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Baba S, Ogawa E, Akagi K, Matsuda K, Hirata T, Okamoto T, Okajima H, Takita J. Hemodynamic and Clinical Response to Liver Transplantation in Children and Young Adults POPH Patients. Pediatr Cardiol 2024; 45:1142-1150. [PMID: 36754885 DOI: 10.1007/s00246-023-03121-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 01/30/2023] [Indexed: 02/10/2023]
Abstract
Portopulmonary hypertension is an intractable form of pulmonary hypertension. Although liver transplantation is recommended for patients who respond poorly to treatments, the mechanisms by which liver transplantation improves pulmonary hypertension remain unclear. The present study investigated these mechanisms by retrospectively evaluating patients' data. This study retrospectively evaluated echocardiography and catheterization data before and after liver transplantation in 12 patients who underwent liver transplantation from 2001 to 2019. The 12 patients included one male and 11 females, of median age at liver transplantation of 10 years, 2 months. Nine patients underwent liver transplantation for congenital biliary atresia and three for portal vein aplasia or hypoplasia. Mean pulmonary arterial pressure was 44.1 ± 8.1 mmHg at the first cardiac catheter examination, 35.3 ± 7.8 mmHg before liver transplantation, and 29.5 ± 9.3 mmHg 6 months after liver transplantation. Pulmonary artery pressure was reduced by treatments of pulmonary hypertension and by liver transplantation. Pulmonary vascular resistance did not differ before and after liver transplantation, whereas the cardiac index decreased significantly, indicating that the significant reduction in mean pulmonary artery pressure was due to a decrease in cardiac index. Decreased cardiac index was thought to result from improvements in hyperdynamic conditions due to increased (normalized) systemic vascular resistance. Liver transplantation likely suppresses shear stress on pulmonary arteries, preventing further damage by hyper-circulation. A longer-term evaluation is required to determine the effect of improving pulmonary artery remodeling.
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Affiliation(s)
- Shiro Baba
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan.
| | - Eri Ogawa
- Department of Pediatric Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Kentaro Akagi
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Koichi Matsuda
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Takuya Hirata
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Tatsuya Okamoto
- Department of Pediatric Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Hideaki Okajima
- Department of Pediatric Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
| | - Junko Takita
- Department of Pediatrics, Graduate School of Medicine, Kyoto University, 54 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto City, Kyoto, 606-8507, Japan
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McLin VA, Franchi-Abella S, Brütsch T, Bahadori A, Casotti V, de Ville de Goyet J, Dumery G, Gonzales E, Guérin F, Hascoet S, Heaton N, Kuhlmann B, Lador F, Lambert V, Marra P, Plessier A, Quaglia A, Rougemont AL, Savale L, Sarma MS, Sitbon O, Superina RA, Uchida H, van Albada M, van der Doef HPJ, Vilgrain V, Wacker J, Zwaveling N, Debray D, Wildhaber BE. Expert management of congenital portosystemic shunts and their complications. JHEP Rep 2024; 6:100933. [PMID: 38234409 PMCID: PMC10792643 DOI: 10.1016/j.jhepr.2023.100933] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2023] [Revised: 09/18/2023] [Accepted: 09/25/2023] [Indexed: 01/19/2024] Open
Abstract
Congenital portosystemic shunts are often associated with systemic complications, the most challenging of which are liver nodules, pulmonary hypertension, endocrine abnormalities, and neurocognitive dysfunction. In the present paper, we offer expert clinical guidance on the management of liver nodules, pulmonary hypertension, and endocrine abnormalities, and we make recommendations regarding shunt closure and follow-up.
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Affiliation(s)
- Valérie Anne McLin
- Swiss Pediatric Liver Center, Gastroenterology, Hepatology and Pediatric
Nutrition Unit, Department of Pediatrics, Gynecology and Obstetrics, University
of Geneva, Geneva, Switzerland
- ERN RARE LIVER
| | - Stéphanie Franchi-Abella
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- AP-HP, Centre de référence des maladies rares du foie de l’enfant,
Service de radiologie pédiatrique diagnostique et interventionnelle, Hôpital
Bicêtre, Le Kremlin-Bicêtre, France
- BIOMAPS UMR 9011 CNRS, INSERM, CEA, Orsay, France
- ERN RARE LIVER
- ERN Transplant Child
| | | | - Atessa Bahadori
- Department of Pediatrics, Gynecology and Obstetrics, University of
Geneva, Geneva, Switzerland
| | - Valeria Casotti
- ERN Transplant Child
- Pediatric Hepatology, Gastroenterology and Transplant Centre, ASST Papa
Giovanni XXIII Hospital, Bergamo, Italy
| | - Jean de Ville de Goyet
- Pediatric Department for the Treatment and Study of Abdominal Diseases
and Abdominal Transplantation, ISMETT UPMC, Palermo, Italy
| | - Grégoire Dumery
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- AP-HP, Service de gynécologie et d’obstétrique, Hôpital Bicêtre, Le
Kremlin-Bicêtre, France
| | - Emmanuel Gonzales
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- ERN RARE LIVER
- ERN Transplant Child
- AP-HP, Centre de référence des maladies rares du foie de l’enfant, FHU
Hepatinov, Service d’hépatologie et transplantation hépatique pédiatriques,
Hôpital Bicêtre, Le Kremlin-Bicêtre, France
- INSERM UMRS_1193, Orsay, France
| | - Florent Guérin
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- ERN RARE LIVER
- ERN Transplant Child
- AP-HP, Service de chirurgie pédiatrique, Hôpital Bicêtre, Le
Kremlin-Bicêtre, France
| | - Sebastien Hascoet
- Department of Congenital Heart Diseases, Hôpital Marie Lannelongue,
France
- INSERM UMR_S 999, Université Paris, France
| | - Nigel Heaton
- Institute of Liver Studies, Kings College Hospital, London,
England
| | - Béatrice Kuhlmann
- Pediatric Endocrinology, Cantonal Hospital Aarau KSA, Aarau,
Switzerland
| | - Frédéric Lador
- Service de Pneumologie, University of Geneva, Geneva,
Switzerland
| | - Virginie Lambert
- AP-HP, Centre de référence des maladies rares du foie de l’enfant,
Service de radiologie pédiatrique diagnostique et interventionnelle, Hôpital
Bicêtre, Le Kremlin-Bicêtre, France
- Cardiologie congénitale, Institut Mutualiste Montsouris, Paris,
France
| | - Paolo Marra
- Department of Radiology, Papa Giovanni XXIII Hospital, School of Medicine
and Surgery - University of Milano-Bicocca, Bergamo, Italy
| | - Aurélie Plessier
- ERN RARE LIVER
- Centre de référence des maladies vasculaires du foie, Service
d’hépatologie Hôpital Beaujon, Clichy, France
- VALDIG
| | - Alberto Quaglia
- Department of Cellular Pathology, Royal Free London NHS Foundation
Trust/UCL Cancer Institute, London, England
| | - Anne-Laure Rougemont
- Swiss Pediatric Liver Center, Division of Clinical Pathology, Diagnostic
Department, University of Geneva, Geneva, Switzerland
| | - Laurent Savale
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- AP-HP, Centre de référence de l’hypertension pulmonaire, Service de
pneumologie et soins intensifs respiratoires, Hôpital Bicêtre, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson,
France
- ERN Lung
| | - Moinak Sen Sarma
- Department of Pediatric Gastroenterology, Sanjay Gandhi Postgraduate
Institute of Medical Sciences, Lucknow, India
| | - Olivier Sitbon
- Université Paris-Saclay, Faculté de médecine, Le Kremlin-Bicêtre,
France
- AP-HP, Centre de référence de l’hypertension pulmonaire, Service de
pneumologie et soins intensifs respiratoires, Hôpital Bicêtre, Le
Kremlin-Bicêtre, France
- INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson,
France
- ERN Lung
| | - Riccardo Antonio Superina
- Northwestern University Feinberg School of Medicine, Ann & Robert H.
Lurie Children’s Hospital of Chicago, Chicago, Illinois, USA
| | - Hajime Uchida
- Organ Transplantation Center, National Center for Child Health and
Development, Tokyo, Japan
| | - Mirjam van Albada
- Department of paediatric and congenital cardiology, University Medical
Center Groningen, University of Groningen, The Netherlands
| | - Hubert Petrus Johannes van der Doef
- Division of paediatric gastroenterology and hepatology, Department of
paediatrics, University Medical Center Groningen, Groningen, The
Netherlands
| | - Valérie Vilgrain
- ERN RARE LIVER
- VALDIG
- Université Paris Cité, CRI, INSERM, Paris, France
- AP-HP, Département de Radiologie, Hôpital Beaujon. Nord, Clichy,
France
| | - Julie Wacker
- Pediatric Cardiology Unit, Department of pediatrics, Gynecology and
Obstetrics, University of Geneva, Geneva, Switzerland
- Centre Universitaire Romand de Cardiologie et Chirurgie Cardiaque
Pédiatrique, University of Geneva and Lausanne, Switzerland
| | - Nitash Zwaveling
- Department of Pediatric Endocrinology, Amsterdam University Medical
Centers, University of Amsterdam, Amsterdam, The Netherlands
| | - Dominique Debray
- ERN RARE LIVER
- ERN Transplant Child
- AP-HP, Unité d’hépatologie pédiatrique et transplantation hépatique,
Hôpital Necker, Paris, France
- Centre de Référence des maladies rares du foie de l’enfant, FILFOIE,
France
| | - Barbara Elisabeth Wildhaber
- ERN RARE LIVER
- Swiss pediatric Liver Center, Division of pediatric surgery, Department
of Pediatrics, Gynecology, and Obstetrics, University of Geneva, Geneva,
Switzerland
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Jasso-Baltazar EA, Peña-Arellano GA, Aguirre-Valadez J, Ruiz I, Papacristofilou-Riebeling B, Jimenez JV, García-Carrera CJ, Rivera-López FE, Rodriguez-Andoney J, Lima-Lopez FC, Hernández-Oropeza JL, Díaz JAT, Kauffman-Ortega E, Ruiz-Manriquez J, Hernández-Reyes P, Zamudio-Bautista J, Rodriguez-Osorio CA, Pulido T, Muñoz-Martínez S, García-Juárez I. Portopulmonary Hypertension: An Updated Review. Transplant Direct 2023; 9:e1517. [PMID: 37492078 PMCID: PMC10365198 DOI: 10.1097/txd.0000000000001517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 05/30/2023] [Accepted: 06/01/2023] [Indexed: 07/27/2023] Open
Abstract
Portal hypertension may have major consequences on the pulmonary vasculature due to the complex pathophysiological interactions between the liver and lungs. Portopulmonary hypertension (PoPH), a subset of group 1 pulmonary hypertension (PH), is a serious pulmonary vascular disease secondary to portal hypertension, and is the fourth most common subtype of pulmonary arterial hypertension. It is most commonly observed in cirrhotic patients; however, patients with noncirrhotic portal hypertension can also develop it. On suspicion of PoPH, the initial evaluation is by a transthoracic echocardiogram in which, if elevated pulmonary pressures are shown, patients should undergo right heart catheterization to confirm the diagnosis. The prognosis is extremely poor in untreated patients; therefore, management includes pulmonary arterial hypertension therapies with the aim of improving pulmonary hemodynamics and moving patients to orthotopic liver transplantation (OLT). In this article, we review in detail the epidemiology, pathophysiology, process for diagnosis, and most current treatments including OLT and prognosis in patients with PoPH. In addition, we present a diagnostic algorithm that includes the current criteria to properly select patients with PoPH who are candidates for OLT.
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Affiliation(s)
- Erick A. Jasso-Baltazar
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Gonzalo A. Peña-Arellano
- Department of Gastroenterology, Instituto de Seguridad Social del Estado de México y Municipios, Mexico State, Mexico
| | | | - Isaac Ruiz
- Departament of Hepatology and Liver Trasplantation, Centre Hospitalier de I´Universite of Montréal, Montreal, Canada
| | - Bruno Papacristofilou-Riebeling
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jose Victor Jimenez
- Department of Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Cristian J. García-Carrera
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Fabián E. Rivera-López
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesús Rodriguez-Andoney
- Pulmonary Circulation Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Francisco C. Lima-Lopez
- Cardiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José Luis Hernández-Oropeza
- Pulmonary Circulation Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Juan A. Torres Díaz
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Eric Kauffman-Ortega
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jesus Ruiz-Manriquez
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Pablo Hernández-Reyes
- Cardiology Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jorge Zamudio-Bautista
- Department of Anesthesiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Carlos A. Rodriguez-Osorio
- Department of Critical Care Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Tomás Pulido
- Cardiopulmonary Department, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico
| | | | - Ignacio García-Juárez
- Department of Gastroenterology and Liver Transplant Unit, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Zhang R, Li T, Shao Y, Bai W, Wen X. Efficacy evaluation of pulmonary hypertension therapy in patients with portal pulmonary hypertension: A systematic review and meta-analysis. Front Pharmacol 2022; 13:991568. [DOI: 10.3389/fphar.2022.991568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 10/26/2022] [Indexed: 11/18/2022] Open
Abstract
Objective: To determine the therapeutic effect of pulmonary arterial hypertension (PAH) agents for portal pulmonary hypertension (POPH).Design: Systematic review and meta-analysis.Background: POPH is a serious complication of end-stage liver disease with a low survival rate. Liver transplantation (LT) is an effective treatment. Due to the presence of POPH, some patients cannot undergo LT. After PAH treatment, patients with POPH can obtain good hemodynamics and cardiac function for LT, but there are no standard guidelines.Methods: Two independent researchers searched PubMed, EMBASE, Cochrane Library, and Web of Science for studies published from inception to 27 September 2022, focusing on the changes in hemodynamics and cardiac function in all patients with POPH to understand the effect of PAH treatment on the entire population of POPH patients. Among these, we specifically analyzed the changes in hemodynamics and cardiac function in moderate and severe POPH patients. After collecting the relevant data, a meta-analysis was carried out using the R program meta-package.Results: A total of 2,775 literatures were retrieved, and 24 literatures were included. The results showed that in all POPH patients (n = 1,046), the following indicators were significantly improved with PAH agents: mPAP: (MD = −9.11 mmHg, p < 0.0001); PVR: (MD = −239.33 dyn·s·cm−5, p < 0.0001); CO: (MD = 1.71 L/min, p < 0.0001); cardiac index: (MD = 0.87 L/(min·m2), p < 0.0001); 6MWD: (MD = 43.41 m, p < 0.0001). In patients with moderate to severe POPH (n = 235), the following indicators improved significantly with PAH agents: mPAP (MD = −9.63 mmHg, p < 0.0001); PVR (MD = −259.78 dyn·s·cm−5, p < 0.0001); CO (MD = 1.76 L/min, p < 0.0001); Cardiac index: (MD = 1.01 L/(min·m2), p = 0.0027); 6MWD: (MD = 61.30 m, p < 0.0001).Conclusion: The application of PAH agents can improve cardiopulmonary hemodynamics and cardiac function in patients with POPH, especially in patients with moderate to severe POPH, and the above changes are more positive.Systematic Review Registration:https://inplasy.com, identifier INPLASY202250034.
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Lv H, Zheng H, Liu J, Cai Q, Ren Y, Yi H, Yang Y, Hu X, Chen G. Expert consensus on liver transplantation perioperative evaluation and rehabilitation for acute-on-chronic liver failure. LIVER RESEARCH 2022; 6:121-129. [PMID: 39958201 PMCID: PMC11791836 DOI: 10.1016/j.livres.2022.08.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 08/15/2022] [Indexed: 11/15/2022]
Abstract
Acute-on-chronic liver failure (ACLF) can be cured by liver transplantation; however, perioperative complications still affect posttransplant outcomes. In recent years, early rehabilitation for critical illness, liver disease, and surgery have significantly improved organ reserve function, surgery tolerance, and postoperative quality of life. They could also be applied in the perioperative period of liver transplantation in patients with ACLF. Therefore, the Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association, the Organ Transplant Committee of China Association Rehabilitation Medicine, and the Guangdong Medical Doctor Association of Organ Transplantation conducted a comprehensive review of rehabilitation in end-stage liver disease, critical illness and surgical patients by summarizing current evidence and best clinical practices and proposed a practice consensus on evaluation of cardiopulmonary and physical function, rehabilitation or physiotherapies, as well as the safety concerns in perioperative liver transplant recipients. It will be a valuable resource for hepatologists, transplant surgeons, and intensivists as they care for ACLF patients during transplantation.
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Affiliation(s)
- Haijin Lv
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Haiqing Zheng
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jianrong Liu
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qing Cai
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yuji Ren
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Huimin Yi
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yang Yang
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiquan Hu
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guihua Chen
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Transplantation Immunology Committee of Branch of Organ Transplantation Physician of Chinese Medical Doctor Association
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Organ Transplant Committee of China Association Rehabilitation Medicine
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Guangdong Medical Doctor Association of Organ Transplantation
- Surgical Intensive Care Unit, Intensive Care Unit of Organ Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Peppas S, Nagraj S, Koutsias G, Kladas M, Archontakis-Barakakis P, Schizas D, Giannakoulas G, Palaiodimos L, Kokkinidis DG. Portopulmonary Hypertension: A Review of the Current Literature. Heart Lung Circ 2022; 31:1191-1202. [PMID: 35667970 DOI: 10.1016/j.hlc.2022.04.056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 04/05/2022] [Accepted: 04/21/2022] [Indexed: 12/20/2022]
Abstract
Portopulmonary hypertension is defined as the development of pulmonary arterial hypertension in the setting of portal hypertension with or without liver cirrhosis. Portal hypertension-associated haemodynamic changes, including hyperdynamic state, portosystemic shunts and splanchnic vasodilation, induce significant alterations in pulmonary vascular bed and play a pivotal role in the pathogenesis of the disease. If left untreated, portopulmonary hypertension results in progressive right heart failure, with a poor prognosis. Although Doppler echocardiography is the best initial screening tool for symptomatic patients and liver transplantation candidates, right heart catheterisation remains the gold standard for the diagnosis of the disease. Severe portopulmonary hypertension exerts a prohibitive risk to liver transplantation by conferring an elevated perioperative mortality risk. It is important for haemodynamic parameters to correspond with non-severe portopulmonary hypertension before patients can proceed with the liver transplantation. Small uncontrolled studies and a recent randomised controlled trial have reported promising results with vasodilatory therapies in clinical and haemodynamic improvement of patients, allowing a proportion of patients to undergo liver transplantation. In this review, the epidemiology, pathogenesis, diagnostic approach and management of portopulmonary hypertension are discussed. We also highlight fields of ongoing investigation pertinent to risk stratification and optimal patient selection to maximise long-term benefit from currently available treatments.
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Affiliation(s)
- Spyros Peppas
- Department of Gastroenterology, Athens Naval Hospital, Athens, Greece.
| | - Sanjana Nagraj
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA; Division of Hospital Medicine, Jacobi Medical Center, Bronx, NY, USA
| | - George Koutsias
- Aristotle University of Thessaloniki, Division of Vascular Surgery, 2(nd) Department of Surgery, Thessaloniki, Greece
| | - Michail Kladas
- Internal Medicine, North Central Bronx Hospital and James J. Peters VA Medical Center, Bronx, NY, USA
| | | | - Dimitrios Schizas
- First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
| | - George Giannakoulas
- Department of Cardiology, AHEPA University Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Leonidas Palaiodimos
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY, USA; Division of Hospital Medicine, Jacobi Medical Center, Bronx, NY, USA
| | - Damianos G Kokkinidis
- Section of Cardiovascular Medicine, Yale University/Yale New Haven Hospital, New Haven, CT, USA
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7
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McGlothlin D, Granton J, Klepetko W, Beghetti M, Rosenzweig EB, Corris P, Horn E, Kanwar M, McRae K, Roman A, Tedford R, Badagliacca R, Bartolome S, Benza R, Caccamo M, Cogswell R, Dewachter C, Donahoe L, Fadel E, Farber HW, Feinstein J, Franco V, Frantz R, Gatzoulis M, Hwa (Anne) Goh C, Guazzi M, Hansmann G, Hastings S, Heerdt P, Hemnes A, Herpain A, Hsu CH, Kerr K, Kolaitis N, Kukreja J, Madani M, McCluskey S, McCulloch M, Moser B, Navaratnam M, Radegran G, Reimer C, Savale L, Shlobin O, Svetlichnaya J, Swetz K, Tashjian J, Thenappan T, Vizza CD, West S, Zuckerman W, Zuckermann A, De Marco T. ISHLT CONSENSUS STATEMENT: Peri-operative Management of Patients with Pulmonary Hypertension and Right Heart Failure Undergoing Surgery. J Heart Lung Transplant 2022; 41:1135-1194. [DOI: 10.1016/j.healun.2022.06.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 06/13/2022] [Indexed: 10/17/2022] Open
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8
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Hayashi R, Kogiso T, Kikuchi N, Yamamoto K, Nakamura S, Egawa H, Hagiwara N, Tokushige K. Portopulmonary hypertension and the risk of high right ventricular systolic pressure in liver transplant candidates. PLoS One 2022; 17:e0267125. [PMID: 35439259 PMCID: PMC9017876 DOI: 10.1371/journal.pone.0267125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2021] [Accepted: 04/02/2022] [Indexed: 12/28/2022] Open
Abstract
Aim Portopulmonary hypertension (PoPH) is a rare and serious complication of liver cirrhosis and portal hypertension that can interfere with liver transplantation (LT). We evaluated the prevalence of PoPH and the clinical features of right ventricular systolic pressure (RVSP), which is equivalent to pulmonary artery systolic pressure, in LT candidates. Methods This was a single-center retrospective study. A total of 157 Japanese patients with decompensated liver cirrhosis or portal hypertension (76 men, median age = 52 years [range: 18–68 years]) were enrolled. The relationships between RVSP and clinical parameters, and the prevalence of PoPH in LT candidates, were evaluated. Results The cardiological parameters were as follows: brain natriuretic peptide (BNP), 39.1 (4.0–780.5) pg/mL; RVSP, 31.2 (16.0–122.4) mmHg; ejection fraction, 58% (28–72%); and mean peak tricuspid regurgitation velocity, 2.3 (1.5–5.3) m/s. The RVSP was significantly higher in females (p = 0.02) and primary biliary cholangitis (PBC) patients (p = 0.01), and was weakly correlated with the BNP level (r = 0.40, p = 0.01). For RVSPs of < 36 and ≥ 36 mmHg, the 5-year survival rates were 36.1% versus 34.1%, and 85.4% versus 85.3%, in non-LT and LT cases, respectively (p = 0.47 and 0.69, respectively). Among six patients with an RVSP ≥ 50 mmHg, three (1.9%) were diagnosed with PoPH and treated with vasodilators. Conclusions PoPH was observed in 3 cases (1.9%) in 157 LT candidates. In patients with suspected mild pulmonary hypertension (RVSP, 36 - 50 mmHg), LT was successfully performed.
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Affiliation(s)
- Ryoko Hayashi
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Tomomi Kogiso
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
- * E-mail:
| | - Noriko Kikuchi
- Department of Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Kana Yamamoto
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shinichi Nakamura
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Hiroto Egawa
- Department of surgery, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Nobuhisa Hagiwara
- Department of Cardiology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Internal Medicine, Institute of Gastroenterology, Tokyo Women’s Medical University, Shinjuku-ku, Tokyo, Japan
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9
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Xu H, Cheng B, Wang R, Ding M, Gao Y. Portopulmonary hypertension: Current developments and future perspectives. LIVER RESEARCH 2022; 6:10-20. [PMID: 39959808 PMCID: PMC11791819 DOI: 10.1016/j.livres.2022.02.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/08/2022] [Accepted: 02/27/2022] [Indexed: 12/19/2022]
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.
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Affiliation(s)
- Huawei Xu
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Baoquan Cheng
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Renren Wang
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Mengmeng Ding
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
| | - Yanjing Gao
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong, China
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10
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Causes and Circumstances of Death in Portopulmonary Hypertension. Transplant Direct 2021; 7:e710. [PMID: 34124346 PMCID: PMC8191691 DOI: 10.1097/txd.0000000000001162] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 03/30/2021] [Accepted: 03/31/2021] [Indexed: 11/25/2022] Open
Abstract
The causes and circumstances surrounding death are poorly studied in patients with portopulmonary hypertension (PoPH). We sought to determine the specific reasons for dying and characteristics surrounding this process in patients with PoPH.
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11
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Deroo R, Trépo E, Holvoet T, De Pauw M, Geerts A, Verhelst X, Colle I, Van Vlierberghe H, Fallon MB, Raevens S. Vasomodulators and Liver Transplantation for Portopulmonary Hypertension: Evidence From a Systematic Review and Meta-Analysis. Hepatology 2020; 72:1701-1716. [PMID: 32017176 DOI: 10.1002/hep.31164] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 01/20/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Untreated portopulmonary hypertension (PoPH) carries a poor prognosis. Previous reports have described vasomodulator (VM) therapy and liver transplantation (LT) as treatment options. We aimed to provide summary estimates on the endpoints of pulmonary hemodynamics and survival in patients with PoPH, treated with different modalities. APPROACH AND RESULTS We performed a systematic review with meta-analysis of mainly observational and case-control studies describing no treatment, VM, LT, or VM + LT in patients with PoPH. Twenty-six studies (1,019 patients) were included. Both VM and VM + LT improve pulmonary hemodynamics. A substantial proportion of patients treated with VM become eligible for LT (44%; 95% confidence interval [CI], 31-58). Pooled estimates for 1-, and 3-year postdiagnosis survival in patients treated with VM were 86% (95% CI, 81-90) and 69% (95% CI, 50-84) versus 82% (95% CI, 52-95) and 67% (95% CI, 53-78) in patients treated with VM + LT. Of note, studies reporting on the effect of VM mainly included Child-Pugh A/B patients, whereas studies reporting on VM + LT mainly included Child-Pugh B/C. Seven studies (238 patients) included both patients who received VM only and patients who received VM + LT. Risk of death in VM-only-treated patients was significantly higher than in patients who could be transplanted as well (odds ratio, 3.5; 95% CI, 1.4-8.8); however, importantly, patients who proceeded to transplant had been selected very strictly. In 50% of patients, VM can be discontinued post-LT (95% CI, 38-62). CONCLUSIONS VM and VM + LT both improve pulmonary hemodynamics and prognosis in PoPH. In a strictly selected subpopulation of cases where LT is indicated based on severe liver disease and where LT is considered safe and feasible, treatment with VM + LT confers a better prognosis. Considering successful VM, 44% can proceed to LT, with half being able to postoperatively stop medication.
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Affiliation(s)
- Rebecca Deroo
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Eric Trépo
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, C.U.B. Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium.,Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium
| | - Tom Holvoet
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Michel De Pauw
- Department of Cardiology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Isabelle Colle
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Michael B Fallon
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, AZ
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
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12
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Clinical Outcomes after Liver Transplantation in Patients with Portopulmonary Hypertension. Transplantation 2020; 105:2283-2290. [PMID: 33065725 DOI: 10.1097/tp.0000000000003490] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT). METHODS Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in three transplant centers from 1996 to 2019. RESULTS From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pre-transplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1, 3, and 5 year unadjusted survival rates after LT were 72%, 63% and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR 1.91, 95% CI 1.07-3.74, p=0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010. CONCLUSION Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.
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13
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Abstract
PURPOSE OF REVIEW Pulmonary arterial hypertension (PAH) is a disease that carries a significant mortality left untreated. This article aims to review pharmacotherapeutics for PAH. RECENT FINDINGS PAH-specific therapies have evolved over the last three decades and have expanded from one therapy in the 1990s to 14 FDA-approved medications. Current therapies are directed at restoring the imbalance of vasoactive mediators that include nitric oxide, endothelin and prostacyclin. Although these agents are effective as monotherapy, recent trials have promulgated the strategy of upfront combination therapy. The availability of oral prostacyclin agonists has also allowed for expanded treatment options. Risk assessment is vital in guiding therapy for PAH patients. There is ongoing focus on targeting pathological mechanisms of the disease via novel therapies and repurposing existing drugs. SUMMARY There is an array of medications available for the treatment of PAH. Prudent combination of therapies to maximize treatment effect can improve morbidity and mortality. This article reviews the data supporting these therapies and attempts to outline an approach to patient management.
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14
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Weinfurtner K, Forde K. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Current Status and Implications for Liver Transplantation. CURRENT HEPATOLOGY REPORTS 2020; 19:174-185. [PMID: 32905452 PMCID: PMC7473417 DOI: 10.1007/s11901-020-00532-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
PURPOSE OF REVIEW Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are both pulmonary vascular complications of advanced liver disease; however, these syndromes have distinct pathophysiology, clinical implications, and management. RECENT FINDINGS While both conditions are associated with portal hypertension, HPS results from diffuse pulmonary capillary vasodilation and PoPH results from vasoconstriction and vascular remodeling of pulmonary arteries. In HPS, no medical therapies clearly improve outcomes; however, patients have excellent post-LT outcomes with near uniform reversal of hypoxemia. In PoPH, several medical therapies used in idiopathic pulmonary hypertension have been shown improve pulmonary hemodynamics, symptoms, and potentially LT outcomes; however, further study is needed to determine best treatment regimens, long-term outcomes on medical therapy, and role of LT. SUMMARY While HPS results in severe hypoxemia that is usually reversible by LT, PoPH patients develop progressive pulmonary hypertension that may improve with medical therapy.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kimberly Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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15
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Portopulmonary hypertension in the current era of pulmonary hypertension management. J Hepatol 2020; 73:130-139. [PMID: 32145258 DOI: 10.1016/j.jhep.2020.02.021] [Citation(s) in RCA: 82] [Impact Index Per Article: 16.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 02/17/2020] [Accepted: 02/19/2020] [Indexed: 12/21/2022]
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.
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16
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Jha AK, Lata S. Liver transplantation and cardiac illness: Current evidences and future directions. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2020; 27:225-241. [PMID: 31975575 DOI: 10.1002/jhbp.715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Contraindications to liver transplantation are gradually narrowing. Cardiac illness and chronic liver disease may manifest independently or may be superimposed on each other due to shared pathophysiology. Cardiac surgery involving the cardiopulmonary bypass in patients with Child-Pugh Class C liver disease is associated with a high risk of perioperative morbidity and mortality. Liver transplantation involves hemodynamic perturbations, volume shifts, coagulation abnormalities, electrolyte disturbances, and hypothermia, which may prove fatal in patients with cardiac illness depending upon the severity. Additionally, cardiovascular complications are the major cause of adverse postoperative outcomes after liver transplantation even in the absence of cardiac pathologies. Clinical decision-making has remained an unsettled issue in these clinical scenarios. The absence of randomized clinical studies has further crippled our endeavours for a consensus on the management of patients with end-stage liver disease with cardiac illness. This review seeks to address this complex clinical setting by gathering information from published literature. The management algorithm in this review may facilitate clinical decision making and augur future research.
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Affiliation(s)
- Ajay Kumar Jha
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
| | - Suman Lata
- Department of Anesthesiology and Critical Care, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
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17
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Sendra C, Carballo-Rubio V, Sousa JM. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Management in Liver Transplantation in the Horizon 2020. Transplant Proc 2020; 52:1503-1506. [PMID: 32278579 DOI: 10.1016/j.transproceed.2020.02.057] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 02/05/2020] [Indexed: 12/13/2022]
Abstract
Hepatopulmonary syndrome (HPS) is characterized by intrapulmonary microvasculature dilatation that causes intrapulmonary shunting and leads to a gas exchange abnormality in the presence of liver diseases, which is the most common cause of respiratory insufficiency in these patients. HPS doubles the risk of death, and liver transplantation (LT) is the only curative therapeutic option so it should be considered in patients with severe HPS, with excellent survival rates post-LT. However, pretransplant Pao2 <45 mm Hg has been associated with an increase in post-transplant morbidity and mortality, but it does not imply a contraindication for LT. The resolution of HPS usually occurs within 6 months post-LT, but it can take 1 year. Portopulmonary hypertension (PoPH) is defined as pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension with or without liver disease in the absence of other causes of PAH. The prevalence of PoPH is 5% to 10% among liver transplant (LT) candidates. The impact of LT on PoPH is unpredictable. Therefore, despite conferring a high morbidity and mortality, PoPH itself is not an indication for liver transplantation. It may be considered a contraindication for LT in severe cases.
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Affiliation(s)
- Carmen Sendra
- Unit of Digestive Diseases, Virgen del Rocío University Hospital, Sevilla, 41013, Spain
| | | | - Jose Manuel Sousa
- Unit of Digestive Diseases, Virgen del Rocío University Hospital, Sevilla, 41013, Spain.
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18
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Long-term Outcomes and Survival in Moderate-severe Portopulmonary Hypertension After Liver Transplant. Transplantation 2020; 105:346-353. [DOI: 10.1097/tp.0000000000003248] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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19
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Chen XJ, Zhu ZJ, Sun LY, Wei L, Zeng ZG, Liu Y, Qu W, Zhang L. Liver transplantation for severe portopulmonary hypertension: A case report and literature review. World J Clin Cases 2019; 7:3569-3574. [PMID: 31750339 PMCID: PMC6854406 DOI: 10.12998/wjcc.v7.i21.3569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 09/01/2019] [Accepted: 09/11/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Portopulmonary hypertension (PoPH) is not uncommon in patients waiting for liver transplantation (LT). Severe PoPH has a very high perioperative mortality rate and is still considered a contraindication for LT. Many patients with liver disease require but cannot receive LT due to severe PoPH and eventually died. We report a patient with severe PoPH who underwent successful LT and had near normal pulmonary pressure without drug treatment.
CASE SUMMARY A 39-year-old woman was hospitalized with the chief complaint of jaundice and exertional dyspnea and fatigue. Caroli disease and liver cirrhosis was diagnosed 6 years previously. Her liver disease met the criteria for LT. However, right heart catheterization showed that her mean pulmonary artery pressure was increased at 50 mmHg, pulmonary vascular resistance was 460 dyn∙s/cm5 and pulmonary artery wedge pressure was 20 mmHg, which may have been the reasons for her chief complaint. The patient was diagnosed with severe PoPH and was not listed for LT immediately. After 5 mo of pharmacotherapy, her severe PoPH was moderate, and she underwent successful LT. Pulmonary artery pressure steadily decreased according to post-operative echocardiographic monitoring and drugs have been discontinued for a month.
CONCLUSION The safety of LT can be greatly improved by reducing mean pulmonary artery pressure to a low level, and LT may cure PoPH.
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Affiliation(s)
- Xiao-Jie Chen
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhi-Jun Zhu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 100050, China
- Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing 100050, China
| | - Li-Ying Sun
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
- Clinical Center for Pediatric Liver Transplantation, Capital Medical University, Beijing 100050, China
- Beijing Key Laboratory of Tolerance Induction and Organ Protection in Transplantation, Beijing 100050, China
- Department of Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Lin Wei
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Zhi-Gui Zeng
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Ying Liu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Wei Qu
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Liang Zhang
- Liver Transplantation Center, National Clinical Research Center for Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
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20
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Chen XJ, Zhu ZJ, Sun LY, Wei L, Zeng ZG, Liu Y, Qu W, Zhang L. Liver transplantation for severe portopulmonary hypertension: A case report and literature review. World J Clin Cases 2019. [DOI: 10.12998/wjcc.v7.i21.3552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
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21
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Abstract
The most common pulmonary complications of chronic liver disease are hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension. Hepatic hydrothorax is a transudative pleural effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary disease. Hepatic hydrothorax develops owing to the movement of ascitic fluid into the pleural space. Hepatopulmonary syndrome and portopulmonary hypertension are pathologically linked by the presence of portal hypertension; however, their pathophysiologic mechanisms are significantly different. Hepatopulmonary syndrome is characterized by low pulmonary vascular resistance secondary to intrapulmonary vascular dilatations and hypoxemia; portopulmonary hypertension features elevated pulmonary vascular resistance and constriction/obstruction within the pulmonary vasculature.
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Affiliation(s)
- Rodrigo Cartin-Ceba
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, 200 1st Street SW, Rochester, MN 55905, USA
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22
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Serrano RM, Subbarao GC, Mangus RS, Montgomery G, Johansen M. Combination therapy for severe portopulmonary hypertension in a child allows for liver transplantation. Pediatr Transplant 2019; 23:e13461. [PMID: 31062925 DOI: 10.1111/petr.13461] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 03/12/2019] [Accepted: 04/09/2019] [Indexed: 12/14/2022]
Abstract
Severe PPHTN is a contraindication to liver transplantation and predicts an abysmal 5-year outcome. It is defined as a resting mPAP >45 mm Hg with a mean pulmonary artery wedge pressure of <15 mm Hg and pulmonary vascular resistance of >3 wood units in the setting of portal hypertension. There have been limited reports of successful treatment of PPHTN leading to successful liver transplantation in adults, and one reported use of monotherapy as a bridge to successful liver transplant in pediatrics. To our knowledge, we describe the first use of combination therapy as a successful bridge to liver transplantation in a pediatric patient with severe PPHTN. This report adds to the paucity of data in pediatrics on the use of pulmonary vasodilator therapy in patients with severe PPHTN as a bridge to successful liver transplantation. Early diagnosis in order to mitigate or avoid the development of irreversible pulmonary vasculopathy that would preclude candidacy for liver transplantation is crucial, but our report demonstrates that combination therapy can be administered safely, quickly, and may allow for successful liver transplantation in patients with severe PPHTN.
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Affiliation(s)
- Ryan M Serrano
- Department of Pediatrics, Division of Pediatric Cardiology, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana
| | - Girish C Subbarao
- Department of Pediatrics, Division of Gastroenterology, Hepatology, and Nutrition, University of Indiana School of Medicine and Riley Children's Hospital, Indianapolis, Indiana
| | - Richard S Mangus
- Department of Surgery, Transplant Division, Indiana University School of Medicine, Indianapolis, Indiana
| | - Greg Montgomery
- Section of Pediatric Pulmonology, Critical Care and Allergy, PICU/Riley Hospital for Children, Indianapolis, Indiana
| | - Michael Johansen
- Department of Pediatrics, Division of Pediatric Cardiology, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana
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23
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DesJardin JT, Manicardi M, Svetlichnaya Y, Kolaitis NA, Papolos AI, Selby VN, Zier LS, Klein L, Aras MA, Yao FY, Roberts JP, De Marco T. Noninvasive estimation of pulmonary vascular resistance improves portopulmonary hypertension screening in liver transplant candidates. Clin Transplant 2019; 33:e13585. [DOI: 10.1111/ctr.13585] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Revised: 04/22/2019] [Accepted: 05/04/2019] [Indexed: 01/28/2023]
Affiliation(s)
| | - Marcella Manicardi
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
- Division of Cardiology University of Modena and Reggio Emilia Modena Italy
| | - Yana Svetlichnaya
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
- Division of Cardiology Kaiser Permanente San Francisco California
| | - Nicholas A. Kolaitis
- Department of Medicine University of California San Francisco San Francisco California
- Division of Pulmonology University of California San Francisco San Francisco California
| | - Alexander I. Papolos
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
| | - Van N. Selby
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
| | - Lucas S. Zier
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
- Division of Cardiology Zuckerberg San Francisco General Hospital and Trauma Center San Francisco California
| | - Liviu Klein
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
| | - Mandar A. Aras
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
| | - Francis Y. Yao
- Department of Medicine University of California San Francisco San Francisco California
- Division of Hepatology University of California San Francisco San Francisco California
| | - John P. Roberts
- Division of Transplant Surgery University of California San Francisco San Francisco California
| | - Teresa De Marco
- Department of Medicine University of California San Francisco San Francisco California
- Division of Cardiology University of California San Francisco San Francisco California
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24
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Does Portopulmonary Hypertension Impede Liver Transplantation in Cirrhotic Patients? A French Multicentric Retrospective Study. Transplantation 2018; 102:616-622. [PMID: 29077657 DOI: 10.1097/tp.0000000000001981] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension associated with portal hypertension. Its presence is a major stake for cirrhotic patients requiring liver transplantation (LT), with increased postoperative mortality and unpredictable evolution after transplantation. The aim was to study outcomes after liver transplantation in patients with portopulmonary hypertension and to identify factors associated with normalization of pulmonary hypertension. METHODS Patients with portopulmonary hypertension who underwent LT between 2008 and 2016 in 8 French centers were retrospectively included. Pulmonary artery pressure was established by right heart catheterization before and after LT. Primary endpoint was the normalization of pulmonary artery pressure after LT. RESULTS Twenty-three patients who received liver transplant between 2008 and 2016 were included. Two (8.7%) patients died in the immediate posttransplant period from right heart failure. With appropriate vasoactive medical treatment and LT, pulmonary arterial pressure was normalized in 14 patients (60.8%), demonstrating recovery from portopulmonary hypertension. In univariate analysis, the use of vasoactive combination therapy was the only prognostic factor for pulmonary arterial hypertension normalization after LT. CONCLUSIONS Treatment of portopulmonary hypertension with a combination of vasoactive drugs allows LT with acceptable postoperative cardiovascular-related mortality and normalization of pulmonary hypertension in the majority of the patients.
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25
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Prevalence and Prognosis of Portopulmonary Hypertension in 223 Liver Transplant Recipients. Can Respir J 2018; 2018:9629570. [PMID: 30319722 PMCID: PMC6167565 DOI: 10.1155/2018/9629570] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 05/03/2018] [Accepted: 05/13/2018] [Indexed: 12/23/2022] Open
Abstract
Objective To investigate the prevalence and prognosis of portopulmonary hypertension (PoPH) in liver transplant recipients. Methods Patients with advanced liver disease who underwent orthotopic liver transplantation (OLT) were included in this retrospective study from January 2012 to June 2015. According to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis of pulmonary hypertension (PH), patients with tricuspid regurgitation velocity (TRV) >3.4 m/s or 2.9 m/s ≤ TRV ≤ 3.4 m/s coexisting with other echocardiographic PH signs were judged as PH. PH patients with portal hypertension and without other known causes of PH were diagnosed as PoPH. Results A total of 223 (170 males and 53 females) middle-aged (50.9 ± 9 years old) liver transplant recipients were included in this study. Fourteen patients (6.3%) were diagnosed with PoPH, and none of the patients were treated with vasodilators before or after OLT. After OLT, patients were followed up for 26 ± 13.5 months. In total, 8 of 14 (57%) PoPH patients died, and the main cause of death was pulmonary infection. Kaplan–Meier survival curves revealed a significant difference in survival between PoPH and non-PoPH patients (p < 0.001), and the median survival time after OLT of PoPH was 11.4 months. Conclusions The prevalence of PoPH was 6.3% in OLT recipients. The survival of untreated PoPH patients was dismal after OLT.
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Angeli P, Bernardi M, Villanueva C, Francoz C, Mookerjee RP, Trebicka J, Krag A, Laleman W, Gines P. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol 2018; 69:406-460. [PMID: 29653741 DOI: 10.1016/j.jhep.2018.03.024] [Citation(s) in RCA: 1759] [Impact Index Per Article: 251.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 03/28/2018] [Indexed: 02/06/2023]
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Outcome of Portopulmonary Hypertension After Liver Transplantation: Perhaps Not So Optimistic. Transplantation 2018; 102:e190-e191. [PMID: 29401123 DOI: 10.1097/tp.0000000000002112] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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28
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Koulava A, Sannani A, Levine A, Gupta CA, Khanal S, Frishman W, Bodin R, Wolf DC, Aronow WS, Lanier GM. Diagnosis, Treatment, and Management of Orthotopic Liver Transplant Candidates With Portopulmonary Hypertension. Cardiol Rev 2018; 26:169-176. [PMID: 29608499 DOI: 10.1097/crd.0000000000000195] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable. Any significant right ventricular dysfunction or dilatation along with an elevation in estimated pulmonary pressures usually triggers further investigation with right heart catheterization. The mainstays of therapy of POPH are vasodilators that are used in pulmonary arterial hypertension. They include monotherapy or combination therapy with prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors/guanylate cyclase stimulator. Limited evidence from smaller studies and case series suggests that a timely diagnosis of POPH and the early initiation of treatment improve patient outcomes, whether or not OLT is ultimately undertaken. Given the historically high perioperative mortality rate of more than 35%, POPH remains a contraindication to OLT unless it is treated and responsive to vasodilator therapy. We review the current literature and International Liver Transplant Society practice guidelines (2016) for the latest in understanding POPH, its pathogenesis, diagnosis, modern pharmacological treatment, indications, and contraindications for OLT, as well as perioperative management.
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Affiliation(s)
| | | | | | | | | | | | - Roxana Bodin
- Division of Transplant Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
| | - David C Wolf
- Division of Transplant Hepatology, New York Medical College/Westchester Medical Center, Valhalla, NY
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Herborn J, Parulkar S. Anesthetic Considerations in Transplant Recipients for Nontransplant Surgery. Anesthesiol Clin 2017; 35:539-553. [PMID: 28784225 DOI: 10.1016/j.anclin.2017.04.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
As solid organ transplantation increases and patient survival improves, it will become more common for these patients to present for nontransplant surgery. Recipients may present with medical problems unique to the transplant, and important considerations are necessary to keep the transplanted organ functioning. A comprehensive preoperative examination with specific focus on graft functioning is required, and the anesthesiologist needs pay close attention to considerations of immunosuppressive regimens, blood product administration, and the risk benefits of invasive monitoring in these immunosuppressed patients. This article reviews the posttransplant physiology and anesthetic considerations for patients after solid organ transplantation.
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Affiliation(s)
- Joshua Herborn
- Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
| | - Suraj Parulkar
- Department of Anesthesiology, Northwestern University Feinberg School of Medicine, 251 East Huron Street, F5-704, Chicago, IL 60611, USA
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30
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International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation 2017; 100:1440-52. [PMID: 27326810 DOI: 10.1097/tp.0000000000001229] [Citation(s) in RCA: 286] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.
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Savale L, Sattler C, Coilly A, Conti F, Renard S, Francoz C, Bouvaist H, Feray C, Borentain P, Jaïs X, Montani D, Parent F, O'Connell C, Hervé P, Humbert M, Simonneau G, Samuel D, Calmus Y, Duvoux C, Durand F, Duclos-Vallée JC, Sitbon O. Long-term outcome in liver transplantation candidates with portopulmonary hypertension. Hepatology 2017; 65:1683-1692. [PMID: 27997987 DOI: 10.1002/hep.28990] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2016] [Revised: 11/06/2016] [Accepted: 11/26/2016] [Indexed: 02/04/2023]
Abstract
UNLABELLED Portopulmonary hypertension (PoPH) is diagnosed in 2-6% of liver transplantation (LT) candidates. We studied outcomes of candidates for LT suffering from PoPH. Data were collected retrospectively from a prospective registry. Pulmonary hemodynamic variables were collected at the time of PoPH diagnosis, at last evaluation before LT, and within 6 months and beyond 6 months after LT. Forty-nine patients (35 males, 48 ± 8 years) were analyzed (median Model for End-Stage Liver Disease score 20). At baseline, mean pulmonary artery pressure (mPAP) was 44 ± 10 mm Hg (range 26-73 mm Hg), cardiac index was 3.5 ± 0.9 L/min/m2 , and pulmonary vascular resistance was 5.6 ± 2.8 Wood units. Hemodynamic reassessment performed in 35 patients who were treated with pulmonary arterial hypertension-targeted therapies before LT resulted in significant decreases in both mPAP (36 ± 7 versus 47 ± 10 mm Hg, P < 0.0001) and pulmonary vascular resistance (3.0 ± 1.4 versus 6.1 ± 3.1 Wood units, P < 0.0001). Fourteen patients (29%) died without having had access to LT. Thirty-five patients underwent LT and were followed up for a median of 38 months. Eight patients (23%) died after LT including 5 due to PoPH (after 1 day to 6 months). Among survivors (n = 27), all patients treated with intravenous epoprostenol were weaned off post-LT, and endothelin receptor antagonist or phosphodiesterase type 5 inhibitors were continued in 15/27 patients (55%). At last evaluation, 20/27 patients (74%) had mPAP <35 mm Hg and 8 of them (30%) had mPAP <25 mm Hg. Overall survival estimates after LT were 80%, 77%, and 77% at 6 months, 1 year, and 3 years, respectively. CONCLUSION Stabilization or reversibility of PoPH seems to be an attainable goal using the combination of pulmonary arterial hypertension-targeted therapies and LT in patients who are transplantation candidates. (Hepatology 2017;65:1683-1692).
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Affiliation(s)
- Laurent Savale
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Caroline Sattler
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Audrey Coilly
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, F-94800, France
| | - Filoména Conti
- Service de Transplantation Hépatique, APHP, Hôpital Pitié Salpêtrière, Paris, France
| | - Sébastien Renard
- Département de Cardiologie, Hôpital La Timone, Aix-Marseille Université, Marseille, France
| | - Claire Francoz
- Service de Transplantation Hépatique, APHP, Hôpital Beaujon, Paris, France
| | | | - Cyrille Feray
- Service de Transplantation Hépatique, APHP, Hôpital Henri Mondor, Paris, France
| | - Patrick Borentain
- Service d'hépatogastroenterologie, Hôpital La Timone, Aix-Marseille Université, Marseille, France
| | - Xavier Jaïs
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - David Montani
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Florence Parent
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Caroline O'Connell
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Philippe Hervé
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Marc Humbert
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Gérald Simonneau
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
| | - Didier Samuel
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, F-94800, France
| | - Yvon Calmus
- Service de Transplantation Hépatique, APHP, Hôpital Pitié Salpêtrière, Paris, France
| | - Christophe Duvoux
- Service de Transplantation Hépatique, APHP, Hôpital Henri Mondor, Paris, France
| | - François Durand
- Service de Transplantation Hépatique, APHP, Hôpital Beaujon, Paris, France
| | - Jean Charles Duclos-Vallée
- AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 1193, Université Paris-Saclay, Villejuif, F-94800, France; Inserm, Unité 1193, Université Paris-Saclay, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, F-94800, France
| | - Olivier Sitbon
- Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, and AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre; INSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
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Kulik TJ, Austin ED. Pulmonary hypertension's variegated landscape: a snapshot. Pulm Circ 2017; 7:67-81. [PMID: 28680566 PMCID: PMC5448531 DOI: 10.1177/2045893216686930] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Accepted: 11/29/2016] [Indexed: 01/29/2023] Open
Abstract
The many types of pulmonary hypertension (PH) are so protean in their biological origin, histological expression, and natural history that it is difficult to create a summary picture of the disease, or to easily compare and contrast characteristics of one type of PH with another. For newcomers to the field, however, such a picture would facilitate a broad understanding of PH. In this paper, we suggest that four characteristics are fundamental to describing the nature of various types of PH, and that taken together they define a number of patterns of PH expression. These characteristics are histopathology, developmental origin, associated clinical conditions, and potential for resolution. The “snapshot” is a way to concisely display the ways that these signal characteristics intersect in select specific types of PH, and is an effort to summarize these patterns in a way that facilitates a “big picture” comprehension of this disease.
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Affiliation(s)
- Thomas J Kulik
- Department of Cardiology, Division of Cardiac Critical Care, and the Pulmonary Hypertension Program, Boston Children's Hospital, Boston, MA, USA
| | - Eric D Austin
- Vanderbilt Pediatric Pulmonary Hypertension Program, Vanderbilt Medical Center North, Nashville, TN, USA
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Abstract
Portopulmonary hypertension (POPH) is a form of pulmonary arterial hypertension occurring in the setting of portal hypertension with or without hepatic cirrhosis. The presence of both portal and pulmonary vascular disease contributes to complicated hemodynamics and therapeutic challenges, though the severities do not appear to correlate directly. Diagnosis of POPH, and distinction from the commonly observed hyperdynamic state of end-stage liver disease, is typically accomplished with an initial screening transthoracic echocardiogram, followed by right heart catheterization for confirmation of hemodynamic parameters. Though few studies have directly evaluated use in POPH, pulmonary artery-directed therapy is the cornerstone of management, along with consideration of liver transplantation. Perioperative and long-term outcomes are variable, but uniformly worse in the setting of uncontrolled pulmonary pressures. Risk stratification and optimal patient selection for these interventions are areas of ongoing investigation.
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Rodríguez-Almendros N, Toapanta-Yanchapaxi LN, Aguirre Valadez J, Espinola Zavaleta N, Muñoz-Martínez SG, García-Juárez I. [Portopulmonary hypertension: Updated review]. ARCHIVOS DE CARDIOLOGIA DE MEXICO 2016; 88:25-38. [PMID: 27986561 DOI: 10.1016/j.acmx.2016.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 11/08/2016] [Accepted: 11/08/2016] [Indexed: 11/19/2022] Open
Abstract
Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain.
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Affiliation(s)
- Nielzer Rodríguez-Almendros
- Departamento de Hipertensión Pulmonar y Función Ventricular Derecha, UMAE Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, D.F., México
| | - Liz N Toapanta-Yanchapaxi
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Jonathan Aguirre Valadez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Nilda Espinola Zavaleta
- Departamento de Ecocardiografia, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México
| | - Sergio G Muñoz-Martínez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Ignacio García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
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35
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Savaş Bozbaş Ş, Eroğlu S, Öner Eyüboğlu F, Moray G, Haberal M. Pulmonary Hypertension Improves After Orthotopic Liver Transplant in Patients With Chronic Liver Disease. EXP CLIN TRANSPLANT 2016; 13 Suppl 3:115-9. [PMID: 26640929 DOI: 10.6002/ect.tdtd2015.p65] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Pulmonary hypertension is a common finding in chronic liver disease patients that has prognostic significance. In this study, we aimed to evaluate the prevalence and severity of pulmonary hypertension in patients undergoing orthotopic liver transplant. We also evaluated pulmonary artery pressure changes after transplant surgery. MATERIALS AND METHODS The records of adult patients with chronic liver disease who underwent orthotopic liver transplant at our center between 2004 and 2015 were retrospectively evaluated. Clinical and demographic variables and laboratory data were noted. Transthoracic Doppler echocardiographic examination reports were obtained. Using continuous-wave Doppler examination, systolic pulmonary artery pressure values were calculated. Pulmonary hypertension was defined as systolic pulmonary artery pressure ≥ 30 mm Hg. Among 208 adult patients who underwent orthotopic liver transplant, 203 who had Doppler echocardiographic examination were enrolled. RESULTS The mean age of patients was 42.1 ± 14.1 years (range, 16-67 y), and 143 (70.4%) were men. During preoperative assessment, pulmonary hypertension was identified in 47 patients (23.2%), of whom 10 displayed systolic pulmonary artery pressure > 50 mm Hg. Compared with preoperative values of systolic pulmonary artery pressure (46.8 ± 8.4 mm Hg), a significant reduction in mean values (to 39.3 ± 13.3 mm Hg) was observed postoperatively (P = .007). CONCLUSIONS The findings of this study indicate that pulmonary hypertension is a common finding in adult chronic liver disease patients undergoing orthotopic liver transplant. A significant improvement occurs in systolic pulmonary artery pressure values following transplant surgery. Regarding the prevalence and prognostic significance of pulmonary hypertension, all patients with chronic liver disease should be evaluated with transthoracic Doppler echocardiography before transplant.
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Affiliation(s)
- Şerife Savaş Bozbaş
- From the Department of Pulmonary Diseases, Başkent University Faculty of Medicine, Ankara, Turkey
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36
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Abstract
Portopulmonary hypertension (PoPH) refers to the condition that pulmonary arterial hypertension (PAH) occur in the stetting of portal hypertension. The development of PoPH is thought to be independent of the severity of portal hypertension or the etiology or severity of liver disease. PoPH results from excessive vasoconstriction, vascular remodeling, and proliferative and thrombotic events within the pulmonary circulation that lead to progressive right ventricular failure and ultimately to death. Untreated PoPH is associated with a poor prognosis. As PoPH is frequently asymptomatic or symptoms are generally non-specific, patients should be actively screened for the presence of PoPH. Two-dimensional transthoracic echocardiography is a useful non-invasive screening tool, but a definitive diagnosis requires invasive hemodynamic confirmation by right heart catheterization. Despite a dearth of randomized, prospective data, an ever-expanding clinical experience shows that patients with PoPH benefit from therapy with PAH-specific medications including with endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and/or prostanoids. Due to high perioperative mortality, transplantation should be avoided in those patients who have severe PoPH that is refractory to medical therapy.
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Affiliation(s)
- Yong Lv
- a Department of Liver Diseases and Digestive Interventional Radiology , Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an , China
| | - Guohong Han
- a Department of Liver Diseases and Digestive Interventional Radiology , Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an , China
| | - Daiming Fan
- b State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases , Fourth Military Medical University , Xi'an , China
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Schussler JM, Asrani SK, Ramsay MAE, Trotter JF. Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral IV. Liver Transpl 2016; 22:695-7. [PMID: 26953818 DOI: 10.1002/lt.24432] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2016] [Revised: 02/07/2016] [Accepted: 02/18/2016] [Indexed: 01/13/2023]
Affiliation(s)
- Jeffrey M Schussler
- Department of Internal Medicine, Baylor University Medical Center, Dallas, TX.,Division of Cardiology, Texas A&M University, College Station, TX.,Jack and Jane Hamilton Heart and Vascular Hospital, Texas A&M University, College Station, TX.,College of Medicine, Texas A&M University, College Station, TX
| | - Sumeet K Asrani
- Department of Internal Medicine, Baylor University Medical Center, Dallas, TX.,Division of Cardiology, Texas A&M University, College Station, TX
| | - Michael A E Ramsay
- Department of Internal Medicine, Baylor University Medical Center, Dallas, TX.,Division of Anesthesiology, Texas A&M University, College Station, TX
| | - James F Trotter
- Department of Internal Medicine, Baylor University Medical Center, Dallas, TX.,Division of Transplant Hepatology, Texas A&M University, College Station, TX
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38
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Bozbas SS, Bozbas H. Portopulmonary hypertension in liver transplant candidates. World J Gastroenterol 2016; 22:2024-2029. [PMID: 26877607 PMCID: PMC4726675 DOI: 10.3748/wjg.v22.i6.2024] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 10/21/2015] [Accepted: 12/21/2015] [Indexed: 02/06/2023] Open
Abstract
Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed.
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Goldberg DS, Fallon MB. The Art and Science of Diagnosing and Treating Lung and Heart Disease Secondary to Liver Disease. Clin Gastroenterol Hepatol 2015; 13:2118-27. [PMID: 25934564 PMCID: PMC4618073 DOI: 10.1016/j.cgh.2015.04.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Revised: 04/13/2015] [Accepted: 04/14/2015] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are at risk of extrahepatic complications related to cirrhosis and portal hypertension, as well as organ-specific complications of certain liver diseases. These complications can compromise quality of life, while also increasing morbidity and mortality before and after liver transplantation. Patients with chronic liver disease are at risk for pulmonary complications of hepatopulmonary syndrome and portopulmonary syndrome; the cardiac complication fall under the general concept of cirrhotic cardiomyopathy, which can affect systolic and diastolic function, as well as cardiac conduction. In addition, patients with certain diseases are at risk of lung and/or cardiac complications that are specific to the primary disease (ie, emphysema in α-1-antitrypsin deficiency) or occur with increased incidence in certain conditions (ie, ischemic heart disease associated with nonalcoholic steatohepatitis). This article focuses on the epidemiology, clinical presentation, pathogenesis, treatment options, and role of transplantation for lung and heart diseases secondary to liver disease, while also highlighting select liver diseases that directly affect the lungs and heart.
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Affiliation(s)
- David S Goldberg
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Michael B Fallon
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
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Abstract
OBJECTIVE Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature. METHODS Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients. RESULTS In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively. CONCLUSIONS POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk.
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DuBrock HM, Channick RN, Krowka MJ. What's new in the treatment of portopulmonary hypertension? Expert Rev Gastroenterol Hepatol 2015; 9:983-92. [PMID: 25882070 DOI: 10.1586/17474124.2015.1035647] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Portopulmonary hypertension (POPH) is a complication of portal hypertension characterized by pulmonary vasoconstriction and vascular remodeling that can lead to right heart failure and death. Differentiation of POPH from other causes of pulmonary hypertension, such as volume overload or a hyperdynamic high flow state, is critical because a diagnosis of POPH has significant implications for liver transplant risk stratification, Model for End Stage Liver Disease exception points, and the use of pulmonary arterial hypertension-(PAH) specific therapy. Currently, there are 12 approved medications for the treatment of PAH in the US, and three of these were approved in 2013. This review will discuss the diagnosis, evaluation and management of POPH and the role of recently approved PAH therapies in the treatment of POPH.
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Affiliation(s)
- Hilary M DuBrock
- Massachusetts General Hospital, 55 Fruit St Boston MA 02114, USA
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MacKenzie AM, Peacock AJ. Medical Therapies for the Treatment of Pulmonary Arterial Hypertension: How Do We Choose? Curr Hypertens Rep 2015; 17:56. [DOI: 10.1007/s11906-015-0560-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Meng FY, Liu L, Yang FH, Li CY, Liu J, Zhou P. Reversible immortalization of human hepatocytes mediated by retroviral transfer and site-specific recombination. World J Gastroenterol 2014; 20:13119-13126. [PMID: 25278705 PMCID: PMC4177490 DOI: 10.3748/wjg.v20.i36.13119] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2014] [Revised: 03/30/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish a method for the reversible immortalization of human hepatocytes, which may offer a good and safe source of hepatocytes for practical applications.
METHODS: We successfully isolated primary human hepatocytes from surgically resected liver tissue taken from a patient with liver hemangiomas. The freshly isolated cells were then immortalized with retroviral vector SSR#69 expressing simian virus 40 large T antigen (SV40T) and hygromycin-resistance genes flanked by paired loxP recombination targets.
RESULTS: The freshly isolated hepatocytes with high viability (85%) were successfully immortalized using retroviral gene transfer of SV40T. SV40T in the immortalized cells was then excised by Cre/loxP site-specific recombination. This cell population exhibited the characteristics of differentiated hepatocytes.
CONCLUSION: We successfully established reversibly immortalized human hepatocytes, which will provide an unlimited supply of cells for practical applications.
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Krowka MJ, Cartin-Ceba R. Portopulmonary hypertension: formidable dual threat versus hopeful dual therapy. Liver Transpl 2014; 20:635-6. [PMID: 24711442 DOI: 10.1002/lt.23885] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2014] [Accepted: 03/31/2014] [Indexed: 01/28/2023]
Affiliation(s)
- Michael J Krowka
- William J. von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, MN
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