A Role for Alveolar Exhaled Nitric Oxide Measurement in the Diagnosis of Hepatopulmonary Syndrome

Goals: The authors sought to characterize predominantly alveolar exhaled nitric oxide (eNO) in hepatopulmonary syndrome (HPS) compared with non-HPS, changes after liver transplantation, and diagnostic properties. Background: HPS is defined by liver disease, intrapulmonary vascular dilatations (IPVDs), and hypoxemia. Rat models and small human studies suggest that NO overproduction may cause IPVDs. Study: A retrospective review of the Canadian HPS Database (2007 to 2017) and prospective eNO measurement (main outcome) in healthy controls (measurement expiratory flow, 200 mL/s). HPS was defined as: (1) liver disease; (2) contrast echocardiography consistent with IPVDs; and (3) partial pressure of arterial oxygen <70 mm Hg with alveolar-arterial gradient >20 mm Hg; subclinical HPS as criteria (1) and (2) only; and no HPS as criterion (1) only. Current smokers and subjects with asthma or pulmonary hypertension were excluded. A linear mixed effects model was used to compare eNO between groups and before and after transplantation. Results: eNO was 10.4±0.7 ppb in HPS (n=26); 8.3±0.6 ppb in subclinical HPS (n=38); 7.1±1.0 ppb in no HPS (n=15); and 5.6±0.7 ppb in controls (n=30) ( P <0.001). eNO decreased from 10.9±0.8 ppb preliver to 6.3±0.8 ppb postliver transplant (n=6 HPS, 6 subclinical HPS) ( P <0.001). eNO <6 ppb was 84.4% (73.1% to 92.2%) sensitive and ≥12 ppb was 78.1% (69.4% to 85.3%) specific for HPS (vs. subclinical HPS). Conclusions: HPS subjects have higher alveolar eNO than non-HPS subjects, levels normalize with liver transplantation. Applying eNO cutoff values may aid in HPS diagnosis.