Portopulmonary Hypertension: Current Developments and Future Perspectives

Overview

Journal Liver Res

Date 2025 Feb 17

PMID 39959808

Authors

Huawei Xu

Baoquan Cheng

Renren Wang

Mengmeng Ding

Yanjing Gao

Affiliations

Soon will be listed here.

Abstract

Portopulmonary hypertension (POPH) is a severe pulmonary vascular disease secondary to portal hypertension and a subset of Group 1 pulmonary hypertension (PH). The pathological changes of POPH are indistinguishable from other PH phenotypes, including endothelial dysfunction, pulmonary vasoconstriction, and vascular remodeling. These changes cause a progressive increase in pulmonary vascular resistance and afterload of the right ventricle, eventually leading to severe right heart failure. The prognosis of POPH is extremely poor among untreated patients. POPH is associated with a high risk of death after liver transplantation (LT), and severe POPH is considered an absolute contraindication for LT. However, pulmonary arterial hypertension (PAH)-targeted therapies are administered to patients with POPH, and aggressive drug treatment significantly optimizes pulmonary hemodynamics and reduces the risk of death. Therefore, early diagnosis, aggressive PAH-targeted therapies, and proper selection of liver transplant candidates are vital to reduce the risk of surgery and improve clinical outcomes. This article aims to review the results of previous studies and describe biological mechanisms, epidemiology, potential risk factors, and diagnostic approaches of POPH. Moreover, we introduce recent therapeutic interventions for the early diagnosis of POPH and efficient clinical management decisions.

References

McLaughlin V, Oudiz R, Frost A, Tapson V, Murali S, Channick R . Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2006; 174(11):1257-63. DOI: 10.1164/rccm.200603-358OC. View

Le Pavec J, Souza R, Herve P, Lebrec D, Savale L, Tcherakian C . Portopulmonary hypertension: survival and prognostic factors. Am J Respir Crit Care Med. 2008; 178(6):637-43. DOI: 10.1164/rccm.200804-613OC. View

Raevens S, De Pauw M, Reyntjens K, Geerts A, Verhelst X, Berrevoet F . Oral vasodilator therapy in patients with moderate to severe portopulmonary hypertension as a bridge to liver transplantation. Eur J Gastroenterol Hepatol. 2012; 25(4):495-502. DOI: 10.1097/MEG.0b013e32835c504b. View

Jose A, Kher A, ODonnell R, Elwing J . Cardiac magnetic resonance imaging as a prognostic biomarker in treatment-naïve pulmonary hypertension. Eur J Radiol. 2019; 123:108784. DOI: 10.1016/j.ejrad.2019.108784. View

Giusca S, Jinga M, Jurcut C, Jurcut R, Serban M, Ginghina C . Portopulmonary hypertension: from diagnosis to treatment. Eur J Intern Med. 2011; 22(5):441-7. DOI: 10.1016/j.ejim.2011.02.018. View

Li W, Long L, Yang X, Tong Z, Southwood M, King R . Circulating BMP9 Protects the Pulmonary Endothelium during Inflammation-induced Lung Injury in Mice. Am J Respir Crit Care Med. 2020; 203(11):1419-1430. PMC: 8456542. DOI: 10.1164/rccm.202005-1761OC. View

Kemp K, Savale L, OCallaghan D, Jais X, Montani D, Humbert M . Usefulness of first-line combination therapy with epoprostenol and bosentan in pulmonary arterial hypertension: an observational study. J Heart Lung Transplant. 2011; 31(2):150-8. DOI: 10.1016/j.healun.2011.11.002. View

Reichenberger F, Voswinckel R, Steveling E, Enke B, Kreckel A, Olschewski H . Sildenafil treatment for portopulmonary hypertension. Eur Respir J. 2006; 28(3):563-7. DOI: 10.1183/09031936.06.00030206. View

Hoeper M, Al-Hiti H, Benza R, Chang S, Corris P, Gibbs J . Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2021; 9(6):573-584. DOI: 10.1016/S2213-2600(20)30532-4. View

10.

Elliott C, Barst R, Seeger W, Porres-Aguilar M, Brown L, Zamanian R . Worldwide physician education and training in pulmonary hypertension: pulmonary vascular disease: the global perspective. Chest. 2010; 137(6 Suppl):85S-94S. DOI: 10.1378/chest.09-2816. View

11.

Haraldsson A, Wadenvik H, Ricksten S . Inhaled prostacyclin and platelet function after cardiac surgery and cardiopulmonary bypass. Intensive Care Med. 2000; 26(2):188-94. DOI: 10.1007/s001340050044. View

12.

Nagasue N, Dhar D, Yamanoi A, Emi Y, Udagawa J, Yamamoto A . Production and release of endothelin-1 from the gut and spleen in portal hypertension due to cirrhosis. Hepatology. 2000; 31(5):1107-14. DOI: 10.1053/he.2000.6596. View

13.

DuBrock H, Cartin-Ceba R, Channick R, Kawut S, Krowka M . Sex Differences in Portopulmonary Hypertension. Chest. 2020; 159(1):328-336. PMC: 7893306. DOI: 10.1016/j.chest.2020.07.081. View

14.

Ishikawa T, Egusa M, Kawamoto D, Nishimura T, Sasaki R, Saeki I . Screening for portopulmonary hypertension using computed tomography-based measurements of the main pulmonary artery and ascending aorta diameters in patients with portal hypertension. Hepatol Res. 2021; 52(3):255-268. DOI: 10.1111/hepr.13735. View

15.

Salgia R, Goodrich N, Simpson H, Merion R, Sharma P . Outcomes of liver transplantation for porto-pulmonary hypertension in model for end-stage liver disease era. Dig Dis Sci. 2014; 59(8):1976-82. PMC: 4119507. DOI: 10.1007/s10620-014-3065-y. View

16.

Badesch D, Raskob G, Elliott C, Krichman A, Farber H, Frost A . Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. Chest. 2009; 137(2):376-87. DOI: 10.1378/chest.09-1140. View

17.

BUSSE GRAWITZ P . [The course of inflammation in connective tissue]. Virchows Arch Pathol Anat Physiol Klin Med. 1952; 322(4):381-96. DOI: 10.1007/BF00957586. View

18.

Raevens S, Colle I, Reyntjens K, Geerts A, Berrevoet F, Rogiers X . Echocardiography for the detection of portopulmonary hypertension in liver transplant candidates: an analysis of cutoff values. Liver Transpl. 2013; 19(6):602-10. DOI: 10.1002/lt.23649. View

19.

Fix O, Bass N, De Marco T, Merriman R . Long-term follow-up of portopulmonary hypertension: effect of treatment with epoprostenol. Liver Transpl. 2007; 13(6):875-85. DOI: 10.1002/lt.21174. View

20.

Raevens S, Geerts A, Van Steenkiste C, Verhelst X, Van Vlierberghe H, Colle I . Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int. 2015; 35(6):1646-60. DOI: 10.1111/liv.12791. View