Hepatopulmonary syndrome: Update on recent advances in pathophysiology, investigation, and treatment

Abstract

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 ventilationperfusion 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.

Hepatopulmonary syndrome and liver transplantation: the review and a case report

“…ГПС различных стадий встречается среди пациентов с циррозом печени с частотой от 10 до 30% [10][11][12].…”

Hepatopulmonary Syndrome: A Brief Review

“…Moreover, many studies have failed to establish a clear link between the severity of liver disorder and the presence of HPS. Consequently, clinical symptoms such as dyspnea, cyanosis, digital clubbing, orthodeoxia, and platypnea will have more diagnostic value in establishing a more reliable definition [5,6].…”

“…Blood gas analysis showed an increase of age-regulated A-a PO 2 with or without hypoxemia. In addition, chest radiograph and other pulmonary function tests have to be done in order to exclude other possible pulmonary cause [1,2,6,17]. The screening modalities used to assess IPVD are MTTE and technetium-labeled macroaggregated albumin (MAA) scan.…”

“…This event could occur in portal hypertension, which will eventually result in intestines perfusion disturbance and increased rate of gram-negative bacteria and enteral endotoxin translocation. Moreover, it also induced the release of vasoactive mediators including NO [1,6,8,9].…”

Molecular mechanisms of hepatopulmonary syndrome

“…Today the term "hepatopulmonary syndrome" (HPS) describes deficiency of arterial oxygenation caused by dilatation of intrapulmonary vessels associated with liver disease [2][3][4][5]. A classification of the severity of HPS based on oxygenation abnormalities has been proposed [4] (table 1).…”