Conflicts of interest: No conflicts of interest exist for either of the authors of this manuscript.
Advances in Clinical Practice
Hepatopulmonary syndrome: Update on recent advances in pathophysiology, investigation, and treatment
Article first published online: 22 JAN 2013
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 28, Issue 2, pages 213–219, February 2013
How to Cite
Grace, J. A. and Angus, P. W. (2013), Hepatopulmonary syndrome: Update on recent advances in pathophysiology, investigation, and treatment. Journal of Gastroenterology and Hepatology, 28: 213–219. doi: 10.1111/jgh.12061
- Issue published online: 22 JAN 2013
- Article first published online: 22 JAN 2013
- Accepted manuscript online: 28 NOV 2012 07:17AM EST
- Manuscript Accepted: 11 OCT 2012
- hepatopulmonary syndrome;
- nitric oxide;
Hepatopulmonary syndrome (HPS) is an important cause of dyspnea and hypoxia in the setting of liver disease, occurring in 10–30% of patients with cirrhosis. It is due to vasodilation and angiogenesis in the pulmonary vascular bed, which leads to ventilation-perfusion mismatching, diffusion limitation to oxygen exchange, and arteriovenous shunting. There is evidence, primarily from animal studies, that vasodilation is mediated by a number of endogenous vasoactive molecules, including endothelin-1 and nitric oxide (NO). In experimental HPS, liver injury stimulates release of endothelin-1 and results in increased expression of ETB receptors on pulmonary endothelial cells, leading to upregulation of endothelial NO synthase (eNOS) and subsequent increased production of NO, which causes vasodilation. In addition, increased phagocytosis of bacterial endotoxin in the lung not only promotes stimulation of inducible NO synthase, which increases NO production, but also contributes to intrapulmonary accumulation of monocytes, which may stimulate angiogenesis via vascular endothelial growth factor pathway. Despite these insights into the pathogenesis of experimental HPS, there is no established medical therapy, and liver transplantation remains the main treatment for symptomatic HPS, although selected patients may benefit from other surgical or radiological interventions. In this review, we focus on recent advances in our understanding of the pathophysiology of HPS, and discuss current approaches to the investigation and treatment of this condition.