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Qasim A, Jyala A, Shrivastava S, Allena N, Ghazanfar H, Bhatt V, Ali HR, Vakde T, Patel H. Hepatopulmonary Syndrome: A Comprehensive Review. Cureus 2024; 16:e65204. [PMID: 39176346 PMCID: PMC11340781 DOI: 10.7759/cureus.65204] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/23/2024] [Indexed: 08/24/2024] Open
Abstract
Hepatopulmonary syndrome (HPS) is defined by abnormally dilated blood vessels and shunts within the lungs, leading to impaired oxygen exchange. This condition results from intricate interactions between the liver, the gastrointestinal system, and the lungs. This complex system primarily affects pulmonary endothelial, immunomodulatory, and respiratory epithelial cells. Consequently, this contributes to pathological pulmonary changes characteristic of HPS. A classification system based on the severity of oxygen deficiency has been proposed for grading the physiological dysfunction of HPS. Contrast-enhanced echocardiography is considered the primary radiological evaluation for identifying abnormal blood vessel dilations within the lungs, which, combined with an elevated alveolar-arterial gradient, is essential for making the diagnosis. Liver transplantation is the sole effective definitive treatment that can reverse the course of the condition. Despite often being symptomless, HPS carries a significant risk of mortality before transplantation, regardless of the severity of liver disease. Meanwhile, there is varying data regarding survival rates following liver transplantation. The adoption of the model for end-stage liver disease (MELD) standard exception policy has notably improved the results for individuals with HPS compared to the period before MELD was introduced. This review offers a summary of the present understanding, highlighting recent advancements in the diagnosis and treatment of HPS. Furthermore, it aims to augment comprehension of the condition's fundamental mechanisms through insights derived from experimental models and translational research.
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Affiliation(s)
- Abeer Qasim
- Internal Medicine, BronxCare Health System, New York, USA
| | | | | | - Nishant Allena
- Pulmonary Medicine, BronxCare Health System, New York, USA
| | | | | | - Husnain R Ali
- Medicine, American University of the Caribbean School of Medicine, Miramar, USA
| | - Trupti Vakde
- Pulmonary and Critical Care, BronxCare Health System, New York, USA
| | - Harish Patel
- Internal Medicine, BronxCare Health System, New York, USA
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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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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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Ho APT, Tjønnfjord EB, Schreiner C, Sørensen OHS, Iqbal N, Stavem K, Saberniak J. A woman in her fifties with cirrhosis of the liver and postural dyspnoea. TIDSSKRIFT FOR DEN NORSKE LEGEFORENING 2023; 143:22-0754. [PMID: 37830965 DOI: 10.4045/tidsskr.22.0754] [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: 10/14/2023] Open
Abstract
A woman in her fifties with advanced cirrhosis of the liver was admitted multiple times with recurrent pleural effusion and ascites. She was accepted for liver transplantation, at which time she developed postural dyspnoea and a drop in oxygen saturation.
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Affiliation(s)
| | - Eirik Brekka Tjønnfjord
- Trombosepoliklinikken, Sykehuset Østfold Kalnes, og, Oslo universitetssykehus, Rikshospitalet
| | | | | | - Naveed Iqbal
- Avdeling for hjertesykdommer, Akershus universitetssykehus
| | - Knut Stavem
- Lungeavdelingen, Akershus universitetssykehus, og, Institutt for klinisk medisin, Universitetet i Oslo
| | - Jørg Saberniak
- Avdeling for hjertesykdommer, Akershus universitetssykehus
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5
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Lawton E, Holmes‐Liew C. A rare case of common variable immunodeficiency and hepatopulmonary syndrome. Respirol Case Rep 2022; 10:e0898. [PMID: 35028155 PMCID: PMC8737112 DOI: 10.1002/rcr2.898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/09/2021] [Accepted: 12/13/2021] [Indexed: 11/21/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is the triad of liver disease, hypoxia and intrapulmonary shunt. In this case report, we describe an immunocompromised female with a background of common variable immunodeficiency (CVID) who presented with haemoptysis and dyspnoea. Investigations demonstrated significant hypoxaemia and intrapulmonary right-to-left shunting. Further evidence revealed advanced liver cirrhosis, and a diagnosis of HPS was made. This extremely rare association of CVID and HPS is one of the few cases reported in the literature.
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Affiliation(s)
- Emily Lawton
- Thoracic MedicineRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
- School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
| | - Chien‐Li Holmes‐Liew
- Thoracic MedicineRoyal Adelaide HospitalAdelaideSouth AustraliaAustralia
- School of MedicineUniversity of AdelaideAdelaideSouth AustraliaAustralia
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6
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Orthodeoxia and its implications on awake-proning in COVID-19 pneumonia. Crit Care 2021; 25:429. [PMID: 34915916 PMCID: PMC8674521 DOI: 10.1186/s13054-021-03859-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 12/06/2021] [Indexed: 11/26/2022] Open
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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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8
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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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10
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Gupta S, Tang R, Al-Hesayen A. Inhaled nitric oxide improves the hepatopulmonary syndrome: a physiologic analysis. Thorax 2021; 76:1142-1145. [PMID: 33859047 DOI: 10.1136/thoraxjnl-2020-216128] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 12/10/2020] [Accepted: 03/05/2021] [Indexed: 01/30/2023]
Abstract
The hepatopulmonary syndrome (HPS) is defined by liver dysfunction, intrapulmonary vasodilatation and abnormal oxygenation. Hypoxaemia is progressive and liver transplant is the only effective treatment. Severe hypoxaemia is a life-threatening HPS complication, particularly after transplant. We evaluated gas-exchange and haemodynamic effects of invasive therapies in a consecutive sample of 26 pre-transplant patients. Inhaled nitric oxide significantly improved partial pressure of oxygen (12.4 mm Hg; p=0.001) without deleterious effects on cardiac output. Trendelenburg positioning resulted in a small improvement, and methylene blue did not, though individual responses were variable. Future studies should prospectively evaluate these strategies in severe post-transplant hypoxaemia.
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Affiliation(s)
- Samir Gupta
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada .,Division of Respirology, St Michael's Hospital, Toronto, Ontario, Canada.,Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Ontario, Canada
| | - Rosalind Tang
- Keenan Research Centre for Biomedical Science, St Michael's Hospital, Toronto, Ontario, Canada.,Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK
| | - Abdul Al-Hesayen
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Cardiology, St Michael's Hospital, Toronto, Ontario, Canada
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11
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Busana M, Giosa L, Cressoni M, Gasperetti A, Di Girolamo L, Martinelli A, Sonzogni A, Lorini L, Palumbo MM, Romitti F, Gattarello S, Steinberg I, Herrmann P, Meissner K, Quintel M, Gattinoni L. The impact of ventilation-perfusion inequality in COVID-19: a computational model. J Appl Physiol (1985) 2021; 130:865-876. [PMID: 33439790 PMCID: PMC8083177 DOI: 10.1152/japplphysiol.00871.2020] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
COVID-19 infection may lead to acute respiratory distress syndrome (CARDS) where severe gas exchange derangements may be associated, at least in the early stages, only with minor pulmonary infiltrates. This may suggest that the shunt associated to the gasless lung parenchyma is not sufficient to explain CARDS hypoxemia. We designed an algorithm (VentriQlar), based on the same conceptual grounds described by J.B. West in 1969. We set 498 ventilation-perfusion (VA/Q) compartments and, after calculating their blood composition (PO2, PCO2, and pH), we randomly chose 106 combinations of five parameters controlling a bimodal distribution of blood flow. The solutions were accepted if the predicted PaO2 and PaCO2 were within 10% of the patient's values. We assumed that the shunt fraction equaled the fraction of non-aerated lung tissue at the CT quantitative analysis. Five critically-ill patients later deceased were studied. The PaO2/FiO2 was 91.1 ± 18.6 mmHg and PaCO2 69.0 ± 16.1 mmHg. Cardiac output was 9.58 ± 0.99 L/min. The fraction of non-aerated tissue was 0.33 ± 0.06. The model showed that a large fraction of the blood flow was likely distributed in regions with very low VA/Q (Qmean = 0.06 ± 0.02) and a smaller fraction in regions with moderately high VA/Q. Overall LogSD, Q was 1.66 ± 0.14, suggestive of high VA/Q inequality. Our data suggest that shunt alone cannot completely account for the observed hypoxemia and a significant VA/Q inequality must be present in COVID-19. The high cardiac output and the extensive microthrombosis later found in the autopsy further support the hypothesis of a pathological perfusion of non/poorly ventilated lung tissue.NEW & NOTEWORTHY Hypothesizing that the non-aerated lung fraction as evaluated by the quantitative analysis of the lung computed tomography (CT) equals shunt (VA/Q = 0), we used a computational approach to estimate the magnitude of the ventilation-perfusion inequality in severe COVID-19. The results show that a severe hyperperfusion of poorly ventilated lung region is likely the cause of the observed hypoxemia. The extensive microthrombosis or abnormal vasodilation of the pulmonary circulation may represent the pathophysiological mechanism of such VA/Q distribution.
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Affiliation(s)
- Mattia Busana
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Lorenzo Giosa
- Department of Surgical Science, University of Turin, Italy
| | - Massimo Cressoni
- Unit of Radiology, IRCCS Policlinico San Donato, San Donato, Italy
| | - Alessio Gasperetti
- Department of Cardiology, IRCCS Cardiologico Monzino, San Donato Milanese, Italy
| | - Luca Di Girolamo
- Department of Intensive Care Medicine, IRCCS Policlinico San Donato, San Donato Milanese, Italy
| | | | - Aurelio Sonzogni
- ASST Papa Giovanni XXIII, Department of Pathology, Bergamo, Italy
| | - Luca Lorini
- ASST Papa Giovanni XXIII, Department of Intensive Care Medicine, Bergamo, Italy
| | - Maria Michela Palumbo
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Federica Romitti
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Simone Gattarello
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Irene Steinberg
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Peter Herrmann
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Konrad Meissner
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Michael Quintel
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
| | - Luciano Gattinoni
- Department of Anesthesiology, Intensive Care and Emergency Medicine, University Medical Center of Göttingen, Göttingen, Germany
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12
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Benz F, Mohr R, Tacke F, Roderburg C. Pulmonary Complications in Patients with Liver Cirrhosis. J Transl Int Med 2020; 8:150-158. [PMID: 33062591 PMCID: PMC7534492 DOI: 10.2478/jtim-2020-0024] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023] Open
Abstract
Patients with advanced chronic liver diseases, particularly with decompensated liver cirrhosis, can develop specific pulmonary complications independently of any pre-existing lung disease. Especially when dyspnea occurs in combination with liver cirrhosis, patients should be evaluated for hepato-pulmonary syndrome (HPS), porto-pulmonary hypertension (PPHT), hepatic hydrothorax and spontaneous bacterial empyema, which represent the clinically most relevant pulmonary complications of liver cirrhosis. Importantly, the pathophysiology, clinical features, diagnosis and the corresponding therapeutic options differ between these entities, highlighting the role of specific diagnostics in patients with liver cirrhosis who present with dyspnea. Liver transplantation may offer a curative therapy, including selected cases of HPS and PPHT. In this review article, we summarize the pathogenesis, clinical features, diagnostic algorithms and treatment options of the 4 specific pulmonary complications in patients with liver cirrhosis.
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Affiliation(s)
- Fabian Benz
- Charité University Medicine Berlin, Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany
| | - Raphael Mohr
- Charité University Medicine Berlin, Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany
| | - Frank Tacke
- Charité University Medicine Berlin, Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany
| | - Christoph Roderburg
- Charité University Medicine Berlin, Department of Hepatology & Gastroenterology, Campus Virchow Klinikum and Campus Charité Mitte, Berlin, Germany
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13
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Khiangte B, Kothakota SR, Sasidharan M, Kareem H, Joshi S, Kumar VV, Kanala JR, Kumar C P, Nair AK. Prevalence and determinants of hepatopulmonary syndrome in decompensated chronic liver disease. Indian J Gastroenterol 2020; 39:362-369. [PMID: 32839954 DOI: 10.1007/s12664-020-01052-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2019] [Accepted: 05/07/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND One of the severe complications of liver disease is hepatopulmonary syndrome (HPS). There is paucity in literature regarding the various factors associated with the development of HPS. This study was conducted to analyze the prevalence and determinants of HPS among patients with decompensated chronic liver disease (CLD). METHODS This study was a cross-sectional-observational study conducted in a tertiary care center. Decompensated CLD patients admitted for pre-liver transplant workup were included in the study. Demographic data, clinical findings, and biochemical and hematologic parameters were collected. Pulse oximetry, arterial blood gas analysis, bubble contrast echocardiogram, diffusion capacity of the lungs for carbon monoxide (DLCO), and spirometry were done to get the needed parameters. All data were entered into a Microsoft Excel sheet and analyzed using the statistical software SPSS for Windows, version 22.0. RESULTS Among 64 subjects, 58 were men (90.6%). Mean age was 54.5 years. HPS was present in 26 (40.6%) patients. Platypnea and orthodeoxia were present more often in HPS patients. DLCO was significantly impaired among patients with HPS. Portopulmonary hypertension was seen in 8 (12.5%) subjects with no difference between HPS and non-HPS patients. Subjects with HPS had more severe liver disease. A model for end-stage liver disease (MELD)-Na score > 19 was associated with HPS (sensitivity 73.08%, specificity 65.79%, PPV 59.4%, and NPV 78.1%). Multivariate analysis (binary logistic regression) revealed that a higher MELD-Na score, hepatic encephalopathy, and impaired DLCO were independently associated with HPS. CONCLUSIONS HPS is associated with more severe liver disease (as per Child-Turcotte-Pugh [CTP] stage and MELD-Na score). There was no relation between HPS and causes of CLD. Higher MELD-Na score, hepatic encephalopathy, impaired DLCO, clubbing, and spider naevi were independently associated with HPS.
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Affiliation(s)
- Benjamine Khiangte
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Sunil Raviraj Kothakota
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India.
| | - Madhu Sasidharan
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Harish Kareem
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Subhashchandra Joshi
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Vijosh V Kumar
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Jagadeswara Reddy Kanala
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Praveen Kumar C
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
| | - Ajith K Nair
- Department of Gastroenterology, Kerala Institute of Medical Sciences (KIMS) Hospital, Anayara PO, Trivandrum, 695 029, India
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14
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Sangro B, Chan SL, Meyer T, Reig M, El-Khoueiry A, Galle PR. Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol 2020; 72:320-341. [PMID: 31954495 PMCID: PMC7779342 DOI: 10.1016/j.jhep.2019.10.021] [Citation(s) in RCA: 190] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/23/2019] [Accepted: 10/30/2019] [Indexed: 12/14/2022]
Abstract
Immune checkpoint inhibitors (ICIs) have reshaped cancer therapy. ICIs enhance T cell activation through various mechanisms and may help reverse the exhausted phenotype of tumour-infiltrating lymphocytes. However, disrupting the key role that checkpoint molecules play in immune homeostasis may result in autoimmune complications. A broad range of immune-related adverse events (irAEs) involve almost every organ but mostly affect the skin, digestive system, lung, endocrine glands, nervous system, kidney, blood cells, and musculoskeletal system. They are usually manageable but can be life-threatening. The incidence of irAEs is not very different in patients with hepatocellular carcinoma (HCC) compared to other tumour types, although there is a trend towards a higher incidence of hepatic irAEs. HCC usually develops on a background of cirrhosis with associated systemic manifestations. Extrahepatic organ dysfunction in cirrhosis may cause signs and symptoms that overlap with irAEs or increase their severity. Available guidelines for the management of irAEs have not specifically considered the assessment of toxicities in the context of patients with liver cancer and cirrhosis. This review addresses the toxicity profile of ICIs in patients with HCC, focusing on the challenges that the underlying liver disease poses to their diagnosis and management. Challenges include late recognition, inadequate work-up and delayed treatment, overdiagnosis and inappropriate interruption of ICIs, complications caused by immunosuppressive therapy, and increased cost. A specific algorithm for the management of hepatic irAEs is provided.
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Affiliation(s)
- Bruno Sangro
- Liver Unit, Clinica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain.
| | - Stephen L. Chan
- State Key Laboratory of Translational Oncology, Department of Clinical Oncology,Sir YK Pao Centre for Cancer, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Tim Meyer
- Royal Free London NHS Foundation Trust and UCL Cancer Institute, London, UK
| | - María Reig
- Barcelona Clinic Liver Cancer Group, Liver Unit, Hospital Clinic, IDIBAPS, University of Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Anthony El-Khoueiry
- University of Southern California, Keck School of Medicine, USC Norris Comprehensive Cancer Center, Los Angeles, CA, USA
| | - Peter R. Galle
- I. Medical Department, University Medical Center, Mainz, Germany
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15
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Sepehrinezhad A, Dehghanian A, Rafati A, Ketabchi F. Impact of liver damage on blood-borne variables and pulmonary hemodynamic responses to hypoxia and hyperoxia in anesthetized rats. BMC Cardiovasc Disord 2020; 20:13. [PMID: 31931715 PMCID: PMC6956555 DOI: 10.1186/s12872-019-01297-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Accepted: 12/05/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Liver disorders may be associated with normal pulmonary hemodynamic, hepatopulmonary syndrome (HPS), or portopulmonary hypertension (POPH). In this study, we aimed to investigate the effect of the severity of liver dysfunctions on blood-borne variables, and pulmonary hemodynamic during repeated ventilation with hyperoxic and hypoxic gases. METHODS Female Sprague Dawley rats were assigned into four groups of Sham (n = 7), portal vein ligation (PPVL, n = 7), common bile duct ligation (CBDL, n = 7), and combination of them (CBDL+ PPVL, n = 7). Twenty-eight days later, right ventricular systolic pressure (RVSP) and systemic blood pressure were recorded in anesthetized animals subjected to repeated maneuvers of hyperoxia (O2 50%) and hypoxia (O2 10%). Besides, we assessed blood parameters and liver histology. RESULTS Liver histology score, liver enzymes, WBC and plasma malondialdehyde in the CBDL+PPVL group were higher than those in the CBDL group. Also, the plasma platelet level in the CBDL+PPVL group was lower than those in the other groups. On the other hand, the serum estradiol in the CBDL group was higher than that in the CBDL+PPVL group. All the above parameters in the PPVL group were similar to those in the Sham group. During ventilation with hyperoxia gas, RVSP in the CBDL+PPVL group was higher than the ones in the other groups, and in the CBDL group, it was more than those in the PPVL and Sham groups. Hypoxic pulmonary vasoconstriction (HPV) was not detected in both CBDL+PPVL and CBDL groups, whereas, it retained in the PPVL group. CONCLUSION Severe liver damage increases RVSP in the CBDL+PPVL group linked to the high level of ROS, low levels of serum estradiol and platelets or a combination of them. Furthermore, the high RVSP at the noted group could present a reliable animal model for POPH in female rats.
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Affiliation(s)
- Ali Sepehrinezhad
- Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amirreza Dehghanian
- Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Rafati
- Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farzaneh Ketabchi
- Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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16
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Shi YJ, Mckiernan P, Soltys K, Mazariegos G, Wang WL. Surgical closure of large splenorenal shunt may accelerate recovery from hepato-pulmonary syndrome in liver transplant patients. World J Emerg Med 2020; 11:60-63. [PMID: 31893005 DOI: 10.5847/wjem.j.1920-8642.2020.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Affiliation(s)
- Yan-Jun Shi
- Department of Hepatobiliary & Pancreas Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.,Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Department of Transplant Surgery, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Patrick Mckiernan
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Department of Transplant Surgery, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Kyle Soltys
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Department of Transplant Surgery, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - George Mazariegos
- Thomas E. Starzl Transplantation Institute, Hillman Center for Pediatric Transplantation, Department of Transplant Surgery, Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Wei-Lin Wang
- Department of Hepatobiliary & Pancreas Surgery, the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
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17
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Alsamri MT, Hamdan MA, Sulaiman M, Narchi H, Souid AK. Hypoxia due to intrapulmonary vascular dilatation in a toddler with a congenital portacaval shunt: case report. BMC Pulm Med 2019; 19:49. [PMID: 30795758 PMCID: PMC6387555 DOI: 10.1186/s12890-019-0788-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Accepted: 01/17/2019] [Indexed: 11/22/2022] Open
Abstract
Background The term hepatopulmonary syndrome typically applies to cyanosis that results from “intrapulmonary vascular dilatation” due to advanced liver disease. Similar findings may result from a congenital portosystemic shunt without liver disease. An adverse consequence of such shunts is intrapulmonary vascular dilatation, which affects the microvascular gas exchange units for oxygen. Case presentation Here, we describe a toddler with chronic cyanosis, exercise intolerance, and finger clubbing due to a malformation shunt between the portal vein and the inferior vena cava. A transcatheter embolization of the shunt resulted in resolution of his findings. Conclusions Congenital portosystemic shunts need to be considered in the differential diagnosis of cyanosis. Electronic supplementary material The online version of this article (10.1186/s12890-019-0788-8) contains supplementary material, which is available to authorized users.
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18
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Surridge A, Atkinson J, Aujayeb A. Platypnoea and orthodeoxia in the hepatopulmonary syndrome. BMJ Case Rep 2019; 12:12/11/e231499. [DOI: 10.1136/bcr-2019-231499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
A 71-year-old female patient with alcohol-induced cirrhosis presented with symptoms of dyspnoea. Previous extensive investigations had detected no apparent cause. Platypnoea and orthodeoxia were observed. A bubble echocardiogram revealed significant intracardiac shunting and a diagnosis of hepatopulmonary syndrome was made. The patient was discharged on home oxygen and referred for liver transplantation.
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19
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Murphy C, Arad D. Case Report: Hepatopulmonary syndrome as the first clinical manifestation of cirrhosis in a patient with underlying chronic lung disease. F1000Res 2019; 7:1175. [PMID: 31354935 PMCID: PMC6635985 DOI: 10.12688/f1000research.15434.2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/08/2019] [Indexed: 11/20/2022] Open
Abstract
An 86 year old woman with multiple chronic lung diseases (including chronic obstructive pulmonary disease, bronchiectasis, and untreated mycobacterium avium-intracellulare) presented with two weeks of increased shortness of breath, notably worse when seated as compared to when lying down. After treatments focused on her known conditions did not resolve her dyspnea, the differential diagnosis was broadened and she was found to have evidence of cirrhosis on imaging. As a result of this new diagnosis, transthoracic echocardiography and arterial blood gas analysis were performed and together yielded the diagnosis of hepatopulmonary syndrome. We describe a rare presentation of hepatopulmonary syndrome manifesting as a patient’s first clinical evidence of suspected cirrhosis, a diagnosis made difficult by this patient’s numerous other lung diseases which muddied the picture.
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Affiliation(s)
- Charles Murphy
- Internal Medicine, Montefiore Medical Center, Bronx, Bronx, NY, 10029, USA
| | - Danit Arad
- Internal Medicine, Montefiore Medical Center, Bronx, Bronx, NY, 10029, USA
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20
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Riou M, Jutant EM, Mignard X, Canuet M, Humbert M, Sitbon O, Savale L, Montani D. Hépatopathies et maladies vasculaires pulmonaires. Rev Med Interne 2018; 39:925-934. [DOI: 10.1016/j.revmed.2018.07.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 07/23/2018] [Indexed: 12/26/2022]
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21
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Fuhrmann V, Krowka M. Hepatopulmonary syndrome. J Hepatol 2018; 69:744-745. [PMID: 29960651 DOI: 10.1016/j.jhep.2018.01.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 12/21/2017] [Accepted: 01/02/2018] [Indexed: 12/04/2022]
Affiliation(s)
- Valentin Fuhrmann
- Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Medicine B, University Hospital Muenster, Muenster, Germany.
| | - Michael Krowka
- Pulmonary and Gastroenterology/Hepatology Division, Mayo Clinic, Rochester, MN, United States
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22
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Tan GP, Abisheganaden JA, Goh SK, Verma A. Reversible platypnoea-orthodeoxia syndrome in post-tuberculosis bronchial stenosis. Respirol Case Rep 2018; 6:e00303. [PMID: 29449947 PMCID: PMC5803928 DOI: 10.1002/rcr2.303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2017] [Revised: 01/07/2018] [Accepted: 01/08/2018] [Indexed: 11/28/2022] Open
Abstract
Bronchial stenosis is known to complicate endobronchial tuberculosis despite medical therapy. It is often associated with dyspnoea. In severe cases, bronchial stenosis results in airflow obstruction, impaired secretion clearance, and can lead to respiratory failure. We present an unusual observation of platypnoea-orthodeoxia syndrome in a young woman with acute atelectasis due to post-tuberculosis bronchial stricture. Imaging revealed complete middle and right lower lobe atelectasis with a partially aerated right upper lobe. In the sitting posture, there was positional worsening of dyspnoea associated with an increase in the alveolar-arterial oxygen gradient and shunt fraction. The likely mechanism was due to gravitational difference in ventilation-perfusion matching. The platypnoea-orthodeoxia syndrome was reversible following balloon dilatation of the bronchial stenosis and expansion of the collapsed lung.
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Affiliation(s)
- Geak Poh Tan
- Department of Respiratory and Critical Care MedicineTan Tock Seng HospitalSingapore
| | | | - Soon Keng Goh
- Department of Respiratory and Critical Care MedicineTan Tock Seng HospitalSingapore
| | - Akash Verma
- Department of Respiratory and Critical Care MedicineTan Tock Seng HospitalSingapore
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23
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Soulaidopoulos S, Cholongitas E, Giannakoulas G, Vlachou M, Goulis I. Review article: Update on current and emergent data on hepatopulmonary syndrome. World J Gastroenterol 2018; 24:1285-1298. [PMID: 29599604 PMCID: PMC5871824 DOI: 10.3748/wjg.v24.i12.1285] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2018] [Revised: 03/01/2018] [Accepted: 03/06/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is a frequent pulmonary complication of end-stage liver disease, characterized by impaired arterial oxygenation induced by intrapulmonary vascular dilatation. Its prevalence ranges from 4% to 47% in patients with cirrhosis due to the different diagnostic criteria applied among different studies. Nitric oxide overproduction and angiogenesis seem to be the hallmarks of a complicated pathogenetic mechanism, leading to intrapulmonary shunting and ventilation-perfusion mismatch. A classification of HPS according to the severity of hypoxemia has been suggested. Contrast-enhanced echocardiography represents the gold standard method for the detection of intrapulmonary vascular dilatations which is required, in combination with an elevated alveolar arterial gradient to set the diagnosis. The only effective treatment which can modify the syndrome’s natural history is liver transplantation. Although it is usually asymptomatic, HPS imparts a high risk of pretransplantation mortality, independently of the severity of liver disease, while there is variable data concerning survival rates after liver transplantation. The potential of myocardial involvement in the setting of HPS has also gained increasing interest in recent research. The aim of this review is to critically approach the existing literature of HPS and emphasize unclear points that remain to be unraveled by future research.
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Affiliation(s)
- Stergios Soulaidopoulos
- Fourth Department of Internal Medicine, Hippokration General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens 11527, Greece
| | - George Giannakoulas
- Department of Cardiology, AHEPA University Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54621, Greece
| | - Maria Vlachou
- Department of Cardiology, AHEPA University Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54621, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
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24
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Rodríguez-Roisin R, Krowka MJ, Agustí A. Hepatopulmonary Disorders: Gas Exchange and Vascular Manifestations in Chronic Liver Disease. Compr Physiol 2018; 8:711-729. [PMID: 29687908 DOI: 10.1002/cphy.c170020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This review concentrates on the determinants of gas exchange abnormalities in liver-induced pulmonary vascular disorders, more specifically in the hepatopulmonary syndrome. Increased alveolar-arterial O2 difference, with or without different levels of arterial hypoxemia, and reduced diffusing capacity represent the most characteristic gas exchange disturbances in the absence of cardiac and pulmonary comorbidities. Pulmonary gas exchange abnormalities in the hepatopulmonary syndrome are unique encompassing all three pulmonary factors determining arterial PO2 , that is, ventilation-perfusion imbalance, increased intrapulmonary shunt and oxygen diffusion limitation that, combined, interplay with two relevant nonpulmonary determinants, that is, increased total ventilation and high cardiac output. Behind the complexity of this lung-liver association there is an abnormal pulmonary vascular tone that combines inhibition of hypoxic pulmonary vasoconstriction with a reduced (or blunted) hypoxic vascular response. The pathology and pathobiology include the presence of intrapulmonary vascular dilatations with or without pulmonary vascular remodeling, i.e. angiogenesis. Liver transplantation, the only effective therapeutic approach to successfully improve and resolve the vast majority of complications induced by the hepatopulmonary syndrome, along with a large list of frustrating pharmacologic interventions, are also reviewed. Another liver-induced pulmonary vascular disorder with less gas exchange involvement, such as portopulmonary hypertension, is also considered. © 2018 American Physiological Society. Compr Physiol 8:711-729, 2018.
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Affiliation(s)
- Robert Rodríguez-Roisin
- Department of Medicine, Universitat de Barcelona (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona
| | - Michael J Krowka
- Division of Pulmonary and Critical Care, Transplant Research Center, Mayo Clinic, Rochester, MN, US
| | - Alvar Agustí
- Service of Pneumology, Respiratory Institute, Hospital Clínic, UB, Centro de Investigaciones Biomédicas en Red sobre Enfermedades Respiratorias (CIBERES), Barcelona
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25
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Ilyas SZ, Tabassum R, Hamed H, Rehman SU, Qadri I. Hepatitis C Virus-Associated Extrahepatic Manifestations in Lung and Heart and Antiviral Therapy-Related Cardiopulmonary Toxicity. Viral Immunol 2017; 30:633-641. [PMID: 28953449 DOI: 10.1089/vim.2017.0009] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Besides liver cirrhosis and hepatocellular carcinoma, chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations (EHMs). HCV exhibits lymphotropism that is responsible for various EHM. An important characteristic of HCV is escape from the immune system, which enables it to produce chronic infections and autoimmune disorders along with accumulation of circulating immune complexes. These EHMs have large spectrum, because they affect many organs such as heart, lungs, kidney, brain, thyroid, and skin. HCV-related cardiac and pulmonary manifestations include myocarditis, cardiomyopathies, cardiovascular diseases (i.e., Stroke, ischemic heart disease), chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, asthma, and interstitial lung diseases. This review discusses etiology and pathogenesis of HCV-associated cardiac and pulmonary manifestations and how different genes, immune system, indirectly linked factors (mixed cryoglobulinemia), liver cirrhosis, and antiviral treatment are involved in HCV-related heart and lung diseases, however, their exact mechanism is not clear.
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Affiliation(s)
- Syeda Zainab Ilyas
- 1 Department of Microbiology and Molecular Genetics, University of the Punjab , Lahore, Pakistan
| | - Rabia Tabassum
- 1 Department of Microbiology and Molecular Genetics, University of the Punjab , Lahore, Pakistan
| | - Haroon Hamed
- 2 Department of Biological Sciences, King Abdul Aziz University , Jeddah, Kingdom of Saudi Arabia
| | - Shafiq Ur Rehman
- 1 Department of Microbiology and Molecular Genetics, University of the Punjab , Lahore, Pakistan
| | - Ishtiaq Qadri
- 2 Department of Biological Sciences, King Abdul Aziz University , Jeddah, Kingdom of Saudi Arabia
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26
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Iqbal S, Smith KA, Khungar V. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Implications for Liver Transplantation. Clin Chest Med 2017; 38:785-795. [PMID: 29128026 DOI: 10.1016/j.ccm.2017.08.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) represent serious pulmonary complications of advanced liver diseases. Orthotopic liver transplantation (OLT) is capable of completely resolving the underlying abnormalities associated with HPS. On the other hand, post-OLT response in patients with PoPH is less predictable, although heavily influenced by pre-OLT mean pulmonary arterial pressure. It remains the case that the opportunity to reverse 2 potentially fatal organ dysfunctions in the liver and the lung make HPS and PoPH more than worthy for further clinical investigations.
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Affiliation(s)
- Shaz Iqbal
- Department of Medicine, General Internal Medicine Division, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
| | - Kerri Akaya Smith
- Department of Medicine, Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 834 West Gates Building, Philadelphia, PA 19104, USA
| | - Vandana Khungar
- Department of Medicine, Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street 2 Dulles, Philadelphia, PA 19104, USA.
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27
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International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation 2017; 100:1440-52. [PMID: 27326810 DOI: 10.1097/tp.0000000000001229] [Citation(s) in RCA: 291] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.
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28
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Abstract
Hepatic function and pulmonary function are interrelated with failure of one organ system affecting the other. With improved therapies, patients with concomitant hepatic and pulmonary failure increasingly enjoy a good quality of life and life expectancy. Therefore, the prevalence of such patients is increasing with more presenting for both emergent and elective surgical procedures. Hypoxemia requires a thorough evaluation in patients with end-stage liver disease. The most common etiologies respond to appropriate therapy. Portopulmonary hypertension and hepatopulmonary syndrome are associated with increased perioperative morbidity and mortality. It is incumbent on the anesthesiologist to understand the physiology of liver failure and its early effect on pulmonary function to ensure a successful outcome.
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29
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Grilo I, Pascasio JM, López-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, Rodríguez-Puras MJ, Ferrer MT, Gómez-Bravo MÁ, Grilo A. Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis? REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS 2017; 109. [DOI: 10.17235/reed.2017.4930/2017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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30
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Abstract
Oxygen is an essential element for life and without oxygen humans can survive for few minutes only. There should be a balance between oxygen demand and delivery in order to maintain homeostasis within the body. The two main organ systems responsible for oxygen delivery in the body and maintaining homeostasis are respiratory and cardiovascular system. Abnormal function of any of these two would lead to the development of hypoxemia and its detrimental consequences. There are various mechanisms of hypoxemia but ventilation/perfusion mismatch is the most common underlying mechanism of hypoxemia. The present review will focus on definition, various causes, mechanisms, and approach of hypoxemia in human.
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Affiliation(s)
- Malay Sarkar
- Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
| | - N Niranjan
- Navodaya Medical College Hospital and Research Center, Raichur, Karnataka, India
| | - P K Banyal
- Community Health Center, Kupvi, Nerwa, Shimla, Himachal Pradesh, India
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31
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Bertino G, Privitera G, Purrello F, Demma S, Crisafulli E, Spadaro L, Koukias N, Tsochatzis EA. Emerging hepatic syndromes: pathophysiology, diagnosis and treatment. Intern Emerg Med 2016; 11:905-16. [PMID: 27273018 DOI: 10.1007/s11739-016-1478-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 05/25/2016] [Indexed: 12/11/2022]
Abstract
Liver cirrhosis is a major cause of morbidity and mortality worldwide, mainly due to complications of portal hypertension. In this article, we review the current understanding on the pathophysiology, the diagnostic criteria and the available therapeutic options for patients with emerging hepatic syndromes in cirrhosis, namely the hepatorenal, hepato-adrenal and hepatopulmonary syndrome. The hepatorenal syndrome is a well-recognized complication of advanced cirrhosis and is usually associated with an accelerated course to death unless liver transplantation is performed. The hepatopulmonary syndrome is often missed in the evaluation of patients with cirrhosis; however, early recognition is essential for the efficient management of individual patients. The hepato-adrenal syndrome, although not fully characterized, offers an exciting field for research and potential therapeutic interventions.
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Affiliation(s)
- Gaetano Bertino
- Hepatology Unit, Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", Catania, Italy
| | - Graziella Privitera
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Catania, Ospedale Garibaldi-Nesima, Catania, Italy
| | - Francesco Purrello
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Catania, Ospedale Garibaldi-Nesima, Catania, Italy
| | - Shirin Demma
- Hepatology Unit, Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", Catania, Italy
| | - Emanuele Crisafulli
- Hepatology Unit, Department of Clinical and Experimental Medicine, University of Catania, Policlinico "G. Rodolico", Catania, Italy
| | - Luisa Spadaro
- Internal Medicine, Department of Clinical and Experimental Medicine, University of Catania, Ospedale Garibaldi-Nesima, Catania, Italy
| | - Nikolaos Koukias
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
| | - Emmanuel A Tsochatzis
- UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK.
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Surani SR, Mendez Y, Anjum H, Varon J. Pulmonary complications of hepatic diseases. World J Gastroenterol 2016; 22:6008-6015. [PMID: 27468192 PMCID: PMC4948262 DOI: 10.3748/wjg.v22.i26.6008] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Revised: 05/01/2016] [Accepted: 05/21/2016] [Indexed: 02/06/2023] Open
Abstract
Severe chronic liver disease (CLD) may result from portal hypertension, hepatocellular failure or the combination of both. Some of these patients may develop pulmonary complications independent from any pulmonary pathology that they may have. Among them the hepatopulmonary syndrome (HPS), portopulmonary hypertension (PPH) and hepatic hydrothorax (HH) are described in detail in this literature review. HPS is encountered in approximately 15% to 30% of the patients and its presence is associated with increase in mortality and also requires liver transplantation in many cases. PPH has been reported among 4%-8% of the patient with CLD who have undergone liver transplantation. The HH is another entity, which has the prevalence rate of 5% to 6% and is associated in the absence of cardiopulmonary disease. These clinical syndromes occur in similar pathophysiologic environments. Most treatment modalities work as temporizing measures. The ultimate treatment of choice is liver transplant. This clinical review provides basic concepts; pathophysiology and clinical presentation that will allow the clinician to better understand these potentially life-threatening complications. This article will review up-to-date information on the pathophysiology, clinical features and the treatment of the pulmonary complications among liver disease patients.
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Grilo-Bensusan I, Pascasio-Acevedo JM. Hepatopulmonary syndrome: What we know and what we would like to know. World J Gastroenterol 2016; 22:5728-5741. [PMID: 27433086 PMCID: PMC4932208 DOI: 10.3748/wjg.v22.i25.5728] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 05/26/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO2) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan (99mTc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.
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Thévenot T, Weil D, Garioud A, Lison H, Cadranel JF, Degano B. [Hepatopulmonary syndrome]. Presse Med 2016; 45:509-14. [PMID: 27021476 DOI: 10.1016/j.lpm.2016.02.017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2015] [Revised: 01/23/2016] [Accepted: 02/08/2016] [Indexed: 12/20/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is defined by the association of portal hypertension, increased alveolar-arterial oxygen gradient and intrapulmonary vascular dilations. Pathophysiological mechanisms of hypoxemia are characterized by ventilation-perfusion mismatch, oxygen diffusion limitation between alveolus and the centre of the dilated capillary, and right-to-left shunting. An excess of vasodilator molecules (like nitric monoxide) and proangiogenic factors (like VEGF) play an important role in the occurrence of HPS. Symptoms of HPS are not specific and dominated by a progressive dyspnea in upright position. Pulse oximetry is a simple non-invasive screening test but only detect the most severe forms of HPS. Medical treatment is disappointing and only liver transplantation may lead to resolution of HPS. Survival following liver transplantation is promising when hypoxemia is not severely decreased.
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Affiliation(s)
- Thierry Thévenot
- Hôpital universitaire Jean-Minjoz, service d'hépatologie et de soins intensifs digestifs, 25030 Besançon, France.
| | - Delphine Weil
- Hôpital universitaire Jean-Minjoz, service d'hépatologie et de soins intensifs digestifs, 25030 Besançon, France
| | - Armand Garioud
- GHPSO - centre hospitalier Laennec, service d'hépato-gastroentérologie et de nutrition, 60109 Creil cedex, France
| | - Hortensia Lison
- GHPSO - centre hospitalier Laennec, service d'hépato-gastroentérologie et de nutrition, 60109 Creil cedex, France
| | - Jean-François Cadranel
- GHPSO - centre hospitalier Laennec, service d'hépato-gastroentérologie et de nutrition, 60109 Creil cedex, France
| | - Bruno Degano
- Hôpital universitaire Jean-Minjoz, service de pneumologie, 25030 Besançon, France
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Cosarderelioglu C, Cosar AM, Gurakar M, Dagher NN, Gurakar A. Hepatopulmonary Syndrome and Liver Transplantation: A Recent Review of the Literature. J Clin Transl Hepatol 2016; 4:47-53. [PMID: 27047772 PMCID: PMC4807143 DOI: 10.14218/jcth.2015.00044] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/10/2016] [Accepted: 02/11/2016] [Indexed: 12/14/2022] Open
Abstract
A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal hypertension, intrapulmonary vascular dilatations, and increased alveolar-arterial oxygen gradient. Prevalence varies according to various study groups from 4%-47%. While the most common presenting symptom of HPS is dyspnea, it is usually asymptomatic, and thus all liver transplant candidates should be screened for its presence. Pulse oximetry is a useful screening method, but arterial blood gas examination is the gold standard. If there is an abnormal P (A-a)O2 gradient, microbubble transthoracic echocardiography should be done for diagnosis. Outcome is unpredictable, and there is currently no effective medical therapy. The only effective therapy is considered to be liver transplantation. Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.
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Affiliation(s)
- Caglar Cosarderelioglu
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
| | - Arif M. Cosar
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
| | - Merve Gurakar
- Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Nabil N. Dagher
- Johns Hopkins University School of Medicine, Department of Surgery/Liver Transplant, Baltimore, MD, USA
| | - Ahmet Gurakar
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
- Correspondence to: Ahmet Gurakar, 720 Rutland Avenue, Ross Research Building, Suite #918, Baltimore, Maryland, 21205, USA, Tel: 410-614-3369, Fax: 410-367-2328, E-mail:
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Rodriguez-Roisin R, Bartolome SD, Huchon G, Krowka MJ. Inflammatory bowel diseases, chronic liver diseases and the lung. Eur Respir J 2016; 47:638-50. [PMID: 26797027 DOI: 10.1183/13993003.00647-2015] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2015] [Accepted: 11/12/2015] [Indexed: 12/12/2022]
Abstract
This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered.
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Affiliation(s)
- Roberto Rodriguez-Roisin
- Servei de Pneumologia (Institut del Tòrax), Hospital Clínic, Institut Biomédic August Pi i Sunyer (IDIBAPS), Ciber Enfermedades Respiratorias (CIBERES), Universitat de Barcelona, Barcelona, Spain
| | - Sonja D Bartolome
- Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, TX, USA
| | - Gérard Huchon
- Service de Pneumologie, Université Paris 5, Paris, France
| | - Michael J Krowka
- Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
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Rathi S, Dhiman RK. Hepatobiliary Quiz (Answers)-16 (2015). J Clin Exp Hepatol 2015; 5:357-60. [PMID: 26900280 PMCID: PMC4723713 DOI: 10.1016/j.jceh.2015.12.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
| | - Radha K. Dhiman
- Address for correspondence: Radha K. Dhiman, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.Department of Hepatology, Postgraduate Institute of Medical Education and ResearchChandigarh160012India
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Goldberg DS, Fallon MB. The Art and Science of Diagnosing and Treating Lung and Heart Disease Secondary to Liver Disease. Clin Gastroenterol Hepatol 2015; 13:2118-27. [PMID: 25934564 PMCID: PMC4618073 DOI: 10.1016/j.cgh.2015.04.024] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Revised: 04/13/2015] [Accepted: 04/14/2015] [Indexed: 02/07/2023]
Abstract
Patients with chronic liver disease are at risk of extrahepatic complications related to cirrhosis and portal hypertension, as well as organ-specific complications of certain liver diseases. These complications can compromise quality of life, while also increasing morbidity and mortality before and after liver transplantation. Patients with chronic liver disease are at risk for pulmonary complications of hepatopulmonary syndrome and portopulmonary syndrome; the cardiac complication fall under the general concept of cirrhotic cardiomyopathy, which can affect systolic and diastolic function, as well as cardiac conduction. In addition, patients with certain diseases are at risk of lung and/or cardiac complications that are specific to the primary disease (ie, emphysema in α-1-antitrypsin deficiency) or occur with increased incidence in certain conditions (ie, ischemic heart disease associated with nonalcoholic steatohepatitis). This article focuses on the epidemiology, clinical presentation, pathogenesis, treatment options, and role of transplantation for lung and heart diseases secondary to liver disease, while also highlighting select liver diseases that directly affect the lungs and heart.
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Affiliation(s)
- David S Goldberg
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Leonard Davis Institute, University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Michael B Fallon
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas
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Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia. Microvascular dilation and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced echocardiography, perfusion lung scanning, and pulmonary arteriography are three currently used diagnostic imaging modalities that identify the presence of intrapulmonary vascular abnormalities. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation. No medical therapy is established as effective for HPS. At the present time, liver transplantation is the only available treatment for HPS.
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Affiliation(s)
- Yong Lv
- Department of Liver Disease, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China,
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40
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Fierro Alanis M, Bastón Rey I, Nieves-Maldonado S, Torre Carballada J, Domínguez-Muñoz J, Ruibal Morell Á. Platypnea-orthodeoxia syndrome: Importance of patient position for correct diagnosis at the time of 99mTc-MAA injection. Rev Esp Med Nucl Imagen Mol 2015. [DOI: 10.1016/j.remnie.2015.05.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Cuadrado A, Díaz A, Iruzubieta P, Salcines JR, Crespo J. Síndrome hepatopulmonar. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 38:398-408. [DOI: 10.1016/j.gastrohep.2015.02.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 02/01/2015] [Accepted: 02/08/2015] [Indexed: 12/17/2022]
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Fierro Alanis MP, Bastón Rey I, Nieves-Maldonado S, Torre Carballada JA, Domínguez-Muñoz JE, Ruibal Morell Á. Platypnea-orthodeoxia syndrome: Importance of patient position for correct diagnosis at the time of (99m)Tc-MAA injection. Rev Esp Med Nucl Imagen Mol 2015; 34:261-3. [PMID: 25881540 DOI: 10.1016/j.remn.2014.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 12/27/2014] [Accepted: 12/31/2014] [Indexed: 11/17/2022]
Abstract
A 65-year-old male presented with unexplained hypoxia that became exacerbated by an upright posture (platypnea-orthodeoxia syndrome) secondary to hepatopulmonary syndrome (HPS). A (99m)Tc-macroaggregated albumin pulmonary perfusion scan revealed a right to left shunt of 29% in the sitting position, which had not been previously detected when the radiotracer injection was performed with the patient in supine position, nor was it diagnosed using another non-invasive imaging method (transthoracic contrast echocardiography and angio-CT). A transesophageal echocardiography was contraindicated due to the presence of esophageal varices. The administration of the radiopharmaceutical in sitting position for the study of the pulmonary perfusion allowed us to confirm the presence of the shunt and consider the patient a candidate for liver transplantation.
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Affiliation(s)
- M P Fierro Alanis
- Departamento Medicina Nuclear, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
| | - I Bastón Rey
- Departamento Gastroenterología, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - S Nieves-Maldonado
- Departamento Medicina Nuclear, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - J A Torre Carballada
- Departamento de Medicina Interna, Complejo Hospitalario Universitario de Santiago, Santiago, Spain
| | - J E Domínguez-Muñoz
- Departamento Gastroenterología, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Á Ruibal Morell
- Departamento Medicina Nuclear, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
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Govindan ML, Kuo KW, Mahani MG, Shanley TP. Refractory hypoxemia caused by hepatopulmonary syndrome: a case report. J Med Case Rep 2014; 8:418. [PMID: 25491238 PMCID: PMC4295258 DOI: 10.1186/1752-1947-8-418] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2014] [Accepted: 10/17/2014] [Indexed: 02/06/2023] Open
Abstract
Introduction Hepatopulmonary syndrome is a clinical syndrome that can affect patients of all ages with liver disease and is more common in children with biliary atresia. Contrast echocardiography is the test of choice to diagnose the presence of intrapulmonary vascular dilatation. The established treatment for hepatopulmonary syndrome is liver transplantation. Case presentation We present the case of an 8-month-old Caucasian baby boy with a history of biliary atresia, polysplenia, and interrupted inferior vena cava who presented with hypoxemia and cyanosis that progressed rapidly. A chest computed tomography angiogram revealed significant dilatation of the pulmonary vasculature, prompting further evaluation and diagnosis of hepatopulmonary syndrome with contrast echocardiography. He was maintained on a milrinone infusion while awaiting liver transplantation. His hypoxemia improved slowly following liver transplantation, requiring tracheostomy and prolonged ventilator dependence. Conclusions Hepatopulmonary syndrome should be included in the differential for progressive hypoxemia in children with liver disease, particularly those with biliary atresia. Imaging with chest computed tomography angiogram and contrast echocardiography should be considered in cases of unexplained refractory hypoxemia.
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Affiliation(s)
- Morgen L Govindan
- Department of Pediatrics and Communicable Diseases, C,S, Mott Children's Hospital, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI, USA.
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Yang W, Hu B, Wu W, Batra S, Blackburn MR, Alcorn JL, Fallon MB, Zhang J. Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS). PLoS One 2014; 9:e113451. [PMID: 25419825 PMCID: PMC4242631 DOI: 10.1371/journal.pone.0113451] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 10/24/2014] [Indexed: 12/18/2022] Open
Abstract
The hepatopulmonary syndrome (HPS) develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2) play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D) which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL). We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064) induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.
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Affiliation(s)
- Wenli Yang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Bingqian Hu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Wei Wu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Sachin Batra
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Michael R. Blackburn
- Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Joseph L. Alcorn
- Division of Neonatology, Department of Pediatrics, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Michael B. Fallon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Junlan Zhang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
- * E-mail:
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45
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Yang Y, Chen B, Chen Y, Zu B, Yi B, Lu K. A comparison of two common bile duct ligation methods to establish hepatopulmonary syndrome animal models. Lab Anim 2014; 49:71-9. [PMID: 25378138 DOI: 10.1177/0023677214558701] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
The major drawback of the current common bile duct ligation (CBDL)-induced hepatopulmonary syndrome (HPS) animal model is the extremely high mortality rate that hinders experimental studies. The purpose of this study was to investigate an improved method of CBDL with the goal of developing a simple and reproducible rat HPS model after a single CBDL treatment. Two groups of male Sprague–Dawley rats underwent separate methods of CBDL: (1) the upper common bile duct ligation (UCBDL) group ( n = 40), in which the first ligature was made near the junction of the hepatic ducts, and the second ligature was made above the entrance of the pancreatic duct; (2) the middle of the common bile duct ligation (MCBDL) group ( n = 40), in which the first ligature was made in the middle of the common bile duct, and the second ligature was made above the entrance of the pancreatic duct. The CBDL-induced HPS rats were evaluated by pulse oximeter, arterial blood analysis, histopathology, and cerebral uptake of intravenous technetium-99m-labeled albumin macroaggregates (which reflects intrapulmonary vascular dilation). The mortality rates of the UCBDL group and the MCBDL group were 42.5% and 77.5%, respectively ( P < 0.05). These results suggest that the UCBDL, a single improved procedure, provides a better method compared to the established HPS model, because of the relatively high success rate and the decreased risk of complications.
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Affiliation(s)
- Y Yang
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
| | - B Chen
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
| | - Y Chen
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
| | - B Zu
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
| | - B Yi
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
| | - K Lu
- Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, PR China
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46
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Mansour AE, Elgamal AA, Zaghlol M. Prevalence and predictors of hepatopulmonary syndrome in liver transplant candidates. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2014. [DOI: 10.1016/j.ejcdt.2014.06.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022] Open
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47
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Aldenkortt F, Aldenkortt M, Caviezel L, Waeber JL, Weber A, Schiffer E. Portopulmonary hypertension and hepatopulmonary syndrome. World J Gastroenterol 2014; 20:8072-8081. [PMID: 25009379 PMCID: PMC4081678 DOI: 10.3748/wjg.v20.i25.8072] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
Portopulmonary hypertension (POPH) and hepatopulmonary syndrome (HPS) are two frequent complications of liver disease, with prevalence among liver transplant candidates of 6% and 10%, respectively. Both conditions result from a lack of hepatic clearance of vasoactive substances produced in the splanchnic territory. Subsequently, these substances cause mainly pulmonary vascular remodeling and some degree of vasoconstriction in POPH with resulting elevated pulmonary pressure and right ventricular dysfunction. In HPS the vasoactive mediators cause intrapulmonary shunts with hypoxemia. Medical treatment is disappointing overall. Whereas liver transplantation (LT) results in the disappearance of HPS within six to twelve months, its effect on POPH is highly unpredictable. Modern strategies in managing HPS and POPH rely on a thorough screening and grading of the disease’s severity, in order to tailor the appropriate therapy and select only the patients who will benefit from LT. The anesthesiologist plays a central role in managing these high-risk patients. Indeed, the important hemodynamic and respiratory modifications of the perioperative period must be avoided through continuation of the preoperatively initiated drugs, appropriate intraoperative monitoring and proper hemodynamic and respiratory therapies.
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48
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Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that induces severe hypoxaemia. Considering the favourable long-term survival of HPS patients as well as the reversal of the syndrome with a functional liver graft, HPS is now an indication for orthotopic liver transplantation (OLT). Consequently, blood gas analysis and imaging techniques should be performed when cirrhotic patients present with shortness of breath as well as when OLT candidates are placed on the transplant waiting list. If the arterial partial pressure of oxygen (PaO2) is more than 10.7 kPa when breathing room air, HPS can be excluded and no other investigation is needed. When the PaO2 when breathing room air is 10.7 kPa or less, contrast-enhanced echocardiography should be performed to exclude pulmonary vascular dilatation. Lung function tests may also help detect additional pulmonary diseases that can contribute to impaired oxygenation. When contrast-enhanced echocardiography is negative, HPS is excluded and no follow-up is needed. When contrast-enhanced echocardiography is positive and PaO2 less than 8 kPa, patients should obtain a severity score that provides them with a reasonable probability of being transplanted within 3 months. In mild-to-moderate HPS (PaO2 8 to 10.6 kPa), periodic follow-up is recommended every 3 months to detect any further deterioration in PaO2. Although no intraoperative deaths have been directly attributed to HPS, oxygenation may worsen immediately following OLT due to volume overload and postoperative infections. Mechanical ventilation is often prolonged with an extended stay in the ICU. A high postoperative mortality (mostly within 6 months) is observed in this group of patients in comparison to non-HPS patients. However, the recovery of an adequate PaO2 within 12 months after OLT explains the similar outcome of HPS and non-HPS patients following OLT over a longer time period.
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Pascasio JM, Grilo I, López-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, Rodriguez-Puras MJ, Ferrer MT, Sayago M, Gómez-Bravo MA, Grilo A. Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation. Am J Transplant 2014; 14:1391-9. [PMID: 24730359 DOI: 10.1111/ajt.12713] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 02/07/2014] [Accepted: 02/10/2014] [Indexed: 01/25/2023]
Abstract
The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen.
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Affiliation(s)
- J M Pascasio
- Digestive Diseases Department, Hospital Virgen del Rocío, Sevilla, Spain
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Abstract
The hepatopulmonary syndrome (HPS) is a pulmonary complication of cirrhosis and/or portal hypertension whereby patients develop hypoxemia as a result of alterations in pulmonary microvascular tone and architecture. HPS occurs in up to 30% of patients with cirrhosis. Although the degree of hypoxemia does not reliably correlate with the severity of liver disease, patients with HPS have a higher mortality than do patients with cirrhosis without the disorder. There has been progress into defining the mechanisms that lead to hypoxemia in HPS, but to date there are no therapeutic options for HPS aside from liver transplantation.
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