactivity of angiotensin-converting enzyme 2 (ACE2) in non-alcoholic steatohepatitis (NASH) patients, elucidate its association with the clinicopathological characteristics and also determine its role in fibrosis progression.
  
  
  METHODS
  The consecutive biopsy proven NASH patients were subdivided into two groups according to their fibrosis score. Fibrotic stages<3 in mild fibrosis group and fibrotic stages ≥ 3 in advanced fibrosis depending on the presence of bridging fibrosis. Liver biopsy specimens were immunohistochemically stained for ACE2 immunoreactivity. Demographics and clinical properties were compared between the groups. Univariate and multivariate analysis were also performed to evaluate the independent predicting factors for the presence of advanced liver fibrosis caused by NASH.
  
  
  RESULTS
  One hundred and eight patients were enrolled in the study. Out of this, ninety-four patients representing 87% were classified as mild fibrosis group, whilst fourteen representing 13% were in advanced fibrosis group. We compared high hepatic immunoreactivity of ACE2 between mild and advanced fibrosis groups and found a statistically significant difference 65.9% vs 28.5%, respectively and P=0.008. Hepatic ACE2 immunoreactivity was inversely correlated with the fibrosis score (r: -0.337; P<0.001). The significant variables in the univariate analysis were then evaluated in multivariate logistic regression analysis and hepatic ACE2 immunoreactivity was an independent predicting factor of liver fibrosis [odds ratio (OR): 0.194; 95% confidence interval (CI): 0.082-0.897, P=0.036].
  
  
  CONCLUSIONS
  Hepatic immunoreactivity of ACE2 was inversely correlated with the liver fibrosis among biopsy proven NASH patients and it was also an independent predicting factor of advanced fibrosis.
authors.affiliation: Dr. A.Y. Ankara Oncology Training and Research Hospital, Department of Gastroenterology, 06200 Ankara, Turkey. Electronic address: drmustafacen@gmail.com.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Cengiz
authors.affiliation: Gazi University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey.
authors.forename: Seren
authors.initials: S
authors.lastname: Ozenirler
authors.affiliation: Gazi University Faculty of Medicine, Department of Pathology, Ankara, Turkey.
authors.forename: Guldal
authors.initials: G
authors.lastname: Yılmaz
authors.affiliation: Ufuk University Faculty of Medicine, Department of Gastroenterology, Ankara, Turkey.
authors.forename: Gulbanu
authors.initials: G
authors.lastname: Erkan
mesh_terms: D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D007703:Peptidyl-Dipeptidase A / Q000276:immunology*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2