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. 2013:124:250-62.

The lung in liver disease: old problem, new concepts

Michael B Fallon  1 , Junlan Zhang
Affiliations

The lung in liver disease: old problem, new concepts

Michael B Fallon et al. Trans Am Clin Climatol Assoc. 2013.

Abstract

Liver dysfunction has been recognized to influence the lung in many different clinical situations, although the mechanisms for these effects are not well understood. One increasingly recognized interaction, the hepatopulmonary syndrome (HPS) occurs in the context of cirrhosis and results when alveolar microvascular dilation causes arterial gas exchange abnormalities and hypoxemia. HPS occurs in up to 30% of patients with cirrhosis and significantly increases mortality in affected patients. Currently, liver transplantation is the only curative therapy. Experimental biliary cirrhosis induced by common bile duct ligation (CBDL) in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and has been contrasted with other experimental models of cirrhosis in which HPS does not develop. Microvascular dilation, intravascular monocyte infiltration, and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Our recent studies have identified biliary epithelium and activation and interaction between the endothelin-1 (ET-1)/endothelial endothelin B (ETB) receptor and CX3CL1/CX3CR1 pathways as important mechanisms for the observed pathologic events. These studies define novel interactions between the lung and liver in cirrhosis and may lead to effective medical therapies.

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Conflict of interest statement

Potential Conflicts of Interest: None disclosed.

Figures

Fig. 1.
Fig. 1.
Animal models of experimental HPS. Left: CK-19 staining of bile duct epithelium in control (A), CBDL (B), TAA (C), and PVL (D) animal livers. Right: HPS changes (intrapulmonary shunt fraction and AaPO2) in each model. *P<0.05 versus control.
Fig. 2.
Fig. 2.
Effects of ET-1 on endothelial cell CX3CL1 /CX3CR1 expression in the presence or absence of BQ788 (ETB receptor antagonist). Left: mRNA levels CX3CL1 and CX3CR1. Right: protein levels. *P<0.05 versus control, ‡ P<0.05 versus ET-1 treatment.
Fig. 3.
Fig. 3.
Working model of the pathogenesis of experimental HPS.
See this image and copyright information in PMC

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