The Importance of Liver‐Lung Communication in Pulmonary Vascular Diseases

In normal health, the liver and lungs enjoy a close anatomic, physiologic, and functional relationship. In the context of pulmonary vascular disease, however, there is accumulating evidence that the interplay between the gut microbiome, hepatic system, and pulmonary vasculature (so-called "gut-liver-lung" axis) plays an important role in driving disease pathogenesis and determining clinical outcomes. Despite recognizing the importance of the gut-liver-lung axis in pulmonary vascular disease however, little is known about the clinical characteristics, circulating factors, and physiologic pathways that mediate this important axis of communication. In this clinical and translationally focused review, we provide an overview of liver-lung communication in normal physiology, and contrast this with gut-liver-lung derangements in pulmonary arterial hypertension, portopulmonary hypertension, and hepatopulmonary syndrome. We conclude with identifying key gaps in knowledge that will need to be addressed in order to manipulate the gut-liver-lung axis to prevent worsening pulmonary vascular disease, develop novel therapeutics, and improve patient outcomes.