Abstract / Summary
Pulmonary arterial hypertension (PAH) is increasingly recognized as a systemic disorder. Liver involvement in PAH is common, ranging from subclinical cholestatic abnormalities and impaired synthetic function to congestive hepatopathy and cardiac cirrhosis, and these changes closely mirror right-sided filling pressures, hemodynamic severity, and clinical outcomes. Non-invasive tools such as liver stiffness measurement and fibrosis indices integrate reversible congestion and chronic fibrotic burden, identify distinct “cardiohepatic” phenotypes, and provide prognostic information that complements traditional cardiopulmonary markers. Experimental and translational data indicate that hepatic congestion, inflammation, metabolic stress, and impaired detoxification can feed back on the pulmonary vasculature and right ventricle through cytokines, bile acids, metabolites, and gut-derived products, supporting a bidirectional liver–heart–lung axis rather than a one-way consequence of right heart failure. Conversely, chronic liver disease and portal hypertension can drive pulmonary vascular remodeling and portopulmonary hypertension via hyperdynamic circulation, portosystemic shunting, and a vasoactive, pro-inflammatory milieu, further underscoring the dual “PAH-to-liver” and “liver-to-pulmonary circulation” pathways. Recognition and systematic assessment of hepatic involvement should therefore be integrated into PAH risk stratification and management, including routine liver biochemistry, non-invasive fibrosis and congestion markers, imaging, and close collaboration with hepatology, while future studies aim to refine axis-based prognostic models and explore liver-directed or liver-attentive therapeutic strategies. The liver–heart–lung axis in pulmonary arterial hypertension. Pulmonary Arterial Hypertension (PAH) drives pulmonary vascular remodelling with increased Pulmonary Vascular Resistance (PVR), imposing Right Ventricular (RV) pressure overload. Progressive RV dysfunction elevates right atrial/central venous pressures, promoting hepatic venous congestion and reduced effective perfusion, which together contribute to congestive hepatopathy characterized by cholestasis, increasing fibrosis/stiffness, and impaired synthetic function. In turn, hepatic signalling—including inflammatory mediators, bile acids and other metabolites, and gut-derived factors—may exacerbate pulmonary vascular remodelling and accelerate RV decompensation, forming a bidirectional feed-forward loop. Separately, liver disease with portal hypertension can precipitate Portopulmonary Hypertension (PoPH) through hyperdynamic circulation, portosystemic shunting and vasoactive–inflammatory pathways, further increasing PVR. Clinically, integrating hepatic biochemistry, coagulation/synthetic indices, and non-invasive assessmentmay refine PAH risk stratification and longitudinal monitoring.