title: Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study.
abstract: OBJECTIVE
  Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH.
  
  
  METHODS
  We recruited patients with decompensated cirrhosis (n=69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolar-arterial oxygen gradient (AaDO2) ≥15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient ≥25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study.
  
  
  RESULTS
  Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p=0.037) and higher oxidative index values (p=0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p=0.049). The potential POPH patients exhibited elevated AaDO2, suggesting the presence of pulmonary shunting.
  
  
  CONCLUSIONS
  Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Terao
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.forename: Naofumi
authors.initials: N
authors.lastname: Tamaki
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Nakamura
authors.forename: Takaaki
authors.initials: T
authors.lastname: Tomofuji
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Umeda
authors.forename: Susumu
authors.initials: S
authors.lastname: Shinoura
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yoshida
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nouso
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ekuni
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koike
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.forename: Manabu
authors.initials: M
authors.lastname: Morita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020065:Hepatopulmonary Syndrome / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects; D008168:Lung / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D014664:Vasodilation