Laurent Savale1, Manuel Guimas2, Nathan Ebstein3, Marie Fertin4, Mitja Jevnikar5, Sébastien Renard6, Delphine Horeau-Langlard7, Cécile Tromeur8, Céline Chabanne9, Grégoire Prevot10, Ari Chaouat11, Pamela Moceri12, Élise Artaud-Macari13, Bruno Degano14, Romain Tresorier15, Clément Boissin16, Hélène Bouvaist17, Anne-Claire Simon18, Marianne Riou19, Nicolas Favrolt20, Sylvain Palat21, Delphine Bourlier22, Pascal Magro23, Vincent Cottin24, Emmanuel Bergot2, Nicolas Lamblin4, Xavier Jaïs5, Audrey Coilly25, François Durand26, Claire Francoz26, Filomena Conti27, Philippe Hervé5, Gérald Simonneau5, David Montani5, Jean-Charles Duclos-Vallée25, Didier Samuel25, Marc Humbert5, Pascal De Groote4, Olivier Sitbon5. 1. Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France; AP-HP, Service de pneumologie, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France. Electronic address: laurent.savale@aphp.fr. 2. Service de Pneumologie, CHRU Côte de Nacre, 14033 Caen, France. 3. Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France; AP-HP, Service de pneumologie, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin Bicêtre, France. 4. Université de Lille, Service de cardiologie, CHU Lille, Institut Pasteur de Lille, Inserm U1167, F-59000, Lille, France. 5. Université Paris-Saclay, Faculté de Médecine, Le Kremlin Bicêtre, France; AP-HP, Service de pneumologie, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin Bicêtre, France; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France. 6. Département de cardiologie, Hôpital La Timone, Aix-Marseille Université, Marseille, France. 7. Service de pneumologie, CHU de Nantes, Hôpital Laënnec, Nantes, France. 8. European Brittany University, Brest, France; Department of Internal Medicine and Chest Diseases, University Hospital Centre La Cavale Blanche, Brest, France; Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), EA 3878, CIC INSERM 1412, Brest, France. 9. Département de cardiologie et maladies vasculaires, CHU de Rennes - Hôpital Pontchaillou, Rennes, France. 10. CHU de Toulouse, Hôpital Larrey, Service de pneumologie, Toulouse, France. 11. Université de Lorraine; Département de pneumologie, CHRU de Nancy; Inserm U1116, Vandœuvre-lès-Nancy, France. 12. Service de cardiologie, Centre Hospitalier Universitaire de Nice-Hôpital Pasteur, Nice, France. 13. Département de pneumologie, Hôpital universitaire, Rouen, France. 14. Service de pneumologie, CHRU, Besançon, France. 15. Service de cardiologie, Hôpital Gabriel Montpied, CHU, Clermont-Ferrand, France. 16. Service de pneumologie, Hôpital universitaire, Montpellier, France. 17. Hôpital La Tronche, Service de cardiologie, CHU de Grenoble-Alpes, Grenoble, France. 18. Service de pneumologie, CHU Poitiers, Poitiers, France. 19. Service de pneumologie, nouvel hôpital civil, hôpitaux universitaires, Strasbourg, France. 20. Service de pneumologie, CHU, Dijon, France. 21. Service de pneumologie, CHRU, Limoges, France. 22. Service des maladies respiratoires, hôpital Haut-Lévêque, CHU de Bordeaux, Pessac, France. 23. Service de pneumologie, CHRU de Tours, Tours, France. 24. Université Claude-Bernard Lyon 1, hôpital Louis-Pradel, service de pneumologie, Centre de référence national des maladies pulmonaires rares, UMR154, 69677 Lyon, France. 25. AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif; UMR-S 1193, Université Paris-Saclay; DHU HEPATINOV, Villejuif, France. 26. Inserm, U1149, Centre de Recherche sur l'Inflammation (CRI) UMRS1149, Université de Paris, AP-HP, Service d'hépatologie, Hôpital Beaujon, Clichy, France. 27. Sorbonne Université, UPMC, Inserm, UMR_S 938 "Centre de Recherche Saint-Antoine", Paris, France; AP-HP, Pitié-Salpêtrière Hospital, Unité Médicale de Transplantation Hépatique, Paris, France.
Abstract
BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
BACKGROUND & AIMS: Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. METHODS: Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. RESULTS: Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9-15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p <0.001), 6-minute walk distance (6MWD) (p <0.0001) and pulmonary vascular resistance (p <0.0001). Overall survival rates were 84%, 69% and 51% at 1, 3 and 5 years, respectively. Baseline 6MWD, sex, age and MELD score or Child-Pugh stage were identified as independent prognostic factors. Survival from PoPH diagnosis was significantly better in the subgroup of patients who underwent liver transplantation (92%, 83% and 81% at 1, 3 and 5 years, respectively). CONCLUSION: Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. LAY SUMMARY: Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.
Authors: Manik Aggarwal; Manshi Li; Abhishek Bhardwaj; William D Wallace; Xiaofeng Wang; William D Carey; Raed A Dweik; Gustavo A Heresi; Adriano R Tonelli Journal: Eur J Gastroenterol Hepatol Date: 2022-04-01 Impact factor: 2.566
Authors: Hilary M DuBrock; James R Runo; Corey J Sadd; Charles D Burger; Rodrigo Cartin-Ceba; Charles B Rosen; Timucin Taner; Scott L Nyberg; Julie K Heimbach; James Y Findlay; Michael J Krowka Journal: Transplant Direct Date: 2020-11-10
Authors: Arun Jose; Shimul A Shah; Nadeem Anwar; Courtney R Jones; Kenneth E Sherman; Jean M Elwing Journal: Liver Transpl Date: 2021-06-29 Impact factor: 6.112
Authors: Sandeep Sahay; Sami Al Abdi; Celia Melillo; Jennie Newman; Raed A Dweik; Gustavo A Heresi; Adriano R Tonelli Journal: Transplant Direct Date: 2021-06-08