Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study

Abstract

Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 +/- 0.02, 1.02 +/- 0.18, 2.86 +/- 0.77, and 6.56 +/- 1.46 EU/mL, p < 0.001) and LBP (7026 +/- 3336, 11,445 +/- 1247, 11,947 +/- 1164, and 13,791 +/- 2032 ng/mL, p = 0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83 +/- 0.17, 2.62 +/- 0.22, 3.69 +/- 0.28, and 4.29 +/- 0.34 pg/mL, p < 0.001), demonstrating a significant difference between each grade (p < 0.05). HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS.