Luis Téllez, Jesús Donate, Antonio Guerrero, Idoia Agulleiro Beraza, Diego San Martín, Edilmar Alvarado, Victor Echevarría, Ángela Puente, Javier Zamora, Susana Del Prado, Andrés Tenes, Guillem Balagué, Barbara Vidal, Cristina Geli, Miguel Ángel Rodríguez-Gandía, Anna Baiges, Anna Brujats, Daniel Lopéz-Herrera Rodríguez, Santiago Fernández-Gordón Sánchez, José Ignacio Fortea, Maria Jesús Del Cerro, Candid Villanueva, Juan Carlos García-Pagán, Álvaro Giráldez, Agustín Albillos
Hospital Universitario Ramón y Cajal and Universidad de Alcalá. Hospital Universitario Virgen del Rocío and University of Seville. Universitat de Barcelona. Hospital Santa Creu i Sant and Autonomous University of Barcelona. Marqués de Valdecilla University Hospital. University of Birmingham.
Spain and United Kingdom
Journal of Hepatology
J Hepatol 2025;
DOI: 10.1016/j.jhep.2025.09.011
Abstract
Background & aims: Portopulmonary hypertension (PoPH) is a severe complication of cirrhosis and portal hypertension. In 2022, the European Task Force revised the diagnostic criteria for pulmonary arterial hypertension (PAH), defining early stages by a mean pulmonary arterial pressure (mPAP) of 20.5-24.5 mmHg and pulmonary vascular resistance (PVR) >2 Wood units. We evaluated the predictive prognostic value of these revised criteria in cirrhotic patients.
Methods: In this longitudinal, multicenter, observational cohort, 428 adults with cirrhosis and portal hypertension underwent right-heart catheterization between 2015 and 2023 and were stratified into five groups: normal, early-PoPH, classic-PoPH, post-capillary pulmonary hypertension, and unclassified profiles. All-cause mortality was analyzed by multivariable Cox regression and competing-risk models, with liver transplantation as an intercurrent event.
Results: Over a median follow-up time of 20.0 months (IQR 8.0 -36.0), three-year survival rates were 76.7%, 49.5%, and 42.0% in the normal mPAP, early-PoPH, and classic-PoPH, respectively. After adjustment for age, sex, liver function, and portal-hypertension severity, both early-PoPH (HR 3.5 [1.9 -6.3], p <0.01) and classic-PoPH (HR 4.5 [2.6 -7.6], p <0.01) remained independent predictors of mortality versus normal mPAP; these associations persisted in competing-risk analysis, whereas post-capillary pulmonary hypertension and unclassified groups did not differ from the normal mPAP cohort.
Conclusion: Applying the 2022 ESC/ERC definitions of PAH identifies a subset of patients with cirrhosis with early-stage PoPH, characterized by mild pulmonary vascular resistance elevation, who nevertheless face a markedly increased risk of death, emphasizing the need for systematic screening and early targeted intervention.
Impact and implications: Portopulmonary hypertension (PoPH) is a severe and often overlooked complication of cirrhosis. Using the updated 2022 ESC/ERS diagnostic criteria, this multicenter study identified a previously unrecognized subgroup of cirrhotic patients with early-stage PoPH, defined by mildly elevated pulmonary vascular resistance and mean pulmonary artery pressure. Despite their subtle hemodynamic changes, these patients showed significantly reduced survival, independent of liver disease severity. These results highlight the prognostic relevance of early PoPH and suggest that applying the new criteria may help refine risk stratification and guide closer follow-up or earlier consideration of targeted interventions in selected patients.
Category
Class I. Pulmonary Hypertension Associated with Liver Disease
Age Focus: Adult Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
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