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Zaka AZ, Mangoura SA, Ahmed MA. New updates on hepatopulmonary syndrome: A comprehensive review. Respir Med 2025; 236:107911. [PMID: 39662637 DOI: 10.1016/j.rmed.2024.107911] [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: 09/12/2024] [Revised: 11/28/2024] [Accepted: 12/08/2024] [Indexed: 12/13/2024]
Abstract
Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes arterial hypoxemia in the setting of liver disease. HPS has a progressive course and is associated with a two-fold increased risk of mortality relative to cirrhotic patients without HPS. It primarily affects patients with portal hypertension. The key pathological features of HPS include intrapulmonary angiogenesis and vascular dilations (IPVDs). The prevalence of HPS varies widely due to inconsistent diagnostic criteria and a lack of standardized protocols. Despite advances in understanding its pathophysiology, no effective curative treatments for HPS exist. Liver transplantation remains the only definitive treatment, improving survival and altering the disease natural course. This review explores the pathophysiology, clinical features, and therapeutic strategies for HPS, highlighting recent advances in the literature.
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Affiliation(s)
- Andrew Z Zaka
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
| | - Safwat A Mangoura
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo, 11829, Egypt.
| | - Marwa A Ahmed
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt
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Halliday N, Burns SO, Lowe DM, Thorburn D. Reply: Hepatopulmonary syndrome associated with common variable immunodeficiency: Is it reasonable to investigate? Hepatol Commun 2024; 8:e0538. [PMID: 39495138 PMCID: PMC11537556 DOI: 10.1097/hc9.0000000000000538] [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: 06/26/2024] [Accepted: 06/26/2024] [Indexed: 11/05/2024] Open
Affiliation(s)
- Neil Halliday
- UCL Institute for Liver and Digestive Health, University College London, London, UK
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | - Siobhan O. Burns
- Institute of Immunity and Transplantation, University College London, London, UK
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK
| | - David M. Lowe
- Institute of Immunity and Transplantation, University College London, London, UK
- Department of Immunology, Royal Free London NHS Foundation Trust, London, UK
| | - Douglas Thorburn
- UCL Institute for Liver and Digestive Health, University College London, London, UK
- Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
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Verstraeten M, Lefere S, Raevens S. Pulmonary vascular complications of cirrhosis: hepatopulmonary syndrome and portopulmonary hypertension. Acta Clin Belg 2024; 79:384-391. [PMID: 39873530 DOI: 10.1080/17843286.2025.2456697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Accepted: 01/13/2025] [Indexed: 01/30/2025]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two distinct pulmonary vascular complications seen in patients with liver disease and/or portal hypertension. HPS is characterized by disturbed gas exchange and hypoxemia because of intrapulmonary vascular dilatations. POPH is defined by pulmonary arterial hypertension, which might lead to right heart failure. HPS affects up to 30% of patients with end-stage liver disease requiring liver transplantation. POPH is rarer and affects 1-5% of this patient population. If not recognized and left untreated, these disorders result in significant mortality. This review provides an update on HPS and POPH and discusses their clinical characteristics, screening and diagnostic modalities, and management, including the place of liver transplantation.
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Affiliation(s)
- Maïté Verstraeten
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Ghent, Belgium
| | - Sander Lefere
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Ghent, Belgium
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
- Hepatology Research Unit, Department of Internal Medicine and Pediatrics, Liver Research Center, Ghent University, Ghent, Belgium
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Alberto LD, Fagundes EDT, Rodrigues AT, Queiroz TCN, Castro GVD, Ferreira AR. HEPATOPULMONARY SYNDROME IN PEDIATRIC PATIENTS WITH PORTAL HYPERTENSION - AN INTEGRATIVE REVIEW. ARQUIVOS DE GASTROENTEROLOGIA 2024; 61:e24040. [PMID: 39230090 DOI: 10.1590/s0004-2803.24612024-040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 05/23/2024] [Indexed: 09/05/2024]
Abstract
BACKGROUND Hepatopulmonary syndrome (HPS) is characterized by the triad of abnormal arterial oxygenation caused by intrapulmonary vascular dilatations (IPVD) in the setting of advanced liver disease or portal hypertension, impacting the patient's quality of life and survival. There are still many gaps in the literature on this topic, especially in pediatrics, with practices frequently based on extrapolation of data obtained from adults. OBJECTIVE Provide a synthesis of the current knowledge about HPS in children. METHODS The research was carried out through narrative review. The databases used for the search include Medline, Embase, Elsevier, Lilacs and Scielo. The keywords used were "hepatopulmonary syndrome" AND child, children, infant, preschool, pediatric. RESULTS In cirrhotic children, the prevalence of HPS can reach up to 42.5%, and it is even more common in those whose underlying condition is biliary atresia, reaching up to 63%. Screening with pulse oximetry (O2 saturation <96%), unlike in adults, has low sensitivity in the pediatric age group. Management involves supportive care with oxygen therapy; liver transplantation is the only definitive treatment to reverse the condition and HPS is considered an exceptional criterion for waitlist. The waitlist mortality is similar among children listed by HPS as a special criterion when compared to those listed for other reasons. The reported rates of complete resolution of hypo-xemia after liver transplantation are close to 100% in children. The post-liver transplantation survival is similar or slightly lower in children with HPS when compared to those without HPS. Contrary to findings from adults, no differences were found in post- liver transplantation mortality between children of different hypoxemia ranges, although longer mechanical ventilation time and hospital stay were observed in children with PaO2 <50 mmHg. CONCLUSION HPS is not an uncommon complication of cirrhosis in children and adolescents, particularly when biliary atresia is the underlying condition. There are still many gaps to be filled regarding the condition, and this article demonstrates that not all data obtained in studies with adults reflects the disease's behavior in pediatrics, especially concerning prognosis.
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Affiliation(s)
- Letícia Drumond Alberto
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Grupo de Gastroenterologia Pediátrica, Belo Horizonte, MG, Brasil
| | - Eleonora Druve Tavares Fagundes
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Grupo de Gastroenterologia Pediátrica, Belo Horizonte, MG, Brasil
- Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Adriana Teixeira Rodrigues
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Grupo de Gastroenterologia Pediátrica, Belo Horizonte, MG, Brasil
- Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
| | - Thaís Costa Nascentes Queiroz
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Grupo de Gastroenterologia Pediátrica, Belo Horizonte, MG, Brasil
| | | | - Alexandre Rodrigues Ferreira
- Hospital das Clínicas da Universidade Federal de Minas Gerais, Grupo de Gastroenterologia Pediátrica, Belo Horizonte, MG, Brasil
- Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brasil
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Mauz JB, Rieland H, Berliner D, Tiede A, Stockhoff L, Hinrichs JB, Wedemeyer H, Meyer BC, Olsson KM, Maasoumy B, Tergast TL. High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation. Clin Gastroenterol Hepatol 2024; 22:1867-1877.e4. [PMID: 38729401 DOI: 10.1016/j.cgh.2024.04.027] [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: 11/16/2023] [Revised: 04/06/2024] [Accepted: 04/11/2024] [Indexed: 05/12/2024]
Abstract
BACKGROUND & AIMS Considerate patient selection is vital to ensure the best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVDs) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD), and liver transplant (LTx)-free survival within 1 year of follow-up. RESULTS Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine, and more often received TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (hazard ratio [HR], 1.756; 95% confidence interval [CI], 1.011-3.048; P = .046) and HD (HR, 1.841; 95% CI, 1.255-2.701; P = .002). However, LTx-free survival was comparable between patients with and without IPVD (HR, 1.081; 95% CI, 0.630-1.855; P = .780). Patients with HPS displayed a trend towards more CD (HR, 1.708; 95% CI, 0.935-3.122; P = .082) and HD (HR, 1.458; 95% CI, 0.934-2.275; P = .097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared with patients without HPS, respectively (HR, 1.052; 95% CI, 0.577-1.921; P = .870). CONCLUSION Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of CD and HD.
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Affiliation(s)
- Jim B Mauz
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany
| | - Hannah Rieland
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany
| | - Dominik Berliner
- Hannover Medical School, Department of Cardiology and Angiology, Hannover, Germany
| | - Anja Tiede
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany
| | - Lena Stockhoff
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany
| | - Jan B Hinrichs
- St Bernward Hospital, Department of Radiology, Hildesheim, Germany
| | - Heiner Wedemeyer
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany; Excellence Cluster Resist, Hannover Medical School, Hannover, Germany
| | - Bernhard C Meyer
- Hannover Medical School, Department of Diagnostic and Interventional Radiology, Hannover, Germany
| | - Karen M Olsson
- Hannover Medical School, Department of Respiratory Medicine and Infectious Diseases, Hannover, Germany; German Center for Lung Research (DZL), Hannover, Germany
| | - Benjamin Maasoumy
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany; German Center for Infection Research (DZIF), Hannover-Braunschweig, Germany.
| | - Tammo L Tergast
- Hannover Medical School, Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover, Germany.
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. [Not Available]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Müller M, Grasshoff C. [The Role of the Anaesthesiologist in Liver Transplantation - Preoperative Evaluation]. Anasthesiol Intensivmed Notfallmed Schmerzther 2024; 59:283-295. [PMID: 38759684 DOI: 10.1055/a-2152-7350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/19/2024]
Abstract
Preoperative evaluation prior to listing for orthotopic liver transplantation (LT) requires a careful multidisciplinary approach with specialized teams including surgeons, hepatologists and anesthesiologists in order to improve short- and long-term clinical outcomes. Due to inadequate supply of donor organs and changing demographics, patients listed for LT have become older, sicker and share more comorbidities. As cardiovascular events are the leading cause for early mortality precise evaluation of risk factors is mandatory. This review focuses on the detection and management of coronary artery disease, cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome in patients awaiting LT. Further insights are being given into scoring systems, patients with Acute-on-chronic-liver-failure (ACLF), frailty, NASH cirrhosis and into psychologic evaluation of patients with substance abuse.
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Zhao X, Kotha S, Nayyar D, Ma X, Lilly L, Castel H, Gupta S. Physiologic changes in the hepatopulmonary syndrome before and after liver transplant: A longitudinal and predictor analysis. Hepatology 2024; 79:636-649. [PMID: 37732952 PMCID: PMC10871618 DOI: 10.1097/hep.0000000000000605] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Accepted: 08/27/2023] [Indexed: 09/22/2023]
Abstract
BACKGROUND AND AIMS Hepatopulmonary syndrome (HPS) is a common complication of liver disease defined by abnormal oxygenation and intrapulmonary vascular dilatation, treated with liver transplantation. Little is known about changes in HPS physiological parameters over time. We sought to describe baseline clinical and physiological characteristics in HPS and their relationships, temporal changes in physiological parameters before and after transplant, and predictors of changes in oxygenation. APPROACH AND RESULTS This was a retrospective cohort study in the Canadian HPS Program (n = 132). Rates of change after diagnosis were: -3.7 (-6.4, -0.96) mm Hg/year for partial pressure of arterial oxygen (PaO 2 ); -26 (-96, 44) m/year for 6-minute walk distance, and 3.3% (-6.6, -0.011) predicted/year for diffusion capacity. Noninvasive shunt of ≥ 20% predicted a slower PaO 2 decline by 0.88 (0.36, 1.4) mm Hg/month. We identified 2 PaO 2 deterioration classes-"very severe disease, slow decliners" (PaO 2 45.0 mm Hg; -1.0 mm Hg/year); and "moderate disease, steady decliners" (PaO 2 65.5 mm Hg; -2.5 mm Hg/year). PaO 2 increased by 6.5 (5.3, 7.7) mm Hg/month in the first year after transplant. The median time to normalization was 149 (116, 184) days. Posttransplant improvement in PaO 2 was 2.5 (0.1, 4.9) mm Hg/month faster for every 10 mm Hg greater pretransplant orthodeoxia. CONCLUSIONS We present a large and long longitudinal data analysis in HPS. In addition to rates of physiological decline and improvement before and after liver transplantation, we present novel predictors of PaO 2 decline and improvement rates. Our findings enhance our understanding of the natural history of HPS and provide pathophysiologic clues. Importantly, they may assist providers in prognostication and prioritization before and after transplant.
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Affiliation(s)
- Xun Zhao
- Department of Gastroenterology and Hepatology, McGill University, Montreal, Canada
- Department of Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Sreelakshmi Kotha
- Department of Hepatology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK
| | - Dhruv Nayyar
- Department of Medicine, University of Toronto, Toronto, Canada
| | - Xiayi Ma
- Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, Canada
| | - Leslie Lilly
- Department of Multi-Organ Transplant, Toronto General Hospital, University of Toronto, Toronto, Canada
| | - Hélène Castel
- Department of Hepatology and Liver Transplantation, Centre Hospitalier de l’Université de Montréal (CHUM), Montreal, Canada
| | - Samir Gupta
- Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, University of Toronto, Toronto, Canada
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Sayadi A, Duhaut L, Robert F, Savale L, Coilly A. [Hepatopulmonary syndrome]. Rev Med Interne 2024; 45:156-165. [PMID: 37005097 DOI: 10.1016/j.revmed.2023.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 03/07/2023] [Accepted: 03/17/2023] [Indexed: 04/03/2023]
Abstract
The hepatopulmonary syndrome (HPS) is one of the lung diseases associated with cirrhosis and portal hypertension. It should be discussed for any dyspnea in cirrhotic patients. HPS is a pulmonary vascular disease characterized by intrapulmonary vascular dilatations (IPVD). The pathogenesis is complex and seems to rely on communications between the portal and pulmonary circulations. The diagnosis is based on a triad of liver disease and portal hypertension, evidence of IPVDs, and impaired gas exchange (alveolar-arterial oxygen difference [A-aO2]≥15mmHg). HPS impairs prognosis (23% survival at 5years) and patients' quality of life. Liver transplantation (LT) allows regression of IPDVD in almost 100% of cases, normalization of gas exchange and improves survival with a 5-year post-LT survival between 76 and 87%. It is the only curative treatment, indicated in patients with severe HPS, defined by an arterial partial pressure of oxygen (PaO2) below 60mmHg. When LT is not indicated or feasible, long-term oxygen therapy may be proposed as a palliative treatment. A better understanding of the pathophysiological mechanisms is needed to improve the therapeutic possibilities in a near future.
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Affiliation(s)
- A Sayadi
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France
| | - L Duhaut
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France
| | - F Robert
- Inserm UMR_S 999, 94270 Le Kremlin-Bicêtre, France
| | - L Savale
- Inserm UMR_S 999, 94270 Le Kremlin-Bicêtre, France; Service de pneumologie, hôpital Bicêtre, université Paris-Saclay, AP-HP, 94270 Le Kremlin-Bicêtre, France
| | - A Coilly
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France.
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10
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Chooklin S, Chuklin S. Hepatopulmonary syndrome: diagnosis and treatment. EMERGENCY MEDICINE 2024; 19:511-518. [DOI: 10.22141/2224-0586.19.8.2023.1640] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Hepatopulmonary syndrome (HPS) is one of the lung diseases associated with liver cirrhosis and portal hypertension. The diagnosis is based on the triad: liver disease and portal hypertension, evidence of intrapulmonary vascular dilatation and impaired gas exchange. HPS impairs prognosis (23 % survival after 5 years) and patients’ quality of life, so early diagnosis and timely treatment are of great importance. Liver transplantation allows for regression of intrapulmonary vascular dilatation in almost 100 % of cases, normalization of gas exchange and improves a 5-year survival after transplantation from 76 to 87 %. This is the only treatment method indicated for patients with severe HPS, defined by an arterial partial pressure of oxygen (PaO2) below 60 mm Hg. However, in the face of a global shortage of transplants, it is necessary to develop medical therapies to delay or even defer liver transplantation. This goal seems possible due to the growing understanding of the HPS pathophysiology and the development of therapies targeting key mechanisms, mainly inflammatory and angiogenic. This article provides an overview of the clinical manifestations, diagnosis and treatment of HPS based on literature sources from the MEDLINE database on the PubMed platform.
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Koc ÖM, Aslan D, Kramer M, Verbeek J, Van Malenstein H, van der Merwe S, Monbaliu D, Vos R, Verleden GM, Pirenne J, Nevens F. Outcomes of liver transplantation for hepatopulmonary syndrome in patients with concomitant respiratory disease. Clin Transplant 2024; 38:e15171. [PMID: 37897208 DOI: 10.1111/ctr.15171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 09/05/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND & AIMS Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease. METHODS This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020. RESULTS During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463). CONCLUSIONS The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy.
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Affiliation(s)
- Özgür M Koc
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Devrim Aslan
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Matthijs Kramer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jef Verbeek
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Hannah Van Malenstein
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Schalk van der Merwe
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Robin Vos
- Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium
| | - Geert M Verleden
- Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
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12
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Han SK, Baik SK, Kim MY. [Pulmonary Complications in Patients with Liver Cirrhosis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 82:213-223. [PMID: 37997217 DOI: 10.4166/kjg.2023.123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/01/2023] [Accepted: 11/02/2023] [Indexed: 11/25/2023]
Abstract
Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Korea
- Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Korea
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13
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Fiala A, Breitkopf R, Sinner B, Mathis S, Martini J. [Anesthesia for organ transplant patients]. DIE ANAESTHESIOLOGIE 2023; 72:773-783. [PMID: 37874343 PMCID: PMC10615924 DOI: 10.1007/s00101-023-01332-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/27/2023] [Indexed: 10/25/2023]
Abstract
Organ transplant patients who must undergo nontransplant surgical interventions can be challenging for the anesthesiologists in charge. On the one hand, it is important to carefully monitor the graft function in the perioperative period with respect to the occurrence of a possible rejection reaction. On the other hand, the ongoing immunosuppression may have to be adapted to the perioperative requirements in terms of the active substance and the route of administration, the resulting increased risk of infection and possible side effects (e.g., myelosuppression, nephrotoxicity and impairment of wound healing) must be included in the perioperative treatment concept. Furthermore, possible persistent comorbidities of the underlying disease and physiological peculiarities as a result of the organ transplantation must be taken into account. Support can be obtained from the expertise of the respective transplantation center.
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Affiliation(s)
- Anna Fiala
- Universitätsklinik für Anästhesie und Intensivmedizin, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich
| | - Robert Breitkopf
- Universitätsklinik für Anästhesie und Intensivmedizin, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich.
| | - Barbara Sinner
- Universitätsklinik für Anästhesie und Intensivmedizin, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich
| | - Simon Mathis
- Universitätsklinik für Anästhesie und Intensivmedizin, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich
| | - Judith Martini
- Universitätsklinik für Anästhesie und Intensivmedizin, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich
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14
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Panackel C, Fawaz M, Jacob M, Raja K. Pulmonary Assessment of the Liver Transplant Recipient. J Clin Exp Hepatol 2023; 13:895-911. [PMID: 37693254 PMCID: PMC10483013 DOI: 10.1016/j.jceh.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 04/13/2023] [Indexed: 09/12/2023] Open
Abstract
Respiratory symptoms and hypoxemia can complicate chronic liver disease and portal hypertension. Various pulmonary disorders affecting the pleura, lung parenchyma, and pulmonary vasculature are seen in end-stage liver disease, complicating liver transplantation (LT). Approximately 8% of cirrhotic patients in an intensive care unit develop severe pulmonary problems. These disorders affect waiting list mortality and posttransplant outcomes. A thorough history, physical examination, and appropriate laboratory tests help diagnose and assess the severity to risk stratify pulmonary diseases before LT. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH) are respiratory consequences specific to cirrhosis and portal hypertension. HPS is seen in 5-30% of cirrhosis cases and is characterized by impaired oxygenation due to intrapulmonary vascular dilatations and arteriovenous shunts. Severe HPS is an indication of LT. The majority of patients with HPS resolve their hypoxemia after LT. When pulmonary arterial hypertension occurs in patients with portal hypertension, it is called POPH. All other causes of pulmonary arterial hypertension should be ruled out before labeling as POPH. Since severe POPH (mean pulmonary artery pressure [mPAP] >50 mm Hg) is a relative contraindication for LT, it is crucial to screen for POPH before LT. Those with moderate POPH (mPAP >35 mm Hg), who improve with medical therapy, will benefit from LT. A transudative pleural effusion called hepatic hydrothorax (HH) is seen in 5-10% of people with cirrhosis. Refractory cases of HH benefit from LT. In recent years, increasing clinical expertise and advances in the medical field have resulted in better outcomes in patients with moderate to severe pulmonary disorders, who undergo LT.
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Affiliation(s)
| | - Mohammed Fawaz
- Integrated Liver Care, Aster Medcity, Kochi, Kerala, India
| | - Mathew Jacob
- Integrated Liver Care, Aster Medcity, Kochi, Kerala, India
| | - Kaiser Raja
- King's College Hospital London, Dubai Hills, Dubai, United Arab Emirates
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15
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Brankovic M, Lee P, Pyrsopoulos N, Klapholz M. Cardiac Syndromes in Liver Disease: A Clinical Conundrum. J Clin Transl Hepatol 2023; 11:975-986. [PMID: 37408802 PMCID: PMC10318294 DOI: 10.14218/jcth.2022.00294] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 09/28/2022] [Accepted: 11/28/2022] [Indexed: 07/03/2023] Open
Abstract
Understanding the interaction between the heart and liver is pivotal for managing patients in whom both organs are affected. Studies have shown that cardio-hepatic interactions are bidirectional and that their identification, assessment, and treatment remain challenging. Congestive hepatopathy is a condition that develops in the setting of long-standing systemic venous congestion. If left untreated, congestive hepatopathy may lead to hepatic fibrosis. Acute cardiogenic liver injury develops as a combination of venous stasis and sudden arterial hypoperfusion due to cardiac, circulatory, or pulmonary failure. The treatment of both conditions should be directed toward optimizing the cardiac substrate. Hyperdynamic syndrome may develop in patients with advanced liver disease and lead to multiorgan failure. Cirrhotic cardiomyopathy or abnormalities in pulmonary vasculature, such as hepatopulmonary syndrome and portopulmonary hypertension may also develop. Each complication has unique treatment challenges and implications for liver transplantation. The presence of atrial fibrillation and atherosclerosis in liver disease brings another layer of complexity, particularly in terms of anticoagulation and statin use. This article provides an overview of cardiac syndromes in liver disease, focusing on current treatment options and future perspectives.
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Affiliation(s)
- Milos Brankovic
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
- Transatlantic Cardiovascular Study Group, Bloomfield, NJ, USA
| | - Paul Lee
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Nikolaos Pyrsopoulos
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Mark Klapholz
- Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ, USA
- Division of Cardiology, Heart Failure Prevention and Treatment Program, Rutgers New Jersey Medical School, Newark, NJ, USA
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16
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Tanaka H. Advances in pediatric liver transplantation from the pediatric surgeon's perspective. Pediatr Surg Int 2023; 39:253. [PMID: 37624479 DOI: 10.1007/s00383-023-05533-8] [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] [Accepted: 08/06/2023] [Indexed: 08/26/2023]
Abstract
Pediatric liver transplantation is a lifesaving state-of-the-art operation for children with various liver diseases, including cholestatic diseases, metabolic disorders, acute liver failure, and primary malignant liver tumors. Among these indications, transplantation for biliary atresia and hepatoblastoma is discussed in this review because pediatric surgeons are usually involved in their initial treatments. For biliary atresia, pediatric surgeons are advised to keep dissection of the hilar structures to a minimum during Kasai portoenterostomy in order to make total hepatectomy easier at transplantation. Early referral to a transplant team is recommended when worrisome signs of liver dysfunction, cirrhosis, portal hypertension and growth retardation are noted. Hepatoblastoma with multiplicity or located close to major vessels may indicate unresectability, and the transplant team needs to be consulted early after neoadjuvant chemotherapy is started. The graft size, including its thickness, needs to be evaluated before transplantation for small children, as tailoring the shape of the partial graft may be necessary during the transplant procedure.
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Affiliation(s)
- Hideaki Tanaka
- Department of Pediatric Surgery, and Department of Transplantation Medicine, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, Fukushima, 960-1295, Japan.
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17
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Chan SKT, Lim ZMJ, Tay SM. Navigating a complicated liver transplant in a patient with severe hepatopulmonary syndrome without extracorporeal membrane oxygenation: a case report. Singapore Med J 2023; 64:538-542. [PMID: 35082107 PMCID: PMC10476917 DOI: 10.11622/smedj.2022002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 09/28/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Steffi Kang Ting Chan
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
| | | | - Sook Muay Tay
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
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18
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Furuta Y, Sugahara M, Nakamura T, Tominaga K, Kijima Y. Platypnea-Orthodeoxia: An Effective Diagnostic Tool for Hepatopulmonary Syndrome With Chronic Obstructive Pulmonary Disease. Cureus 2023; 15:e35904. [PMID: 37033506 PMCID: PMC10081502 DOI: 10.7759/cureus.35904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2023] [Indexed: 04/11/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) shows progressive dyspnea resulting from intrapulmonary atrioventricular shunts in liver cirrhosis. The comorbidity of chronic lung disease often hampers the diagnosis of progressive dyspnea in patients with HPS. Therefore, a comprehensive approach to the determination of dyspnea is required. Here, this case report shows that a patient with chronic obstructive pulmonary disease (COPD) and alcoholic liver cirrhosis was diagnosed with HPS after admission due to worsening dyspnea. Although COPD exacerbation was initially suspected because of the long history of smoking, physical examinations, laboratory findings, and imaging data, dyspnea remained after recovery from worsening respiratory failure. HPS was suspected due to the absence of increased CO2 levels and the presence of platypnea-orthodeoxia. We diagnosed the intrapulmonary arteriovenous shunt with microbubble-contrast echocardiography and technetium-99m macroaggregated albumin scintigraphy. Therefore, this case highlighted that HPS rather than COPD was suspected of hypoxemia associated with repositioning for the differential diagnosis of dyspnea.
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Affiliation(s)
- Yuzo Furuta
- Department of Cardiology, Japan Community Healthcare Organization Hoshigaoka Medical Center, Osaka, JPN
| | - Masataka Sugahara
- Department of Cardiology, Japan Community Healthcare Organization Hoshigaoka Medical Center, Osaka, JPN
| | - Takahito Nakamura
- Department of General Internal Medicine, Nara Prefecture Seiwa Medical Center, Nara, JPN
| | - Kazunari Tominaga
- Department of Gastroenterology, Japan Community Healthcare Organization Hoshigaoka Medical Center, Osaka, JPN
| | - Yoshiyuki Kijima
- Department of Cardiology, Japan Community Healthcare Organization Hoshigaoka Medical Center, Osaka, JPN
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19
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Raza MH, Kwon Y, Kobierski P, Misra AC, Lim A, Goldbeck C, Etesami K, Kohli R, Emamaullee J. Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation. Liver Transpl 2023; 29:134-144. [PMID: 37160070 PMCID: PMC9868062 DOI: 10.1002/lt.26548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/11/2022] [Accepted: 07/14/2022] [Indexed: 01/29/2023]
Abstract
Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.
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Affiliation(s)
- Muhammad H Raza
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Yong Kwon
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Pierre Kobierski
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Asish C Misra
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Angelina Lim
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Cameron Goldbeck
- Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA
| | - Kambiz Etesami
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Rohit Kohli
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA.,Department of Pediatrics , University of Southern California , Los Angeles , California , USA
| | - Juliet Emamaullee
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
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20
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Wray CL, Chadha R. Cardiopulmonary considerations for the anesthetic management of liver transplantation. CARDIO-HEPATOLOGY 2023:293-307. [DOI: 10.1016/b978-0-12-817394-7.00014-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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21
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Douschan P, Kovacs G, Sassmann T, Stadlbauer V, Avian A, Foris V, Tatscher E, Durchschein F, Rainer F, Spindelboeck W, Wagner M, Kniepeiss D, Zollner G, Bachmaier G, Fickert P, Olschewski H, Stauber RE. Pulmonary vascular disease and exercise hemodynamics in chronic liver disease. Respir Med 2022; 202:106987. [PMID: 36115317 DOI: 10.1016/j.rmed.2022.106987] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 08/27/2022] [Accepted: 09/06/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND & AIMS Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are severe pulmonary vascular complications of chronic liver disease and strongly associated with morbidity and mortality. The prevalence of these complications is relatively high in patients evaluated for liver transplantation, however it is virtually unknown in patients with stable chronic liver disease. METHODS We assessed the pulmonary hypertension (PH) and HPS prevalence in a prospective registry study of our liver out-patient clinic in a tertiary center. Between 2011 and 2016, consecutive patients with cirrhosis or non-cirrhotic portal hypertension were prospectively enrolled after written informed consent. We excluded patients with acute decompensation of liver disease and other causes of PH like severe chronic heart or lung diseases and chronic thromboembolic PH. HPS was diagnosed using contrast enhanced echocardiography and blood gas analysis. Patients were screened for PH using an algorithm implementing severity of dyspnea, echocardiography, cardiopulmonary exercise testing and exercise echocardiography employing a threshold of systolic pulmonary arterial pressure (SPAP) = 50 mmHg at peak exercise. If the algorithm indicated an increased PH risk, patients were invited for invasive investigations by means of right heart and hepatic vein catheter. We defined POPH as resting mPAP≥21 mmHg and PVR>3WU and PAWP<15 mmHg, mild PH as resting mPAP = 21-24 mmHg, and exercise PH as mPAP>30 mmHg and TPR >3 WU at peak exercise. RESULTS Two-hundred-five patients were enrolled (male 75%; cirrhosis 96%; median age 57 yrs). Sixty-seven patients (33%) fulfilled HPS criteria but only two (1.0%) for severe (PaO2:50-60 mmHg) or very severe HPS (PaO2<50 mmHg). In 18/77 patients (23%) undergoing exercise echocardiography, SPAP at peak exercise exceeded 50 mmHg. Finally, n = 3 (1.5%) patients were invasively diagnosed with POPH, n = 4 (2.9%) with mild PH and n = 2 with exercise PH. CONCLUSION In chronic liver disease, excluding acute decompensation and other causes of PH, POPH and severe HPS are rare findings while mild to moderate HPS and mild PH or exercise PH are more frequent.
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Affiliation(s)
- Philipp Douschan
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Gabor Kovacs
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria.
| | - Teresa Sassmann
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Vanessa Stadlbauer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Alexander Avian
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Vasile Foris
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Elisabeth Tatscher
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Franziska Durchschein
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Walter Spindelboeck
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Martin Wagner
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Daniela Kniepeiss
- Department of General, Visceral and Transplant Surgery, Transplant Center Graz, Medical University of Graz, Graz, Austria
| | - Gernot Zollner
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Gerhard Bachmaier
- Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria
| | - Peter Fickert
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Horst Olschewski
- Department of Internal Medicine, Division of Pulmonology, Medical University of Graz, Graz, Austria; Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria
| | - Rudolf E Stauber
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
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22
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Zhao H, Tsauo J, Zhang X, Ma H, Weng N, Yang Z, Li X. Prevalence and prognostic impact of hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study. Chin Med J (Engl) 2022; 135:2043-2048. [PMID: 36255217 PMCID: PMC9746741 DOI: 10.1097/cm9.0000000000002034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). METHODS Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study. RESULTS Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9-16.3) months for patients with HPS and 15.1 (95% CI, 7.3-22.9) months for patients without HPS, which is not a significant difference ( P = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0-12.8] vs. 8.4 [95% CI, 3.6-13.1] months; P = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003-1.064]; P = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011-3.260]; P = 0.046) were identified to be the independent prognostic factors of OS. CONCLUSION Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.
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Affiliation(s)
- He Zhao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jiaywei Tsauo
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Xiaowu Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Huaiyuan Ma
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Ningna Weng
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
| | - Zhengqiang Yang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China
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Zafar M, Patel A, Ashraf M, Tibble J. Shortness of breath due to portopulmonary hypertension and hepatopulmonary syndrome: diagnostic challenges and complex management approach in frail patients. Clin Med (Lond) 2022; 22:485-489. [PMID: 38589073 PMCID: PMC9595008 DOI: 10.7861/clinmed.2022-0293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
A 60-year-old woman with a background of frailty, non-alcoholic fatty liver disease (NAFLD), cirrhosis and type 2 diabetes mellitus (T2DM), presented with worsening shortness of breath and a drop in oxygen saturation on sitting and standing up. Her chest X-ray demonstrated evidence of upper lobe venous diversion. Given the hypoxia, she had a computed tomography pulmonary angiography (CTPA) to rule out a pulmonary embolism. The only finding from the CTPA was pulmonary hypertension in the absence of any clots in the lungs. An ultrasound of the abdomen confirmed portal hypertension with splenomegaly and a cirrhotic liver, therefore, an initial diagnosis of portopulmonary hypertension and hepatopulmonary syndrome was made. The patient declined an agitated saline contrast echocardiography. Based on frailty she was not deemed to be a suitable candidate for a liver transplant and was discharged with a package of care alongside home oxygen therapy with periodic review in the gastroenterology clinic. She was assessed as stable with no new concerns while on home oxygen and diuretics. This case highlights challenges in diagnosing and managing patients with cirrhosis, portopulmonary hypertension and hepatopulmonary syndrome with a background of complex comorbidities and frailty.
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Kawut SM, Krowka MJ, Forde KA, Al-Naamani N, Krok KL, Patel M, Bartoli CR, Doyle M, Moutchia J, Lin G, Oh JK, Mottram CD, Scanlon PD, Fallon MB. Impact of hepatopulmonary syndrome in liver transplantation candidates and the role of angiogenesis. Eur Respir J 2022; 60:2102304. [PMID: 34949701 PMCID: PMC10967655 DOI: 10.1183/13993003.02304-2021] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2021] [Accepted: 11/30/2021] [Indexed: 11/05/2022]
Abstract
BACKGROUND Hepatopulmonary syndrome affects 10-30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation. METHODS The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease. RESULTS We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12-19) versus 14 (10-17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03-3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02-3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome. CONCLUSION Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.
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Affiliation(s)
- Steven M Kawut
- Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Center for Clinical Epidemiology and Biostatistics, Dept of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | | | - Kimberly A Forde
- Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Center for Clinical Epidemiology and Biostatistics, Dept of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Nadine Al-Naamani
- Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Karen L Krok
- Dept of Medicine, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Mamta Patel
- Dept of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Center for Clinical Epidemiology and Biostatistics, Dept of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Carlo R Bartoli
- Division of Cardiovascular Surgery, Dept of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
- Division of Cardiothoracic Surgery, Dept of Medicine, Geisinger Medical Center, Danville, PA, USA
| | - Margaret Doyle
- Dept of Pathology, University of Vermont, Burlington, VT, USA
| | - Jude Moutchia
- Center for Clinical Epidemiology and Biostatistics, Dept of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Grace Lin
- Dept of Medicine, Mayo Clinic, Rochester, MN, USA
| | - Jae K Oh
- Dept of Medicine, Mayo Clinic, Rochester, MN, USA
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Saner FH, Hoyer DP, Hartmann M, Nowak KM, Bezinover D. The Edge of Unknown: Postoperative Critical Care in Liver Transplantation. J Clin Med 2022; 11:jcm11144036. [PMID: 35887797 PMCID: PMC9322367 DOI: 10.3390/jcm11144036] [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: 06/10/2022] [Revised: 06/29/2022] [Accepted: 07/07/2022] [Indexed: 02/04/2023] Open
Abstract
Perioperative care of patients undergoing liver transplantation (LT) is very complex. Metabolic derangements, hypothermia, coagulopathy and thromboses, severe infections, and graft dysfunction can affect outcomes. In this manuscript, we discuss several perioperative problems that can be encountered in LT recipients. The authors present the most up-to-date information regarding predicting and treating hemodynamic instability, coagulation monitoring and management, postoperative ventilation strategies and early extubation, management of infections, and ESLD-related pulmonary complications. In addition, early post-transplant allograft dysfunction will be discussed.
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Affiliation(s)
- Fuat H. Saner
- Department of General-, Visceral- and Transplant Surgery, Medical Center University Duisburg-Essen, 45147 Essen, Germany; (D.P.H.); (K.M.N.)
- Correspondence: ; Fax: +49-201-723-1145
| | - Dieter P. Hoyer
- Department of General-, Visceral- and Transplant Surgery, Medical Center University Duisburg-Essen, 45147 Essen, Germany; (D.P.H.); (K.M.N.)
| | - Matthias Hartmann
- Department of Anaesthesia and Critical Care, Medical Center University Duisburg-Essen, 45147 Essen, Germany;
| | - Knut M. Nowak
- Department of General-, Visceral- and Transplant Surgery, Medical Center University Duisburg-Essen, 45147 Essen, Germany; (D.P.H.); (K.M.N.)
| | - Dmitri Bezinover
- Department of Anesthesiology and Perioperative Medicine, Penn State Hershey Medical Center, Penn State College of Medicine, Hershey, PA 17033, USA;
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Raevens S, Boret M, Fallon MB. Hepatopulmonary syndrome. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2022; 4:100527. [PMID: 36035361 PMCID: PMC9403489 DOI: 10.1016/j.jhepr.2022.100527] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/10/2022] [Accepted: 06/15/2022] [Indexed: 11/25/2022]
Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease, which adversely affects prognosis. The disease is characterised by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange. A complex interaction between the liver, the gut and the lungs, predominately impacting pulmonary endothelial cells, immune cells and respiratory epithelial cells, is responsible for the development of typical pulmonary alterations seen in HPS. Liver transplantation is the only therapeutic option and generally reverses HPS. Since the implementation of the model for end-stage liver disease (MELD) standard exception policy, outcomes in patients with HPS have been significantly better than they were in the pre-MELD era. This review summarises current knowledge and highlights what’s new regarding the diagnosis and management of HPS, and our understanding of pathogenesis based on experimental models and translational studies.
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27
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Craciun R, Mocan T, Procopet B, Nemes A, Tefas C, Sparchez M, Mocan LP, Sparchez Z. Pulmonary complications of portal hypertension: The overlooked decompensation. World J Clin Cases 2022; 10:5531-5540. [PMID: 35979136 PMCID: PMC9258359 DOI: 10.12998/wjcc.v10.i17.5531] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/22/2022] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
The systemic nature of cirrhosis and portal hypertension has long been recognized, and the amount of data characterizing the interplay between each system is becoming ever so complex. Lung involvement was among the first described associated entities in cirrhosis, with reports dating back to the late nineteenth century. However, it appears that throughout the years, interest in the pulmonary complications of portal hypertension has generally faded, especially in contrast to other decompensating events, as expertise in this field has primarily been concentrated in highly experienced tertiary care facilities and liver transplantation centers. Despite affecting up to 10%-15% of patients with advanced liver disease and having a proven prognostic impact, hepato-pulmonary syndrome, porto-pulmonary hypertension, and hepatic hydrothorax are frequently misdiagnosed, mistreated, or misinterpreted. This lack of precision might adversely impact patient care, referral to expert centers, and, ultimately, liver disease-related mortality and successful transplantation odds. The present minireview aims to increase awareness of the pulmonary complications of chronic liver disease by providing a brief overview of each of the three entities. The paper focuses on the essential theoretical aspects, addressing the most critical knowledge gaps on the one hand and, on the other hand, critically discussing one key issue for each complication.
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Affiliation(s)
- Rares Craciun
- 3rd Medical Clinic, Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
- Gastroenterology Clinic, "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
| | - Tudor Mocan
- 3rd Medical Clinic, Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
- Gastroenterology Clinic, "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
| | - Bogdan Procopet
- 3rd Medical Clinic, Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
- Gastroenterology Clinic, "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
| | - Andrada Nemes
- Intensiv Care Unit I, Cluj County Emergency Hosptial, Cluj-Napoca 400006, Romania
| | - Cristian Tefas
- 3rd Medical Clinic, Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
- Gastroenterology Clinic, "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
| | - Mihaela Sparchez
- 2nd Paediatric Clinic, ”Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca 400126, Please enter the state or province, Romania
| | - Lavinia-Patricia Mocan
- Department of Histology, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400349, Romania
| | - Zeno Sparchez
- 3rd Medical Clinic, Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca 400162, Romania
- Gastroenterology Clinic, "Prof. Dr. O. Fodor" Regional Institute of Gastroenterology and Hepatology, Cluj-Napoca 400162, Romania
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28
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Wu WK, Grogan WM, Ziogas IA, Patel YJ, Bacchetta M, Alexopoulos SP. Extracorporeal membrane oxygenation in patients with hepatopulmonary syndrome undergoing liver transplantation: A systematic review of the literature. Transplant Rev (Orlando) 2022; 36:100693. [DOI: 10.1016/j.trre.2022.100693] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/31/2022] [Accepted: 04/03/2022] [Indexed: 02/07/2023]
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Huang J, Yoeli D, Sundaram SS, Carpenter T, Annam A, Pahlavan S, Wachs M, Adams MA. Extracorporeal membrane oxygenation as rescue therapy in a pediatric liver transplant recipient with very severe hepatopulmonary syndrome. Pediatr Transplant 2022; 26:e14185. [PMID: 34741368 DOI: 10.1111/petr.14185] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Accepted: 10/22/2021] [Indexed: 11/28/2022]
Abstract
BACKGROUND In children with cirrhosis, the prevalence of HPS ranges from 3% to 20%, resulting in impaired gas exchange due to alterations in pulmonary microvasculature. LT is the gold-standard cure for cirrhosis complicated by HPS and should ideally be performed prior to the development of severe HPS due to increased risk for post-transplant hypoxia, right heart failure, and outflow obstruction. METHODS We present a case of a 13-year-old man, who underwent pediatric LT for severe HPS complicated by postoperative respiratory collapse, requiring a 92-day course of veno-venous ECMO. RESULTS Post-transplant, despite BiPAP, inhaled nitric oxide and isoproterenol infusion, he remained hypoxic postoperatively and acutely decompensated on postoperative day 25, requiring veno-venous ECMO. After 84 days on ECMO, a persistent large splenorenal shunt was identified that was embolized by interventional radiology, and 8 days after shunt embolization and ASD closure, he was successfully weaned off ECMO. CONCLUSIONS This case describes the longest known duration of ECMO in a pediatric LT recipient and a unique improvement in hypoxemia following a portosystemic shunt closure. ECMO presents a heroic rescue measure for pediatric LT recipients with HPS that develops acute respiratory failure postoperatively refractory to alternative measures.
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Affiliation(s)
- Joy Huang
- University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Dor Yoeli
- Division of Transplant Surgery, Colorado Center for Transplantation Care, Research and Education, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA
| | - Shikha S Sundaram
- Section of Gastroenterology, Hepatology, and Nutrition, Digestive Health Institute, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA
| | - Todd Carpenter
- Department of Pediatrics, Section of Pediatric Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA
| | - Aparna Annam
- Division of Pediatric Radiology, Department of Radiology, University of Colorado and Children's Hospital Colorado, Aurora, Colorado, USA
| | - Sheila Pahlavan
- University of Colorado School of Medicine, Aurora, Colorado, USA
| | - Michael Wachs
- Colorado Center for Transplantation Care, Research and Education, Division of Transplant Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA
| | - Megan A Adams
- Colorado Center for Transplantation Care, Research and Education, Division of Transplant Surgery, University of Colorado Denver School of Medicine and Children's Hospital Colorado, Aurora, Colorado, USA
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30
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Certain MC, Robert F, Baron A, Sitbon O, Humbert M, Guignabert C, Tu L, Savale L. Syndrome hépatopulmonaire : prévalence, physiopathologie et implications cliniques. Rev Mal Respir 2022; 39:84-89. [DOI: 10.1016/j.rmr.2022.02.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 01/05/2022] [Indexed: 11/28/2022]
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31
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Iwasaki S, Ueno T, Toyama C, Deguchi K, Nomura M, Saka R, Watanabe M, Tazuke Y, Bessho K, Okuyama H. A Retransplant Case for Hepatopulmonary Syndrome Without Liver Cirrhosis or Portosystemic Shunt After Living-Donor Liver Transplantation: A Case Report. Transplant Proc 2022; 54:552-555. [PMID: 35074161 DOI: 10.1016/j.transproceed.2021.12.022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Accepted: 12/29/2021] [Indexed: 10/19/2022]
Abstract
Hepatopulmonary syndrome (HPS) is a disease of gas exchange caused by intrapulmonary shunting secondary to liver disease-associated intrapulmonary vascular dilation. HPS is characterized by the triad of cirrhosis, chronic liver disease, or portosystemic shunting (PSS); arterial hypoxemia; and intrapulmonary arteriovenous shunting in the absence of a primary cardiopulmonary anomaly. We encountered a rare case of HPS without liver disease or PSS. The patient was an 8-year-old girl who underwent living donor liver transplantation (LDLT) shortly after developing fulminant hepatitis at 11 months of her age. Eight years after LDLT, hypoxemia and shortness of breath developed. The shunt ratio on 99mTc-macroaggregated albumin (MAA) lung perfusion scintigraphy (99mTc-MAA lung scan) was 32%. The patient had no cardiopulmonary disease, so we diagnosed her illness as HPS. We did not find cirrhosis, chronic liver disease, or PSS as a cause of HPS. We thought the graft was the cause of HPS. A second transplantation was planned. One year after the diagnosis of HPS, the shunt ratio on 99mTc-MAA lung scan worsened to 42%, digital clubbing appeared, and hypoxemia was worsening. Thus, we performed a second LDLT. After LDLT the shunt ratio on 99mTc-MAA lung scan normalized (6%) and cyanosis resolved. We determined that the graft was the cause of HPS; the typical causes of HPS were not clearly revealed in the histologic examination of the second liver explant. Acute rejection occurred twice after LDLT, so we speculated that HPS occurred because the graft became stressed over the long term.
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Affiliation(s)
- Shun Iwasaki
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Takehisa Ueno
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
| | - Chiyoshi Toyama
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Koichi Deguchi
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Motonari Nomura
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Ryuta Saka
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Miho Watanabe
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Yuko Tazuke
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Kazuhiko Bessho
- Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
| | - Hiroomi Okuyama
- Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
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Gandhi KD, Taweesedt PT, Sharma M, Surani S. Hepatopulmonary syndrome: An update. World J Hepatol 2021; 13:1699-1706. [PMID: 34904039 PMCID: PMC8637683 DOI: 10.4254/wjh.v13.i11.1699] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 06/25/2021] [Accepted: 08/31/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is characterized by defects in oxygenation caused by intra-pulmonary vasodilation occurring because of chronic liver disease, portal hypertension, or congenital portosystemic shunts. Clinical implications of portal hypertension are very well-known, however, awareness of its effect on multiple organs such as the lungs are less known. The presence of HPS in chronic liver disease is associated with increased mortality. Medical therapies available for HPS have not been proven effective and definitive treatment for HPS is mainly liver transplantation (LT). LT improves mortality for patients with HPS drastically. This article provides a review on the definition, clinical presentation, diagnosis, and management of HPS.
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Affiliation(s)
- Kejal D Gandhi
- Department of Internal Medicine, Medstar Washington Hospital Center/Georgetown University, Washigton, DC 20010, United States
| | - Pahnwat Tonya Taweesedt
- Department of Medicine, Corpus Christi Medical Center, Corpus Christi, TX 78412, United States
| | - Munish Sharma
- Department of Medicine, Corpus Christi Medical Center, Corpus Christi, TX 78412, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, Bryan, TX 78413, United States
- Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, United States.
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Chandna S, Zarate ER, Gallegos-Orozco JF. Management of Decompensated Cirrhosis and Associated Syndromes. Surg Clin North Am 2021; 102:117-137. [PMID: 34800381 DOI: 10.1016/j.suc.2021.09.005] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Patients with cirrhosis account for 3% of intensive care unit admissions with hospital mortality exceeding 50%; however, improvements in survival among patients with acutely decompensated cirrhosis and organ failure have been described when treated in specialized liver transplant centers. Acute-on-chronic liver failure is a distinct clinical syndrome characterized by decompensated cirrhosis associated with one or more organ failures resulting in a significantly higher short-term mortality. In this review, we will discuss the management of common life-threatening complications in the patient with cirrhosis that require intensive care management including neurologic, cardiovascular, gastrointestinal, pulmonary, and renal complications.
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Affiliation(s)
- Shaun Chandna
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA
| | - Eduardo Rodríguez Zarate
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA
| | - Juan F Gallegos-Orozco
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Utah School of Medicine, 30 N 1900 E, SOM-4R118, Salt Lake City, UT 84106, USA.
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Bommena S, Gerkin RD, Agarwal S, Raevens S, Glassberg MK, Fallon MB. Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System. Clin Gastroenterol Hepatol 2021; 19:2370-2378. [PMID: 33007510 DOI: 10.1016/j.cgh.2020.09.050] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/26/2020] [Accepted: 09/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system. METHODS A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria. RESULTS A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers. CONCLUSIONS The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms.
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Affiliation(s)
- Shoma Bommena
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center-Phoenix, Phoenix, Arizona.
| | - Richard D Gerkin
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center-Phoenix, Phoenix, Arizona
| | - Sumit Agarwal
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center-Phoenix, Phoenix, Arizona
| | - Sarah Raevens
- Department of Internal Medicine, Ghent University, Ghent, Belgium
| | - Marilyn K Glassberg
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center-Phoenix, Phoenix, Arizona
| | - Michael B Fallon
- Department of Medicine, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona; Department of Internal Medicine, Banner University Medical Center-Phoenix, Phoenix, Arizona
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Del Valle K, DuBrock HM. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Pulmonary Vascular Complications of Liver Disease. Compr Physiol 2021; 11:3281-3302. [PMID: 34636408 DOI: 10.1002/cphy.c210009] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Pulmonary vascular disease is a frequent complication of chronic liver disease and portal hypertension, affecting up to 30% of patients. There are two distinct pulmonary vascular complications of liver disease: hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). HPS affects 25% of patients with chronic liver disease and is characterized by intrapulmonary vasodilatation and abnormal arterial oxygenation. HPS negatively impacts quality of life and is associated with a 2-fold increased risk of death compared to controls with liver disease without HPS. Angiogenesis, endothelin-1 mediated endothelial dysfunction, monocyte influx, and alveolar type 2 cell dysfunction seem to play important roles in disease pathogenesis but there are currently no effective medical therapies. Fortunately, HPS resolves following liver transplant (LT) with improvements in hypoxemia. POPH is a subtype of pulmonary arterial hypertension (PAH) characterized by an elevated mean pulmonary arterial pressure and pulmonary vascular resistance in the setting of normal left-sided filling pressures. POPH affects 5% to 6% of patients with chronic liver disease. Although the pathogenesis has not been fully elucidated, endothelial dysfunction, inflammation, and estrogen signaling have been identified as key pathways involved in disease pathogenesis. POPH is typically treated with PAH targeted therapy and may also improve with liver transplantation in selected patients. This article highlights what is currently known regarding the diagnosis, management, pathobiology, and outcomes of HPS and POPH. Ongoing research is needed to improve understanding of the pathophysiology and outcomes of these distinct and often misunderstood pulmonary vascular complications of liver disease. © 2021 American Physiological Society. Compr Physiol 11:1-22, 2021.
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Parikh H, Lui E, Faughnan ME, Al-Hesayen A, Segovia S, Gupta S. Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial. Trials 2021; 22:683. [PMID: 34625098 PMCID: PMC8500814 DOI: 10.1186/s13063-021-05633-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 09/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia-an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients. METHODS We propose a randomized controlled crossover trial in patients with moderate HPS (PaO2 < 80 mmHg) and orthodeoxia (supine to upright PaO2 decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70-85% of the predicted peak work rate until the "stopping time" is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects. P < 0.05 will be considered statistically significant. DISCUSSION HPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration and Results System (PRS) NCT04004104 . Registered on 1 July 2019.
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Affiliation(s)
- Harsh Parikh
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada
| | - Eric Lui
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada
| | - Marie E Faughnan
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada.,Division of Respirology, St. Michael's Hospital, Toronto, Canada
| | - Abdul Al-Hesayen
- Department of Medicine, University of Toronto, Toronto, Canada.,Division of Cardiology, St Michael's Hospital, Toronto, Canada
| | | | - Samir Gupta
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada. .,Department of Medicine, University of Toronto, Toronto, Canada. .,Division of Respirology, St. Michael's Hospital, Toronto, Canada.
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Kadry Z, Schaefer E, Krok K, Faust A, Stine JG, Schreibman IR, Bezinover D, Riley TR. Excellent outcomes with liver transplantation in hepatopulmonary syndrome across pre-transplant PaO 2 spectrum. JHEP Rep 2021; 3:100351. [PMID: 34604726 PMCID: PMC8473556 DOI: 10.1016/j.jhepr.2021.100351] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2021] [Revised: 08/02/2021] [Accepted: 08/03/2021] [Indexed: 02/07/2023] Open
Abstract
Background & Aims Significantly worse survival has been reported in patients with hepatopulmonary syndrome (HPS) and partial pressure of arterial oxygen (PaO2) <45 mmHg undergoing liver transplantation. Long-term pre- and post-transplant outcomes based on degree of hypoxaemia were re-examined. Methods A retrospective analysis of 1,152 HPS candidates listed with an approved HPS model for end-stage liver disease (MELD) exception was performed. A Fine and Gray competing risks model was utilised to evaluate pre-transplant outcomes for PaO2 thresholds of <45, 45 to <60, and ≥60 mmHg. Post-transplant survival was analysed using the Kaplan-Meier method. Results Patients with a PaO2 <45 mmHg were significantly more likely to undergo transplantation (hazard ratio [HR] 1.51; 95% CI 1.12-2.03), whereas patients with higher MELD scores had lower hazard of transplant (HR 0.80, 95% CI 0.67-0.95, p = 0.011) and higher hazard of pre-transplant death (HR 2.29, 95% CI 1.55-3.37, p <0.001). Post-transplantation, patients with a PaO2 <45 mmHg had lower survival (p = 0.04) compared with patients with a PaO2 ≥45 to <50 mmHg, with survival curves significantly different at 2.6 years (75% survival compared with 86%) and median survival of 11.5 and 14.1 years, respectively. Cardiac arrest was a more likely (p = 0.025) cause of death for these patients. Cardiac arrest incidence in patients who died with a PaO2 >50 mmHg was 6.2%. Conclusions Patients with a PaO2 <45 mmHg had a significantly higher rate of transplantation, and higher calculated MELD scores were associated with significantly higher pre-transplant mortality. Although post-transplant survival was lower in patients with a PaO2 <45 mmHg, the median survival was 11.5 years, and survival curves only became significantly different at 2.6 years. This suggests that patients with HPS do benefit from transplantation up to 2-3 years post-transplant regardless of the severity of pre-transplant hypoxaemia. Lay summary A total of 1,152 patients with hepatopulmonary syndrome listed for liver transplant were analysed. Patients with a low PaO2 <45 mmHg had a high likelihood of transplantation. If associated with advanced liver disease, the mortality risk was higher for patients with hepatopulmonary syndrome on the wait list. After liver transplantation, patients with a PaO2 <45 mmHg had a lower survival, but this only became significant after 2.6 years, and the median survival was 11.5 years. This suggests that patients with hepatopulmonary syndrome do benefit from transplantation.
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Key Words
- CIF, cumulative incidence function
- ECMO, extracorporeal membrane oxygenation
- HPS, hepatopulmonary syndrome
- HR, hazard ratio
- Hepatopulmonary syndrome
- Hypoxia
- Liver transplantation
- MELD, model for end-stage liver disease
- NASH, non-alcoholic steatohepatitis
- OPTN, Organ Procurement and Transplant Network
- POPH, portopulmonary hypertension
- PaO2, partial pressure of arterial oxygen
- STAR, Standard Transplant Analysis and Research
- UNOS, United Network for Organ Sharing
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Affiliation(s)
- Zakiyah Kadry
- Division of Transplantation, Department of Surgery, Penn State College of Medicine, Hershey, PA, USA
| | - Eric Schaefer
- Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA
| | - Karen Krok
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Alison Faust
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Jonathan Gibson Stine
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Ian Roy Schreibman
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
| | - Dmitri Bezinover
- Department of Anesthesiology, Penn State College of Medicine, Hershey, PA, USA
| | - Thomas Roberts Riley
- Division of Gastroenterology and Hepatology, Department of Medicine, Penn State College of Medicine, Hershey, PA, USA
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Miah N, Ryan A, Oztumer CA, Saleh M. First presentation of portal hypertension complicated by hepatopulmonary syndrome. BMJ Case Rep 2021; 14:e244712. [PMID: 34544713 PMCID: PMC8454437 DOI: 10.1136/bcr-2021-244712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/07/2021] [Indexed: 11/04/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is a serious complication of chronic liver disease, characterised by portal hypertension and arterial hypoxaemia due to intrapulmonary vascular dilatation. We report an unusual case in which a 27-year-old man had a first presentation of portal hypertension and cirrhosis complicated by HPS. This patient presented with progressive dyspnoea on exertion and deterioration in mobility, with a type 1 respiratory failure and increased oxygen demand. A bubble echocardiogram showed a possible right-to-left shunt, CT aortogram displayed evidence of portal hypertension and cirrhosis, and liver biopsy findings were consistent with alpha-1 antitrypsin deficiency. The patient's increased oxygen demand was subsequently treated with continuous positive airway pressure before he was discharged with 8 L home oxygen. With no current established medical therapy for HPS, the patient was assessed for liver transplantation and a decision was made in favour of this.
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Affiliation(s)
- Nahima Miah
- General Medicine, Medway Maritime Hospital, Gillingham, UK
| | - Aidan Ryan
- General Medicine, Medway Maritime Hospital, Gillingham, UK
| | | | - Mohamed Saleh
- Gastroenterology and Hepatology, Medway Maritime Hospital, Gillingham, UK
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Dahiya DS, Kichloo A, Shaka H, Singh J, Singh G, Wani F, Masudi S, Koul H, Pisipati S. Hepatopulmonary Syndrome: A Nationwide Analysis of Epidemiological Trends and Outcomes From 2012 to 2018. Gastroenterology Res 2021; 14:252-258. [PMID: 34527095 PMCID: PMC8425794 DOI: 10.14740/gr1448] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 08/13/2021] [Indexed: 11/11/2022] Open
Abstract
Background This study was designed to determine the epidemiological trends and adverse outcomes of hepatopulmonary syndrome (HPS). Methods This retrospective interrupted trend study analyzed data from the Nationwide Inpatient Sample (NIS) for the years 2012, 2014, 2016 and 2018 to identify adult (≥ 18 years) hospitalizations with a diagnosis of HPS. We highlighted epidemiological trends for HPS. Inpatient mortality, mean length of stay (LOS) and mean total hospital charge (THC) were estimated using multivariate regression trend analysis. Results We observed an increase in the total number of HPS hospitalizations from 1,565 in 2012 to 2,495 in 2018, with mean age ranging from 55.8 to 58.1 years. There was a trend towards increasing hospitalizations (P-trend < 0.001) with increasing mean age (P-trend = 0.003) for HPS. Whites made up most of the study population. The inpatient mortality for HPS ranged from 12.4% to 12.6%, but there was no statistically significant trend for mortality (P-trend = 0.534) between 2012 and 2018. Additionally, there was no change in both mean LOS (P-trend = 0.545) and mean THC (P-trend = 0.534) for HPS for these years. Conclusions Hospitalizations and mean age for HPS were on the rise. Inpatient mortality ranged from 12.4% to 12.6%; however, a statistically significant trend for mortality was absent.
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Affiliation(s)
- Dushyant Singh Dahiya
- Department of Internal Medicine, Central Michigan University College of Medicine, 1000 Houghton Ave, Saginaw, MI 48602, USA
| | - Asim Kichloo
- Department of Internal Medicine, Central Michigan University College of Medicine, 1000 Houghton Ave, Saginaw, MI 48602, USA.,Department of Internal Medicine, Samaritan Medical Center, Watertown, NY, USA
| | - Hafeez Shaka
- Department of Internal Medicine, John H. Stroger, Jr. Hospital of Cook County, 1969 Ogden Ave, Chicago, IL 60612, USA
| | - Jagmeet Singh
- Department of Internal Medicine, Guthrie Robert Packer Hospital, 1 Guthrie Square, Sayre, PA 18840, USA
| | - Gurdeep Singh
- Department of Internal Medicine and Endocrinology, Lady of Lourdes Memorial Hospital, 169 Riverside Dr, Binghamton, NY 13905, USA
| | - Farah Wani
- Department of Family Medicine, Samaritan Medical Center, 830 Washington St, Watertown, NY 13601, USA
| | - Sundas Masudi
- Department of Internal Medicine, University of Liverpool School of Medicine, Cedar House, Ashton St, Liverpool, L693GE, UK
| | - Hazique Koul
- Department of Internal Medicine, Jaharul Islam Medical College, Bajitpur, BD 2336, Bangladesh
| | - Sailaja Pisipati
- Department of Gastroenterology and Hepatology, Mayo Clinic, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
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Anesthetic Management Using Low Fraction of Inspiratory Oxygen for Living Donor Liver Transplantation in a Patient With Hepatopulmonary Syndrome Complicated by Interstitial Pneumonia: A Case Report. Transplant Proc 2021; 53:2556-2558. [PMID: 34465421 DOI: 10.1016/j.transproceed.2021.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Accepted: 08/07/2021] [Indexed: 11/24/2022]
Abstract
BACKGROUND Hepatopulmonary syndrome frequently complicates end-stage liver disease. It causes hypoxemia and requires oxygen administration. Additionally, interstitial pneumonia causes hypoxemia; however, it is known to be aggravated by high-concentration oxygen administration. CASE PRESENTATION A 71-year-old woman with hepatopulmonary syndrome and interstitial pneumonia underwent living donor liver transplantation, requiring conflicting management in terms of the inspiratory oxygen concentration. We achieved a low intraoperative fraction of inspiratory oxygen by increasing the cardiac output with intravenous catecholamines. As a result, the transplanted liver functioned well postoperatively, and the patient was discharged without exacerbation of the interstitial pneumonia. CONCLUSION We suggest that patients with hepatopulmonary syndrome complicated with interstitial pneumonia can undergo successful living donor liver transplantation without the use of high inspiratory oxygen concentration by using catecholamines to maintain a high mixed venous oxygen saturation.
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Raevens S, Boret M, De Pauw M, Fallon MB, Van Vlierberghe H. Pulmonary Abnormalities in Liver Disease: Relevance to Transplantation and Outcome. Hepatology 2021; 74:1674-1686. [PMID: 33636019 DOI: 10.1002/hep.31770] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/17/2021] [Accepted: 02/08/2021] [Indexed: 12/14/2022]
Abstract
Pulmonary disease in liver cirrhosis and portal hypertension (PH) constitutes a challenging clinical scenario and may have important implications with regard to prognosis, liver transplantation (LT) candidacy, and post-LT outcome. Pre-LT evaluation should include adequate screening for pulmonary diseases that may occur concomitantly with liver disease as well as for those that may arise as a complication of end-stage liver disease and PH, given that either may jeopardize safe LT and successful outcome. It is key to discriminate those patients who would benefit from LT, especially pulmonary disorders that have been reported to resolve post-LT and are considered "pulmonary indications" for transplant, from those who are at increased mortality risk and in whom LT is contraindicated. In conclusion, in this article, we review the impact of several pulmonary disorders, including cystic fibrosis, alpha 1-antitrypsin deficiency, hereditary hemorrhagic telangiectasia, sarcoidosis, coronavirus disease 2019, asthma, chronic obstructive pulmonary disease, pulmonary nodules, interstitial lung disease, hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension, on post-LT survival, as well as the reciprocal impact of LT on the evolution of lung function.
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Affiliation(s)
- Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
| | - Maxine Boret
- 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
| | - Michael B Fallon
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, AZ
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University-Ghent University Hospital, Ghent, Belgium
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Turine Neto P, Seda Neto J, da Fonseca EA, Porta G, Pugliese R, Benavides MAR, Vincenzi R, Roda KMO, Danesi VLB, Hirschfeld APM, Feier FH, Chapchap P, Miura IK. Impact of hypoxemia on pediatric liver transplantation for hepatopulmonary syndrome. Pediatr Transplant 2021; 25:e13968. [PMID: 33590638 DOI: 10.1111/petr.13968] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 11/20/2020] [Accepted: 12/27/2020] [Indexed: 01/03/2023]
Abstract
BACKGROUND The treatment of choice for patients with cirrhosis and HPS is LT. The clinical manifestations associated with hypoxemia result in limitations and a poor health-related quality of life of affected patients. The present report aims to study the differences in outcomes between patients with PaO2 < 50 mm Hg and those with PaO2 ≥ 50 mm Hg. METHODS This was a retrospective study of 21 patients under 18 years of age conducted from 2001 to 2018; the patients were divided into 2 groups: G1-PaO2 ≥ 50 mm Hg, 11 patients, and G2-PaO2 < 50 mm Hg, 10 patients. Demographic, clinical, laboratory, and perioperative data; outcome variables; and post-transplant survival were compared between the groups. RESULTS In total, 2/11 (18.2%) patients in G1 and 8/10 (80%) patients in G2 required supplemental oxygen therapy at home (P = .005). Patients in G2 required prolonged MV (median 8.5 days in G2 vs 1 day in G1, P = .015) and prolonged ICU and hospital stays (P = .002 and P = .001, respectively). Oxygen weaning time was longer in G2 (median 127.5 days) than in G1 (median 3 days; P = .004). One (9.1%) patient in G1 and three (30%) patients in G2 died (P = .22). The survival at 90 months was 90.9% in G1 and 70% in G2 (P = .22). CONCLUSION The survival between groups was similar. Patients with very severe HPS required a longer MV time, longer ICU and hospital stays, and a longer O2 weaning time than those with mild, moderate, or severe HPS.
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Affiliation(s)
- Plínio Turine Neto
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - João Seda Neto
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Eduardo Antunes da Fonseca
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Gilda Porta
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Renata Pugliese
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Marcel Albeiro Ruiz Benavides
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Rodrigo Vincenzi
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Karina Moreira Oliveira Roda
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Vera Lúcia Baggio Danesi
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Adriana Porta Miche Hirschfeld
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Flavia Heinz Feier
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Paulo Chapchap
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
| | - Irene Kazue Miura
- Hepatology and Liver Transplantation, Hospital Sírio-Libanês, São Paulo, Brazil.,Hepatology and Liver Transplantation A. C. Camargo Cancer Center, São Paulo, Brazil.,Hospital Municipal Infantil Menino Jesus, São Paulo, Brazil
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Aragon Pinto C, Iyer VN, Albitar HAH, Anderson A, Cajigas H, Simonetto DA, Krowka MJ, DuBrock HM, Gallo de Moraes A. Outcomes of liver transplantation in patients with hepatopulmonary syndrome in the pre and post-MELD eras: A systematic review. Respir Med Res 2021; 80:100852. [PMID: 34418867 DOI: 10.1016/j.resmer.2021.100852] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/15/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The lack of large hepatopulmonary syndrome cohorts undergoing liver transplantation (LT) has resulted in limited information about post-LT outcomes and expectations. METHODS The long and short-term outcomes of LT in patients with hepatopulmonary syndrome (HPS) were evaluated before and after the implementation of Model for Endstage Liver Disease (MELD) score in 2002, granting exception points for patients with HPS. PubMed/Medline, Embase, Web of Science and Scopus databases were searched for published and unpublished studies from 01/1990 to 04/2019. Studies that included HPS patients who underwent LT and reported post-LT outcomes and HPS severity were reviewed. After reviewing the full text of 1421 articles, 30 were included in the pre-MELD era (before 2002) and 60 in the post-MELD era. RESULTS A total of 598 patients (210 children and 388 adults) with HPS who underwent LT were included in this systematic review. In children, 5-year survival probability was similar in the pre and post-MELD groups (85.7% vs. 97.4; p = 0.09). Median post-transplant PaO2 in room air was higher in the post-MELD group (71 [53-87] vs. 97 [80-108] mmHg: p = 0.008). In adults, 5-year survival probability was higher in the post-MELD era (73 vs. 87.3%; p = 0.008). Median post-transplant PaO2 in room air was higher in post-MELD group (75 [63-85] vs. 87 [75-95] mmHg; p = 0.001).. CONCLUSIONS After MELD exception implementation, survival rates and post-transplant oxygenation improved in adult patients with HPS who underwent liver transplantation, whereas only post-transplant oxygenation improved in children.
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Affiliation(s)
- Catarina Aragon Pinto
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Epidemiology and Translational Research in Intensive Care group (METRIC), Mayo Clinic, Rochester, MN, USA
| | - Vivek N Iyer
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Alexandra Anderson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Hector Cajigas
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Hilary M DuBrock
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Epidemiology and Translational Research in Intensive Care group (METRIC), Mayo Clinic, Rochester, MN, USA.
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Han SK, Kim MY, Kang SH, Suk KT, Baik SK. Hepatopulmonary syndrome is related to the development of acute-on-chronic liver failure and poor prognosis in cirrhotic patients. Hepatol Int 2021; 15:1207-1214. [PMID: 34319553 DOI: 10.1007/s12072-021-10226-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2021] [Accepted: 06/11/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND AND AIMS Long-term prospective data on hepatopulmonary syndrome (HPS) from a large number of patients, especially in Asian patients, are lacking. We evaluated the long-term prognosis of HPS and the development of acute-on-chronic liver failure (ACLF), and related factors. METHODS A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography for the diagnosis of HPS were enrolled and observed prospectively from 2014 to 2019. RESULTS A total of 59 patients (41%) were diagnosed with HPS (24 grade 1, 23 grade 2, 12 grade 3). Thirty-eight and 37 patients died in the HPS and non-HPS groups, respectively (p < 0.01). The 5-year survival rate was 47% in the HPS group and 62% in the non-HPS group. In the Cox proportional hazards model, HPS and Model for End-stage Liver Disease (MELD) score ≥ 18, and Child-Turcotte-Pugh (CTP) class B/C were significant risk factors for mortality after adjusting for other risk factors (HPS hazard ratio [HR] = 1.9, p = 0.01; MELD score ≥ 18 HR = 2.3, p < 0.01; CTP class B/C HR = 2.9, p < 0.01). Compared to that in non-HPS group, the HPS group had a significantly higher incidence of ACLF during follow-up (p < 0.01) and more frequently presented with lung involvement of ACLF (p = 0.03). CONCLUSIONS In the long-term follow-up cohort, patients with HPS showed poorer prognosis than that of patients without HPS. HPS was a risk factor for ACLF development independent of hepatic dysfunction, and lung involvement was significantly common than without ACLF.
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Affiliation(s)
- Seul Ki Han
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsanro, Wonju, 26426, Republic of Korea
| | - Moon Young Kim
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsanro, Wonju, 26426, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Seong Hee Kang
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsanro, Wonju, 26426, Republic of Korea.,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
| | - Ki Tae Suk
- Department of Internal Medicine, Hanllym University College of Medicine, Chuncheon, South Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, 20, Ilsanro, Wonju, 26426, Republic of Korea. .,Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. .,Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
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Ji W, Nie M, Mao JF, Zhang HB, Wang X, Wu XY. Growth hormone cocktail improves hepatopulmonary syndrome secondary to hypopituitarism: A case report. World J Clin Cases 2021; 9:4852-4858. [PMID: 34222458 PMCID: PMC8223853 DOI: 10.12998/wjcc.v9.i18.4852] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 04/02/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Metabolic associated fatty liver disease frequently occurs in patients with hypopituitarism and growth hormone (GH) deficiency. Some patients may develop to hepatopulmonary syndrome (HPS). HPS has a poor prognosis and liver transplantation is regarded as the only approach to cure it.
CASE SUMMARY A 29-year-old man presented with progressive dyspnea for 1 mo. At the age of 10 years, he was diagnosed with panhypopituitarism associated with pituitary stalk interruption syndrome. Levothyroxine and hydrocortisone were given since then. To achieve ideal height, he received GH treatment for 5 years. The patient had an oxygen saturation of 78% and a partial pressure of arterial oxygen of 37 mmHg with an alveolar–arterial oxygen gradient of 70.2 mmHg. Abdominal ultrasonography showed liver cirrhosis and an enlarged spleen. Perfusion lung scan demonstrated intrapulmonary arteriovenous right-to-left shunt. HPS (very severe) was our primary consideration. His hormonal evaluation revealed GH deficiency and hypogonadotropic hypogonadism when thyroid hormone, cortisol, and desmopressin were administrated. After adding with long-acting recombinant human GH and testosterone for 14 mo, his liver function and hypoxemia were improved and his progressive liver fibrosis was stabilized. He was off the waiting list of liver transplantation.
CONCLUSION Clinicians should screen HPS patients' anterior pituitary function as early as possible and treat them primarily with GH cocktail accordingly.
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Affiliation(s)
- Wen Ji
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Min Nie
- Department of Endocrinology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Jiang-Feng Mao
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Hong-Bing Zhang
- Department of Physiology, Collaborative Innovation Center for Cancer Medicine, Institute of Basic Medical Sciences and School of Basic Medicine, Beijing 100005, China
| | - Xi Wang
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Xue-Yan Wu
- Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
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Keelan E, Ferguson C, Kerr R. When common things aren't so common: A case report of hepatopulmonary syndrome. Clin Med (Lond) 2021; 21:226-227. [PMID: 34001574 DOI: 10.7861/clinmed.2021-0142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
A 60-year-old smoker with a history of liver cirrhosis and chronic obstructive pulmonary syndrome (COPD) presented with hypoxic respiratory failure. This was felt secondary to an exacerbation of COPD. Despite treatment, the patient required 10 L of oxygen to achieve saturations of 88% on ambulation. Interstitial lung disease, pulmonary emboli and pulmonary hypertension were excluded as potential aetiologies of hypoxia. Given the history of cirrhosis, hepatopulmonary syndrome was postulated. Contrast echocardiography suggested an extracardiac shunt; a technetium-99m macroaggregated albumin scan confirmed the diagnosis.
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Zhu J, Qiu J, Chen K, Wang W, Zheng S. Tea polyphenols and Levofloxacin alleviate the lung injury of hepatopulmonary syndrome in common bile duct ligation rats through Endotoxin -TNF signaling. Biomed Pharmacother 2021; 137:111263. [PMID: 33516071 DOI: 10.1016/j.biopha.2021.111263] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 01/06/2021] [Accepted: 01/07/2021] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND & AIMS Hepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and arterial blood oxygen desaturation in patients with chronic liver disease. Generally, common bile duct ligation (CBDL) rats are a suitable experimental model for studying hepatopulmonary syndrome. Our previous study demonstrated that endotoxin surges markedly, followed by bacterial translocation and the loss of liver immune function in all the stages of CBDL, thereby contributing to the pathogenesis of HPS. However, the mechanisms behind the increase of the endotoxin and how to alleviate it have not yet been elucidated. Pulmonary injury induced by increased bilirubin, endotoxin, and inflammatory mediators occurs in the early and later stages of CBDL. This study assessed the effects of Tea polyphenols (TP) and Levofloxacin on endotoxin reduction and suppression of lung injury in HPS rats in the long and short term, respectively. METHODS Morphological change of pulmonary injury, HPS relative index, endotoxin concentration, and the activation extent of Malondialdehyde (MDA) and Myeloperoxidase (MPO) were evaluated in CBDL rats with or without TP and Levofloxacin for three weeks or six weeks. The inflammation factors of serum, lung tissue, and BALF were then compared at the same condition for the two time periods. This was followed by adoption of the network pharmacology approach, which was mainly composed of active component gathering, target prediction, HPS gene collection, network analysis, and gene enrichment analysis. Finally, the mRNA and protein levels of the inflammatory factors were studied and relative signaling expression was assessed using RT-PCR and Western blot analysis. RESULTS The obtained results indicated that the pulmonary injury manifestation was perceived and endotoxin, MDA, and MPO activation were markedly increased in the early and later stages of CBDL. TP and Levofloxacin treatment alleviated endotoxin infection and inflammation factor expression three weeks and six weeks after CBDL. In addition, Levofloxacin displayed a short time anti-bacterial effect, while TP exerted a long period function. TP and Levofloxacin also reduced TNF-α, TGF-β, IL-1β, PDGF-BB, NO, ICAM-1, and ET-1 expression on the mRNA or protein expression. With regard to the pharmacological mechanism, the network analysis indicated that 12 targets might be the therapeutic targets of TP and Levofloxacin on HPS, namely ET-1, NOs3, VEGFa, CCl2, TNF, Ptgs2, Hmox1, Alb, Ace, Cav1, and Mmp9. The gene enrichment analysis implied that TP and Levofloxacin probably benefited patients with HPS by modulating pathways associated with the AGE-RAGE signaling pathway, the TNF signaling pathway, the HIF-1 signaling pathway, the VEGF signaling pathway, and the IL-17 signaling pathway, Rheumatoid arthritis, Fluid shear stress, and atherosclerosis. Finally, the TNF-α level was mainly diminished on the protein level following CBDL. CONCLUSIONS TP and Levofloxacin could alleviate pulmonary injury for short and long period, respectively, while at the same time preventing endotoxin and the development of HPS in CBDL rats. These effects are possibly associated with the regulation of the Endotoxin -TNF-α pathways.
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Affiliation(s)
- Jiyun Zhu
- Hepatobiliary Surgery Department, Ningbo First Hospital, Ningbo, People's Republic of China
| | - Jiangfeng Qiu
- Department of Gastrointestinal Surgery, Shanghai Renji Hospital Affiliated to Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China
| | - Kaibo Chen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People's Republic of China
| | - Wenbo Wang
- Hepatobiliary Surgery Department, Ningbo First Hospital, Ningbo, People's Republic of China.
| | - Siming Zheng
- Hepatobiliary Surgery Department, Ningbo First Hospital, Ningbo, People's Republic of China
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Russell-Jones E, Grammatikopoulos T, Greenough A, Dhawan A, Dassios T. Non-invasive assessment of intrapulmonary shunt and ventilation to perfusion ratio in children with hepatopulmonary syndrome before and after liver transplantation. Respir Med 2021; 180:106372. [PMID: 33780759 DOI: 10.1016/j.rmed.2021.106372] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2020] [Accepted: 03/16/2021] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To use the oxyhaemoglobin dissociation curve (ODC) to non-invasively measure the ventilation perfusion ratio (VA/Q) and right-to-left intrapulmonary vascular shunt before and after liver transplantation (LT) in children with hepatopulmonary syndrome (HPS). To investigate whether the right-to-left shunt derived by ODC correlated with the shunt derived by technetium-99 labelled macroaggregated albumin lung perfusion scan (MAA). METHODS A retrospective cohort study at King's College Hospital NHS Foundation Trust, London, UK was performed between 1998 and 2016. The VA/Q and right-to-left shunt were non-invasively measured pre and post LT. The pre-LT right-to-left intrapulmonary shunt was also measured by MAA. The non-invasively derived pre-LT shunt was correlated with the shunt derived by MAA. RESULTS Fifteen children with HPS were studied with a median (IQR) age at LT of 8.8 (6.6-12.9) years. The median (IQR) pre-LT VA/Q [0.49 (0.42-0.65)] was lower compared to the post-LT VA/Q [0.61 (IQR 0.54-0.72), p = 0.012]. The median (IQR) pre-LT shunt was 19 (3-24) % which decreased to zero in all but one children post-LT, (p = 0.001). The MAA-derived shunt was significantly positively correlated with the ODC-derived shunt (r = 0.783, p = 0.001). The mean (SD) difference between shunt derived by ODC and shunt derived by MAA was 0.5 (7.2) %. CONCLUSIONS Ventilation/perfusion impairment reverses but not completely resolves after liver transplantation in children with hepatopulmonary syndrome. The non-invasive method for estimating intrapulmonary shunting could be used as an alternative to the macroaggregated albumin scan in this population.
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Affiliation(s)
- Emma Russell-Jones
- Paediatric Liver, GI & Nutrition Centre and Mowat Labs, King's College Hospital, London, SE5 9RS, United Kingdom.
| | - Tassos Grammatikopoulos
- Paediatric Liver, GI & Nutrition Centre and Mowat Labs, King's College Hospital, London, SE5 9RS, United Kingdom; Institute of Liver Studies, King's College London, London, SE5 9RS, United Kingdom.
| | - Anne Greenough
- Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, SE5 9RS, United Kingdom; Asthma UK Centre for Allergic Mechanisms in Asthma, King's College London, London, SE1 9RT, United Kingdom; NIHR Biomedical Centre at Guy's and St Thomas NHS Foundation Trust, King's College London, London, SE1 9RT, United Kingdom.
| | - Anil Dhawan
- Paediatric Liver, GI & Nutrition Centre and Mowat Labs, King's College Hospital, London, SE5 9RS, United Kingdom; Institute of Liver Studies, King's College London, London, SE5 9RS, United Kingdom.
| | - Theodore Dassios
- Department of Women and Children's Health, School of Life Course Sciences, Faculty of Life Sciences and Medicine, King's College London, London, SE5 9RS, United Kingdom; NIHR Biomedical Centre at Guy's and St Thomas NHS Foundation Trust, King's College London, London, SE1 9RT, United Kingdom; Neonatal Intensive Care Centre, King's College Hospital NHS Foundation Trust, London, SE5 9RS, United Kingdom.
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Mendoza N, Rivas E, Rodriguez-Roisin R, Garcia T, Bruguera M, Agusti A, Faner R. Liver epigenome changes in patients with hepatopulmonary syndrome: A pilot study. PLoS One 2021; 16:e0245046. [PMID: 33630849 PMCID: PMC7906328 DOI: 10.1371/journal.pone.0245046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 12/22/2020] [Indexed: 11/25/2022] Open
Abstract
The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.
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Affiliation(s)
- Nuria Mendoza
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Eva Rivas
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Department of Anesthesia, Hospital Clinic, Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
| | - Roberto Rodriguez-Roisin
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Tamara Garcia
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Miquel Bruguera
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Alvar Agusti
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Rosa Faner
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- * E-mail:
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Kim KY, Kim TH, Lee JM, Yi NJ, Kim HY, Moon JS, Ko JS. Clinical outcomes and risk factors of hepatopulmonary syndrome in children. Sci Rep 2021; 11:4134. [PMID: 33603173 PMCID: PMC7892858 DOI: 10.1038/s41598-021-83785-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Accepted: 02/08/2021] [Indexed: 12/24/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is defined as three distinct features: liver disease, hypoxemia, and intrapulmonary vasodilation. The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia (BA). We performed a retrospective cohort study of all children who were diagnosed with HPS between 2000 and 2018 at Seoul National University Hospital. The clinical features and outcomes of the 10 patients diagnosed with HPS were reviewed. To clarify the risk factors of HPS in patients with BA, we reviewed 120 patients diagnosed with BA. Underlying liver disease was BA in 8 patients, portal vein agenesis in 1 patient, and portal vein thrombosis in 1 patient. A total of 7 patients underwent liver transplantation (LT). Currently, all seven patients, including 3 patients with severe HPS, survived after LT. The prevalence of HPS in children with BA was 7%. Polysplenia/interrupted inferior vena was the only risk factor for HPS in BA patients in multivariate analysis. The Pediatric End-Stage Liver Disease score was not associated with the development of HPS. Children with severe HPS undergoing LT had excellent outcomes. Screening for HPS in children with BA is required regardless of the severity of liver diseases.
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Affiliation(s)
- Kwang Yeon Kim
- Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-Gu, Seoul, 110-769, Korea
| | - Tae Hyeong Kim
- Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-Gu, Seoul, 110-769, Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun-Young Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jin Soo Moon
- Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-Gu, Seoul, 110-769, Korea
| | - Jae Sung Ko
- Department of Pediatrics, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-Gu, Seoul, 110-769, Korea.
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