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Wu ZP, Wang YF, Shi FW, Cao WH, Sun J, Yang L, Ding FP, Hu CX, Kang WW, Han J, Yang RH, Song QK, Jin JW, Shi HB, Ma YM. Predictive models and clinical manifestations of intrapulmonary vascular dilatation and hepatopulmonary syndrome in patients with cirrhosis: Prospective comparative study. World J Gastroenterol 2025; 31:105720. [PMID: 40309225 PMCID: PMC12038555 DOI: 10.3748/wjg.v31.i15.105720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/13/2025] [Accepted: 03/26/2025] [Indexed: 04/18/2025] Open
Abstract
BACKGROUND Patients with cirrhosis with hepatopulmonary syndrome (HPS) have a poorer prognosis. The disease has a subtle onset, symptoms are easily masked, clinical attention is insufficient, and misdiagnosis rates are high. AIM To compare the clinical characteristics of patients with cirrhosis, cirrhosis combined with intrapulmonary vascular dilatation (IPVD), and HPS, and to establish predictive models for IPVD and HPS. METHODS Patients with cirrhosis were prospectively screened at a liver-specialized university teaching hospital. Clinical information and blood samples were collected, and biomarker levels in blood samples were measured. Patients with cirrhosis were divided into three groups: Those with pure cirrhosis, those with combined IPVD, and those with HPS based on contrast-enhanced transthoracic echocardiography results and the pulmonary alveolar-arterial oxygen gradient values. Univariate logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression methods were utilized to identify risk factors for IPVD and HPS, and nomograms were constructed to predict IPVD and HPS. RESULTS A total of 320 patients were analyzed, with 101 diagnosed with IPVD, of whom 54 were diagnosed with HPS. There were statistically significant differences in clinical parameters among these three groups of patients. Among the tested biomarkers, sphingosine 1 phosphate, angiopoietin-2, and platelet-derived growth factor BB were significantly associated with IPVD and HPS in patients with cirrhosis. Following LASSO logistic regression screening, prediction models for IPVD and HPS were established. The area under the receiver operating characteristic curve for IPVD prediction was 0.792 (95% confidence interval [CI]: 0.737-0.847), and for HPS prediction was 0.891 (95%CI: 0.848-0.934). CONCLUSION This study systematically compared the clinical characteristics of patients with cirrhosis, IPVD, and HPS, and constructed predictive models for IPVD and HPS based on clinical parameters and laboratory indicators. These models showed good predictive value for IPVD and HPS in patients with cirrhosis. They can assist clinicians in the early prognosis assessment of patients with cirrhosis, ultimately benefiting the patients.
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Affiliation(s)
- Zhi-Peng Wu
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Ying-Fei Wang
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Feng-Wei Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Wen-Hui Cao
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Jie Sun
- Department of Respiratory and Critical Care Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Liu Yang
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Fang-Ping Ding
- Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Cai-Xia Hu
- Hepatic Disease and Tumor Interventional Treatment Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Wei-Wei Kang
- Fourth Department of Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Jing Han
- Ultrasound and Functional Diagnosis Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Rong-Hui Yang
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Qing-Kun Song
- Division of Clinical Epidemiology and Evidence-Based Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Jia-Wei Jin
- Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China
| | - Hong-Bo Shi
- Beijing Institute of Hepatology, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
| | - Ying-Min Ma
- Beijing Institute of Hepatology, Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University, Beijing 100069, Beijing, China
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Sidali S, Spaes Y, El Husseini K, Goria O, Mallet V, Poujol-Robert A, Gervais A, Lannes A, Thabut D, Nousbaum JB, Hourmand-Ollivier I, Costentin C, Heurgué A, Houssel-Debry P, Hillaire S, Ganne-Carrié N, Drilhon N, Valainathan SR, Moga L, Tanguy M, Marcault E, Plessier A, Durand F, Raevens S, Paradis V, Cachier A, Elkrief L, Rautou PE. Hepatopulmonary syndrome in patients with porto-sinusoidal vascular disorder: Characteristics and outcome. JHEP Rep 2025; 7:101310. [PMID: 40171298 PMCID: PMC11960633 DOI: 10.1016/j.jhepr.2024.101310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 12/11/2024] [Accepted: 12/16/2024] [Indexed: 04/03/2025] Open
Abstract
Background & Aims Porto-sinusoidal vascular disorder (PSVD) is a rare cause of portal hypertension. Data on hepatopulmonary syndrome (HPS) in PSVD are limited. This study aimed to determine the associated factors, plasma mediators, and evolution of HPS in patients with PSVD. Methods Multicenter observational study of patients with PSVD with signs of portal hypertension in whom contrast-enhanced transthoracic echocardiography (CE-TTE) was performed. Results Among 196 patients with PSVD who underwent CE-TTE in 17 centers, 14 (7% [95% confidence interval 3-11%]) had a confirmed diagnosis of HPS. Patients with HPS more frequently had a genetic disorder associated with PSVD (50% vs. 6%, p <0.001), especially telomere biology disorders (p <0.001). Liver function was less preserved in patients with HPS, because they had lower prothrombin index (63% vs. 86%, p = 0.04), higher serum total bilirubin (37 μmol/L vs. 14 μmol/L, p <0.001), and lower serum albumin (32 g/L vs. 38 g/L, p <0.001). HPS tended to be associated with more portal venule obliterations (p = 0.085) and with nodular liver architecture (p = 0.069). Plasma concentrations of Angiopoietin-2, ICAM3, and Tie2 were higher in patients with HPS (p = 0.02, p = 0.04, p = 0.01, respectively). Out of the 14 patients with HPS, five underwent liver transplantation after a median follow-up of 34 months. Overall cumulative incidence of liver-related events and of death was similar between patients with and without HPS, when considering liver transplantation for HPS as a competing risk. Conclusions HPS in patients with PSVD was associated with genetic disorders, less preserved liver function, and higher plasma concentrations of angiogenic mediators. When applying HPS model for end-stage liver disease exception policy for liver transplantation, overall survival of patients with PSVD and HPS was similar to that of patients with PSVD without HPS. Impact and implications Hepatopulmonary syndrome (HPS) is a rare complication of porto-sinusoidal vascular disorder (PSVD). This multicentric study found that patients with PSVD and HPS had less preserved liver function, and harbored genetic disorders more frequently (especially telomere biology disorders) than patients without HPS. HPS did not negatively impact transplantation-free survival when applying HPS MELD exception policy for liver transplantation through a competitive risk analysis. Our findings suggest that patients with PSVD with respiratory symptoms and/or telomere biology disorders may benefit from systematic screening for HPS.
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Affiliation(s)
- Sabrina Sidali
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Ylang Spaes
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
- Hépato-Gastroentérologie, Centre Hospitalier Universitaire Charles Nicolle, Rouen, France
| | - Kinan El Husseini
- APHP, Service de Pneumologie, Centre de Référence des Maladies Pulmonaires Rares, FHU APOLLO, Hôpital Bichat, Paris, France
| | - Odile Goria
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | | | | | - Anne Gervais
- Hôpital Louis-Mourier, AP-HP, Hépato-gastroentérologie, Paris, France
| | - Adrien Lannes
- Centre Hospitalier Universitaire Angers, Hépatologie, Angers, France
| | - Dominique Thabut
- Service d'Hépato-gastroentérologie, Hôpital Universitaire Pitié-Salpêtrière, AP-HP Sorbonne Université, Paris, France
- Institute of Cardiometabolism and Nutrition, INSERM, Centre de Recherche Saint-Antoine, Sorbonne Université, Paris, France
| | | | | | - Charlotte Costentin
- Hepato-Gastroenterology and Digestive Oncology Department, CHU Grenoble Alpes / Institute for Advanced Biosciences, CNRS UMR 5309-INSERM U1209, University Grenoble Alpes, Grenoble, France
| | - Alexandra Heurgué
- Hépatologie, Centre Hospitalier Universitaire de Reims, Reims, France
| | | | | | - Nathalie Ganne-Carrié
- Liver Unit, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, Assistance Publique Hôpitaux de Paris, Bobigny, France
- Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Sorbonne Paris Nord, Bobigny, France
| | - Nicolas Drilhon
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
| | - Shanta Ram Valainathan
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Lucile Moga
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Marion Tanguy
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
| | - Estelle Marcault
- AP-HP, Hôpital Bichat, Unité de Recherche Clinique Nord Secteur Ouest, Paris, France
| | - Aurélie Plessier
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - François Durand
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University, Ghent University Hospital, Ghent, Belgium
| | - Valérie Paradis
- Département de Pathologie, Hôpital Beaujon, AP-HP Nord, UPC, Clichy, France
| | - Agnès Cachier
- Université Paris-Cité, Department of Cardiology, Bichat/Beaujon Hospital (AP-HP Nord), ENETS Centre of Excellence, Paris, Clichy, France
| | - Laure Elkrief
- Hépato-gastroéntérologie, Hôpital Trousseau, Centre Hospitalier Régional Universitaire, Tours, France
- Faculté de Médecine de Tours, University of Tours, Tours, France
| | - Pierre-Emmanuel Rautou
- Centre de Recherche sur l'Inflammation, Université Paris-Cité, Inserm, Paris, France
- AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France
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Rolim MM, Farsoun LG, Luna CF, Markman-Filho B, Querette P, Lopes EP, Domingues AL. Survival of patients with hepatopulmonary syndrome related to cirrhotic and non-cirrhotic (schistosomiasis) portal hypertension. World J Hepatol 2025; 17:99134. [PMID: 40027571 PMCID: PMC11866160 DOI: 10.4254/wjh.v17.i2.99134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 12/19/2024] [Accepted: 12/25/2024] [Indexed: 02/20/2025] Open
Abstract
BACKGROUND The hepatosplenic schistosomiasis (HSS) with portal hypertension can cause vascular complications such as hepatopulmonary syndrome (HPS). HPS increases the risk of mortality in patients with cirrhosis; however, there is no data on the mortality of patients with HSS and HPS. AIM To perform a survival analysis of patients with HPS related to cirrhotic and non-cirrhotic (schistosomiasis) portal hypertension. METHODS From August 2023 to January 2024, medical records and the official mortality information service of 121 patients who participated in a cross-sectional study on HPS between 2010 and 2012 were analyzed. Survival curves were created using the Kaplan-Meier method, and comparisons were performed using the log-rank test. Cox regression models estimated the hazard ratios (HR). RESULTS Overall, data of 113 patients were analyzed; most (55.8%) had HSS and concomitant cirrhosis (HSS/cirrhosis). Meanwhile, HPS was present in 39 (34.5%) patients. Death occurred in 65 patients [57.5%; 95% confidence interval (CI): 48%-67%. The average time to death was lower in those with HPS when compared to those without HPS (3.37 years vs 5.65 years; P = 0.017). According to the cause of liver disease, patients with HSS/cirrhosis died earlier, and their risk of death was twice as high compared with patients with HSS without cirrhosis (HR: 2.17; 95%CI: 1.3-3.60; P = 0.003). Meanwhile, there were no differences when comparing the two groups with and without HPS (HR: 1.01; 95%CI: 0.59-1.73; P = 0.967). CONCLUSION Patients with HSS and concomitant cirrhosis had a lower survival rate, but there was no difference in survival regardless of the presence of HPS.
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Affiliation(s)
- Melissa M Rolim
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil.
| | - Liana G Farsoun
- Faculdade de Medicina UniNassau, Grupo Ser Educacional, Recife 50100220, Pernambuco, Brazil
| | - Carlos F Luna
- Statistics and Geoprocessing Center, Institute Aggeu Magalhães, Oswaldo Cruz Foundation, Recife 50740465, Pernambuco, Brazil
| | - Brivaldo Markman-Filho
- Department of Cardiology Division, Hospital das Clínicas/EBSERH-Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
- Department of Internal Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
| | - Paulo Querette
- Postgraduate Program in Translational Health, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
| | - Edmundo P Lopes
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
- Department of Internal Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
- Department of Gastroenterology Division, Hospital das Clínicas/EBSERH-Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
| | - Ana L Domingues
- Postgraduate Program in Tropical Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
- Department of Internal Medicine, Center of Medical Sciences, Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
- Department of Gastroenterology Division, Hospital das Clínicas/EBSERH-Universidade Federal de Pernambuco, Recife 50670901, Pernambuco, Brazil
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Zaka AZ, Mangoura SA, Ahmed MA. New updates on hepatopulmonary syndrome: A comprehensive review. Respir Med 2025; 236:107911. [PMID: 39662637 DOI: 10.1016/j.rmed.2024.107911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 11/28/2024] [Accepted: 12/08/2024] [Indexed: 12/13/2024]
Abstract
Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes arterial hypoxemia in the setting of liver disease. HPS has a progressive course and is associated with a two-fold increased risk of mortality relative to cirrhotic patients without HPS. It primarily affects patients with portal hypertension. The key pathological features of HPS include intrapulmonary angiogenesis and vascular dilations (IPVDs). The prevalence of HPS varies widely due to inconsistent diagnostic criteria and a lack of standardized protocols. Despite advances in understanding its pathophysiology, no effective curative treatments for HPS exist. Liver transplantation remains the only definitive treatment, improving survival and altering the disease natural course. This review explores the pathophysiology, clinical features, and therapeutic strategies for HPS, highlighting recent advances in the literature.
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Affiliation(s)
- Andrew Z Zaka
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt.
| | - Safwat A Mangoura
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr, Cairo, 11829, Egypt.
| | - Marwa A Ahmed
- Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt
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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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7
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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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8
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Koc ÖM, Aslan D, Kramer M, Verbeek J, Van Malenstein H, van der Merwe S, Monbaliu D, Vos R, Verleden GM, Pirenne J, Nevens F. Outcomes of liver transplantation for hepatopulmonary syndrome in patients with concomitant respiratory disease. Clin Transplant 2024; 38:e15171. [PMID: 37897208 DOI: 10.1111/ctr.15171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 09/05/2023] [Accepted: 10/17/2023] [Indexed: 10/29/2023]
Abstract
BACKGROUND & AIMS Concomitant respiratory disease is a common finding in patients with hepatopulmonary syndrome (HPS). Among patients who underwent liver transplantation (LT) for HPS, we compared characteristics and outcome of patients with versus without concomitant respiratory disease. METHODS This single center retrospective observational study included patients with HPS who underwent LT between 1999 and 2020. RESULTS During the study period, 32 patients with HPS received a LT; nine (28%) with concomitant respiratory disease of whom one required a combined lung-liver transplantation. Patients with concomitant respiratory disease had higher PaCO2 (38 vs. 33 mm Hg, p = .031). The 30-day postoperative mortality was comparable, but the estimated cumulative probability of resolution of oxygen therapy after LT in HPS patients with versus those without concomitant respiratory disease was lower: 63% versus 91% at 12 months and 63% versus 100% at 18 months (HR 95% CI .140-.995, p = .040). In addition to the presence of concomitant respiratory disease (p = .040), history of smoking (p = .012), and high baseline 99mTcMAA shunt fraction (≥20%) (p = .050) were significantly associated with persistent need of oxygen therapy. The 5-year estimated cumulative probability of mortality in patients with concomitant respiratory disease was worse: 50% versus 23% (HR 95% CI .416-6.867, p = .463). CONCLUSIONS The presence of a concomitant respiratory disease did not increase the short-term postoperative mortality after LT in patients with HPS. However, it resulted in a longer need for oxygen therapy.
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Affiliation(s)
- Özgür M Koc
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
- Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Devrim Aslan
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Matthijs Kramer
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Jef Verbeek
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Hannah Van Malenstein
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Schalk van der Merwe
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Diethard Monbaliu
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Robin Vos
- Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium
| | - Geert M Verleden
- Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium
| | - Jacques Pirenne
- Department of Abdominal Transplantation Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven, Belgium
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9
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Chan SKT, Lim ZMJ, Tay SM. Navigating a complicated liver transplant in a patient with severe hepatopulmonary syndrome without extracorporeal membrane oxygenation: a case report. Singapore Med J 2023; 64:538-542. [PMID: 35082107 PMCID: PMC10476917 DOI: 10.11622/smedj.2022002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 09/28/2021] [Indexed: 11/18/2022]
Affiliation(s)
- Steffi Kang Ting Chan
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
| | | | - Sook Muay Tay
- Division of Anaesthesiology and Perioperative Medicine, Singapore General Hospital, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Duke-NUS Medical School, Singapore
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10
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Raza MH, Kwon Y, Kobierski P, Misra AC, Lim A, Goldbeck C, Etesami K, Kohli R, Emamaullee J. Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease exception policy and outcomes in pediatric patients with hepatopulmonary syndrome requiring liver transplantation. Liver Transpl 2023; 29:134-144. [PMID: 37160070 PMCID: PMC9868062 DOI: 10.1002/lt.26548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 07/11/2022] [Accepted: 07/14/2022] [Indexed: 01/29/2023]
Abstract
Hepatopulmonary syndrome (HPS) is associated with increased waitlist mortality in liver transplantation (LT) candidates. Children with HPS are granted Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) exception points for waitlist prioritization in the United States based on criterion developed for adults. In this study, the impact of this MELD/PELD exception policy on post-LT survival in children was examined. A retrospective cohort of patients aged younger than 18 years with a MELD/PELD exception request who underwent LT between 2007 and 2018 were identified in the Scientific Registry of Transplant Recipients. Patients were stratified by waitlist partial pressure of arterial oxygen (PaO 2 ) to assess risk factors for waitlist mortality and post-LT survival. Among 3082 pediatric LT recipients included in the study, 124 patients (4%) received MELD/PELD exception points for HPS. Patients with HPS were a median age of 9 years (interquartile range: 6, 12 years), 54.8% were girls, and 54% were White. Most patients (87.9%) were listed with laboratory MELD/PELD scores <15. Waitlist mortality for patients with HPS exception points was rare and not different from patients without HPS. When stratified by pre-LT PaO 2 , hypoxemia severity was not associated with differences in 1-, 3-, or 5-year survival rates after LT ( p = 0.13). However, patients with HPS showed a slightly lower survival rate at 5 years compared with patients without HPS (88.7% vs. 93.4%; p = 0.04). MELD/PELD exceptions for children with HPS mitigated waitlist mortality, and recipients with HPS experienced excellent 5-year survival after LT, although slightly lower than in patients without HPS. Unlike adults with HPS, the severity of pre-LT hypoxemia in children does not impact post-LT survival. These data suggest that adult criteria for granting MELD/PELD exception points may not appropriately capture HPS severity in pediatric patients. Further prospective multicenter studies to examine the risk factors predicting negative survival outcomes in children with HPS are warranted.
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Affiliation(s)
- Muhammad H Raza
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Yong Kwon
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Pierre Kobierski
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Asish C Misra
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Angelina Lim
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA
| | - Cameron Goldbeck
- Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA
| | - Kambiz Etesami
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
| | - Rohit Kohli
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA.,Department of Pediatrics , University of Southern California , Los Angeles , California , USA
| | - Juliet Emamaullee
- Keck School of Medicine , University of Southern California , Los Angeles , California , USA.,Division of Hepatobiliary and Abdominal Transplant Surgery, Department of Surgery , University of Southern California , Los Angeles , California , USA.,Liver Transplant Program , Children's Hospital-Los Angeles , Los Angeles , California , USA
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11
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Nascimento ESP, Nunes WMC, Guerra EM, da Roza MR, Silva-Costa S, Machado-Silva W, Avelar GG, de Toledo Nóbrega O, Vieira RP, Amado VM, Melo-Silva CA. Combined exercise training improved exercise capacity and lung inflammation in rats with hepatopulmonary syndrome. Life Sci 2021; 287:120112. [PMID: 34728228 DOI: 10.1016/j.lfs.2021.120112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 10/24/2021] [Accepted: 10/28/2021] [Indexed: 12/15/2022]
Abstract
AIM Physical exercise training attenuates pulmonary inflammation, but its effects on impaired respiratory function caused by hepatopulmonary syndrome (HPS) have not been evaluated. We determined if the combination of moderate intensity aerobic and resistance training during HPS development modifies exercise capacity, respiratory system mechanics, and lung inflammation responses. MAIN METHODS Wistar rats were randomly divided into sham, HPS, and HPS + combined exercise training groups. Fifteen days after HPS induction, a moderate intensity aerobic plus resistance exercise training protocol was performed five times a week for 5 weeks on alternate days. Exercise capacity, respiratory system mechanics, lung inflammation, pulmonary morphology, and immunohistochemistry were evaluated. KEY FINDINGS Overall, our findings indicated that combined exercise training efficiently increased the maximal running and resistance capacity of HPS animals. The training regimen reduced the expression of P2X7 in parenchymal leukocytes (P < 0.01), partially restored the expression of interleukin-10 in airway epithelium (P < 0.01), and increased the expression of TFPI in the airway epithelium (P < 0.01) as well as reduced its expression in parenchymal leukocytes (P < 0.01). However, exercise training did not attenuate HPS-induced respiratory mechanical derangements or lung tissue remodeling. SIGNIFICANCE Combined exercise training can elicit adaptation with regard to both maximal running capacity and maximum strength and modify the expression of P2X7 and TFPI in parenchymal leukocytes and that of IL-10 in airway epithelium.
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Affiliation(s)
| | | | | | | | - Suellen Silva-Costa
- Laboratory of Respiratory Physiology, University of Brasilia, Brasília, DF, Brazil
| | - Wilcelly Machado-Silva
- Graduate Program in Medical Sciences, Medical Faculty, University of Brasilia, Brasília, DF, Brazil
| | - Gleiciane Gontijo Avelar
- Graduate Program in Medical Sciences, Medical Faculty, University of Brasilia, Brasília, DF, Brazil
| | - Otávio de Toledo Nóbrega
- Graduate Program in Medical Sciences, Medical Faculty, University of Brasilia, Brasília, DF, Brazil
| | - Rodolfo P Vieira
- Post-graduation Program in Sciences of Human Movement and Rehabilitation, Federal University of São Paulo, Santos, SP, Brazil; Post-Graduation Program in Bioengineering, Universidade Brasil, São Paulo, SP, Brazil; Brazilian Institute of Teaching and Research in Pulmonary and Exercise Immunology (IBEPIPE), São José dos Campos SP, Brazil
| | - Veronica Moreira Amado
- Laboratory of Respiratory Physiology, University of Brasilia, Brasília, DF, Brazil; Graduate Program in Medical Sciences, Medical Faculty, University of Brasilia, Brasília, DF, Brazil; Division of Pulmonology, University Hospital of Brasilia, Brasília, DF, Brazil
| | - César Augusto Melo-Silva
- Laboratory of Respiratory Physiology, University of Brasilia, Brasília, DF, Brazil; Graduate Program in Medical Sciences, Medical Faculty, University of Brasilia, Brasília, DF, Brazil; Division of Physical Therapy, University Hospital of Brasilia, Brasília, DF, Brazil.
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12
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Hepatopulmonary syndrome delays postoperative recovery and increases pulmonary complications after hepatectomy. Eur J Gastroenterol Hepatol 2021; 33:e449-e457. [PMID: 33852512 DOI: 10.1097/meg.0000000000002134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND This study attempted to investigate the impact of hepatopulmonary syndrome (HPS) on postoperative outcomes in hepatitis B virus-induced hepatocellular carcinoma (HBV-HCC) patients. METHODS HBV-HCC patients undergoing primary curative hepatectomy for HCC in our hospital were diagnosed with HPS by contrast-enhanced echocardiography (CEE) and arterial blood gas analysis. Patients were divided into HPS, intrapulmonary vascular dilation (IPVD) (patients with positive CEE results and normal oxygenation) and control (patients with negative CEE results) groups. Baseline information, perioperative clinical data and postoperative pulmonary complications (PPCs) were compared among all groups. Cytokines in patient serums from each group (n = 8) were also assessed. RESULTS Eighty-seven patients undergoing hepatectomy from October 2019 to January 2020 were analyzed. The average time in the postanaesthesia care unit (112.10 ± 38.57 min) and oxygen absorption after extubation [34.0 (14.5-54.5) min] in the HPS group was longer than in IPVD [81.81 ± 26.18 min and 16.0 (12.3-24.0) min] and control [93.70 ± 34.06 min and 20.5 (13.8-37.0) min] groups. There were no significant differences in oxygen absorption time after extubation between HPS and control groups. The incidence of PPCs, especially bi-lateral pleural effusions in the HPS group (61.9%), was higher than in IPVD (12.5%) and control (30.0%) groups. Increased serum levels of the growth-regulated oncogene, monocyte chemoattractant protein, soluble CD40 ligand and interleukin 8 might be related to delayed recovery in HPS patients. CONCLUSIONS HPS patients with HBV-HCC suffer delayed postoperative recovery and are at higher risk for PPCs, especially bi-lateral pleural effusions, which might be associated with changes in certain cytokines.
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13
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Jose A, Shah SA, Anwar N, Jones CR, McCormack FX, Sherman KE, Elwing JM. Predictors of outcomes following liver transplant in hepatopulmonary syndrome: An OPTN database analysis. Respir Med 2021; 190:106683. [PMID: 34784562 DOI: 10.1016/j.rmed.2021.106683] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/01/2021] [Accepted: 11/08/2021] [Indexed: 02/07/2023]
Abstract
Hepatopulmonary syndrome (HPS) is a type of pulmonary vascular disease occurring exclusively in those with underlying liver disease, associated with significant mortality in patients awaiting liver transplantation (LT). LT is curative in HPS, and these patients are granted Model for End Stage Liver Disease (MELD) exception points to expedite LT. The purpose of this study is to use multivariable competing risk Accelerated Failure Time models and propensity matching to examine the relationship between pre-LT hypoxemia and post-LT outcomes in HPS. We performed a retrospective cohort study of UNOS/OPTN database of all adult patients undergoing LT between January 1, 2006 and January 12, 2020. Pre-LT PaO2 was significantly associated with post-LT mortality in HPS, with each 1 mmHg increase in PaO2 significantly decreasing the risk of post-LT mortality (coefficient 0.039, HR = 0.95, p = 0.001). HPS patients with a pre-LT PaO2 < 54 mmHg demonstrated increased mortality following LT as compared to matched non-HPS cirrhotic patients. We conclude that HPS patients with a PaO2, 54 mmHg are at increased risk of post-LT mortality and may identify high-risk patients who would benefit from additional resources during LT, and that the effects of HPS MELD exception points to optimize post-LT outcomes should be continuously re-evaluated.
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Affiliation(s)
- Arun Jose
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA.
| | - Shimul A Shah
- Department of Surgery, University of Cincinnati, Cincinnati, OH, USA
| | - Nadeem Anwar
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA
| | - Courtney R Jones
- Department of Anesthesiology, University of Cincinnati, Cincinnati, OH, USA
| | - Francis X McCormack
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA
| | - Kenneth E Sherman
- Division of Digestive Diseases, University of Cincinnati, Cincinnati, OH, USA
| | - Jean M Elwing
- Division of Pulmonary, Critical Care, and Sleep Medicine, University of Cincinnati, Cincinnati, OH, USA
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14
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Aragon Pinto C, Iyer VN, Albitar HAH, Anderson A, Cajigas H, Simonetto DA, Krowka MJ, DuBrock HM, Gallo de Moraes A. Outcomes of liver transplantation in patients with hepatopulmonary syndrome in the pre and post-MELD eras: A systematic review. Respir Med Res 2021; 80:100852. [PMID: 34418867 DOI: 10.1016/j.resmer.2021.100852] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 06/15/2021] [Accepted: 07/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND The lack of large hepatopulmonary syndrome cohorts undergoing liver transplantation (LT) has resulted in limited information about post-LT outcomes and expectations. METHODS The long and short-term outcomes of LT in patients with hepatopulmonary syndrome (HPS) were evaluated before and after the implementation of Model for Endstage Liver Disease (MELD) score in 2002, granting exception points for patients with HPS. PubMed/Medline, Embase, Web of Science and Scopus databases were searched for published and unpublished studies from 01/1990 to 04/2019. Studies that included HPS patients who underwent LT and reported post-LT outcomes and HPS severity were reviewed. After reviewing the full text of 1421 articles, 30 were included in the pre-MELD era (before 2002) and 60 in the post-MELD era. RESULTS A total of 598 patients (210 children and 388 adults) with HPS who underwent LT were included in this systematic review. In children, 5-year survival probability was similar in the pre and post-MELD groups (85.7% vs. 97.4; p = 0.09). Median post-transplant PaO2 in room air was higher in the post-MELD group (71 [53-87] vs. 97 [80-108] mmHg: p = 0.008). In adults, 5-year survival probability was higher in the post-MELD era (73 vs. 87.3%; p = 0.008). Median post-transplant PaO2 in room air was higher in post-MELD group (75 [63-85] vs. 87 [75-95] mmHg; p = 0.001).. CONCLUSIONS After MELD exception implementation, survival rates and post-transplant oxygenation improved in adult patients with HPS who underwent liver transplantation, whereas only post-transplant oxygenation improved in children.
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Affiliation(s)
- Catarina Aragon Pinto
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Epidemiology and Translational Research in Intensive Care group (METRIC), Mayo Clinic, Rochester, MN, USA
| | - Vivek N Iyer
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | | | - Alexandra Anderson
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, USA
| | - Hector Cajigas
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - Douglas A Simonetto
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Hilary M DuBrock
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA
| | - Alice Gallo de Moraes
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA; Mayo Epidemiology and Translational Research in Intensive Care group (METRIC), Mayo Clinic, Rochester, MN, USA.
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15
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Soulaidopoulos S, Vlachou M, Cholongitas E, Giannakoulas G, Panagiotidis T, Drakopoulou M, Karvounis H, Goulis I. Assessment of biventricular function in patients with hepatopulmonary syndrome. Int J Cardiovasc Imaging 2021; 37:2891-2900. [PMID: 34114149 DOI: 10.1007/s10554-021-02260-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 04/26/2021] [Indexed: 11/28/2022]
Abstract
Cardiac function impairment in the setting of hepatopulmonary syndrome (HPS) in patients with end stage liver disease remains an issue of debate. The current study evaluated possible correlations between HPS and biventricular systolic function in patients with decompensated cirrhosis. Consecutive liver transplantation candidates with stable decompensated cirrhosis were prospectively evaluated. HPS was defined as the presence of an elevated alveolar-arterial oxygen gradient and intrapulmonary vasodilatation, detected by contrast enhanced echocardiography. HPS severity was determined based on arterial blood oxygen pressure values, while shunt size was assessed with a semi-quantitative method. Demographic, clinical and laboratory parameters were also prospectively collected. In total, 130 patients (mean age 56.5, M/F: 94/36, MELD score 14.6 ± 5.6) were enrolled, of whom 45 (34.6%) fulfilled the criteria for HPS diagnosis (mild: 57.7%, moderate: 33.3%, severe 4.4% and very severe 4.4%). Significantly lower absolute left ventricular (LV) global longitudinal strain (GLS) values (- 21.6 ± 2.3 vs. - 22.6 ± 2.5%, p = 0.041) were measured in patients with HPS compared to cirrhotic patients without HPS, while there was no statistically significant difference regarding right ventricular GLS (- 22.1 ± 3.3 vs. - 23.2 ± 3.5%, p = 0.061) between the two groups. Lower LV ejection fraction values were also recorded in the HPS group (53.9 ± 3.5 vs. 56.3 ± 4.5%, p < 0.01). No other echocardiographic parameter was correlated to HPS. Intrapulmonary shunt grading was correlated to HPS classification (χ2 = 19.8, p < 0.01), with lower arterial oxygen values being recorded in higher stages of intrapulmonary shunt. In patients with cirrhosis, the presence of HPS is associated with worse LV contractile performance.
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Affiliation(s)
- Stergios Soulaidopoulos
- First Cardiology Department, 'Hippokration' General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
- Fourth Department of Internal Medicine, 'Hippokration' General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloníki, Greece.
| | - Maria Vlachou
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, 'Laiko' General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - George Giannakoulas
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - Theofilos Panagiotidis
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - Maria Drakopoulou
- First Cardiology Department, 'Hippokration' General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
| | - Haralambos Karvounis
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloníki, Greece
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, 'Hippokration' General Hospital, Medical School of Aristotle University of Thessaloniki, Thessaloníki, Greece
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16
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Shin S, Suh DI, Ko JM, Park JD, Lee JM, Yi NJ, Kim YT, Park S, Lee S, Koh J, Choi YH. Combined lung and liver transplantation for noncirrhotic portal hypertension with severe hepatopulmonary syndrome in a patient with dyskeratosis congenita. Pediatr Transplant 2021; 25:e13802. [PMID: 32777145 DOI: 10.1111/petr.13802] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 06/10/2020] [Accepted: 07/02/2020] [Indexed: 12/15/2022]
Abstract
DC is caused by defects at the level of telomere maintenance, and cells from patients with this disease have abnormally short telomeres and show premature senescence. One consequence of DC is bone marrow failure. Thus, patients with DC often require HSCT. However, HSCT does not ameliorate other DC-related manifestations. In fact, HSCT can accelerate organ dysfunction due to treatment-related complications, and solid organ transplantation is required in some patients with DC. In this report, we describe the clinical course of a 5-year-old boy who was transferred to our hospital because of progressive dyspnea, 2 years after HSCT. At admission, he had tachypnea and hypoxemia. A liver biopsy was performed for suspected HPS caused by PH, and LT was considered. Eventually, his hypoxemia worsened, and he was transferred to a PICU and started on VA ECMO. He subsequently underwent a CLLT. ECMO was stopped on post-operative day 12, extubation was achieved on post-operative day 29, and the patient recovered well from the surgery. Our results show that CLLT could be a life-saving treatment option for DC patients with very severe HPS in whom a poor outcome is expected after LT.
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Affiliation(s)
- Sohyun Shin
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Dong In Suh
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Jung Min Ko
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - June Dong Park
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - Young Tae Kim
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Korea
| | - Samina Park
- Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Korea
| | - Seunghyun Lee
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jaemoon Koh
- Department of Pathology, Seoul National University Hospital, Seoul, Korea
| | - Yu Hyeon Choi
- Department of Pediatrics, Seoul National University Hospital, Seoul, Korea
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17
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Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension. Acta Gastroenterol Belg 2021; 84:95-99. [PMID: 33639700 DOI: 10.51821/84.1.200] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Liver disease, cirrhosis and portal hypertension can be complicated by pulmonary vascular disease, which may affect prognosis and influence liver transplantation (LT) candidacy. Pulmonary vascular complications comprise hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). Although these two conditions develop on a same background and share a common trigger, pulmonary responses are distinct and occur at different anatomical sites of the pulmonary circulation. HPS affects 10-30% of patients referred for LT, and is characterized by gas exchange abnormalities due to pulmonary vasodilation and right-to-left shunting. POPH occurs in 5%, and is defined by pulmonary arterial hypertension due to increased pulmonary vascular resistance, which leads to hemodynamic failure. Even though HPS and POPH may have a substantial negative impact on survival, both entities are clinically underrecognized and frequently misdiagnosed. Without intervention, the 5-year survival rate is 23% in HPS and 14% in POPH. Their presence should be actively sought by organized screening in patients presenting with dyspnea and in all patients on the waitlist for LT, also because clinical symptoms are commonly non-specific or even absent. LT may lead to resolution, however, advanced stages of either HPS or POPH may jeopardize safe and successful LT. This implicates the need of proper identification of HPS and POPH cases, as well as the need to be able to successfully 'bridge' patients to LT by medical intervention. A review article on this topic has been published in this journal in 2007 (1). This updated review focuses on recent advances in the diagnosis and management of these 2 liver-induced pulmonary vascular disorders and incorporates results from our recent work.
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18
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Raghunathan V, Mohan N, Dhaliwal M, Bhangui P, Vohra V, Soin AS. Pediatric liver transplantation in severe hepatopulmonary syndrome and use of inhaled nitric oxide for post-transplant hypoxemia-a single center experience. Pediatr Transplant 2020; 24:e13792. [PMID: 32881212 DOI: 10.1111/petr.13792] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Revised: 06/13/2020] [Accepted: 06/22/2020] [Indexed: 02/06/2023]
Abstract
Data on pediatric patients with HPS undergoing LT are limited. Our aim was to study the spectrum and outcomes of pediatric patients with HPS undergoing LDLT. The role ofiNO for post-LDLT refractory hypoxemia was also assessed. Patients (aged < 18 years) undergoing LT were retrospectively studied. HPS was diagnosed based on European Respiratory Society Taskforce 2004 criteria. HPS was graded based on oxygenation criteria and contrast-enhanced echocardiogram. Post-operative course was studied. Refractory post-operative hypoxemia was treated with iNO by institutionally developed protocol. 23/150 pediatric patients undergoing LDLT had HPS. BA was the most common underlying cause (52.2%). By oxygenation criteria, 6 (26.1%) had VS-HPS. VS-HPS was associated with longer LOS (p = .031) and prolonged oxygen requirement (p = .001) compared with other HPS patients. 4/6 patients with VS-HPS had pO2 < 45 mm Hg. Among these, 2 developed ICH post-operatively and 1 died. 3 developed refractory post-operative hypoxemia, successfully treated with iNO. Mean duration of iNO was 26.3 days. In the group of patients with HPS, the incidence of HAT and portal vein thrombosis was 17.3% and 4.3%, respectively. One year post-LDLT survival of patients with HPS was similar to non-HPS patients (86.9% vs 94.4%; p = .88). We concluded that, pediatric patients with VS-HPS, especially those with pre-operative pO2 < 45 mm Hg, have long and difficult post-LT course. Refractory postoperative hypoxemia can be successfully overcome with strategic use of iNO. Vigilant monitoring and good intensive care support are essential.
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Affiliation(s)
- Veena Raghunathan
- Department of Pediatric Critical Care, Medanta The Medicity, Gurgaon, India
| | - Neelam Mohan
- Department of Pediatric Gastroenterology, Hepatology & Liver Transplant, Medanta The Medicity, Gurgaon, India
| | - Maninder Dhaliwal
- Department of Pediatric Critical Care, Medanta The Medicity, Gurgaon, India
| | - Prashant Bhangui
- Institute of Liver Transplant & Regenerative Medicine, Medanta The Medicity, Gurgaon, India
| | - Vijay Vohra
- Institute of Liver Transplant & Regenerative Medicine, Medanta The Medicity, Gurgaon, India
| | - Arvinder Singh Soin
- Institute of Liver Transplant & Regenerative Medicine, Medanta The Medicity, Gurgaon, India
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19
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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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20
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Weinfurtner K, Forde K. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Current Status and Implications for Liver Transplantation. CURRENT HEPATOLOGY REPORTS 2020; 19:174-185. [PMID: 32905452 PMCID: PMC7473417 DOI: 10.1007/s11901-020-00532-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
PURPOSE OF REVIEW Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are both pulmonary vascular complications of advanced liver disease; however, these syndromes have distinct pathophysiology, clinical implications, and management. RECENT FINDINGS While both conditions are associated with portal hypertension, HPS results from diffuse pulmonary capillary vasodilation and PoPH results from vasoconstriction and vascular remodeling of pulmonary arteries. In HPS, no medical therapies clearly improve outcomes; however, patients have excellent post-LT outcomes with near uniform reversal of hypoxemia. In PoPH, several medical therapies used in idiopathic pulmonary hypertension have been shown improve pulmonary hemodynamics, symptoms, and potentially LT outcomes; however, further study is needed to determine best treatment regimens, long-term outcomes on medical therapy, and role of LT. SUMMARY While HPS results in severe hypoxemia that is usually reversible by LT, PoPH patients develop progressive pulmonary hypertension that may improve with medical therapy.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kimberly Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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21
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Comparison of Two Diagnostic Criteria for Hepatopulmonary Syndrome-High Prevalence in Biliary Atresia. J Pediatr Gastroenterol Nutr 2020; 70:623-627. [PMID: 31939865 DOI: 10.1097/mpg.0000000000002621] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES There is lack of clarity regarding the exact prevalence of hepatopulmonary syndrome (HPS) in pediatric liver diseases owing to lack of standardized diagnostic criteria. Thus, we aimed to do a comparative study of HPS with respect to its prevalence using the available diagnostic criteria. METHODS All consecutive children with biliary atresia (BA) and other chronic liver diseases (CLDs) were studied. Prevalence of HPS was compared using the 2 available criteria: demonstration of intrapulmonary vascular dilatation along with either alveolar-arterial oxygen difference (P [A-a] O2) on arterial blood gas analysis of more than 15 mmHg (criteria 1), or higher than age-appropriate calculated value for P (A-a) O2 (criteria 2). RESULTS A total of 42 children in BA group and 62 in the non-BA CLD group were included. Using the criteria 1, the prevalence of HPS was 42.3%: 57.1% in the BA group and 32.2% in the CLD group, whereas using criteria 2, the prevalence was 48.1%: 61.9% in the BA group and 38.7% in the CLD group. Criteria 2 diagnosed 6 additional patients with HPS compared to criteria 1 (P value 0.405). BA subjects had higher risk (2.9-3 folds) of developing HPS compared to other CLDs. CONCLUSION There is high prevalence of HPS in pediatric liver disease subjects. Age-appropriate formula for HPS diagnosis may be better applicable in pediatric population. BA subjects have a higher risk of developing HPS compared to other CLDs overall, irrespective of the severity of liver disease and/or portal hypertension.
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22
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Resources Utilization After Liver Transplantation in Patients With and Without Hepatopulmonary Syndrome: Cleveland Clinic Experience. Transplant Direct 2020; 6:e545. [PMID: 32309631 PMCID: PMC7145001 DOI: 10.1097/txd.0000000000000990] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2019] [Revised: 01/30/2020] [Accepted: 02/21/2020] [Indexed: 11/25/2022] Open
Abstract
Patients with hepatopulmonary syndrome (HPS) reportedly experience posttransplant morbidity and require more resources to care during perioperative period. The exact incremental increase of resources utilization compared with non-HPS population remains unknown.
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23
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Soulaidopoulos S, Goulis I, Cholongitas E. Pulmonary manifestations of chronic liver disease: a comprehensive review. Ann Gastroenterol 2020; 33:237-249. [PMID: 32382226 PMCID: PMC7196609 DOI: 10.20524/aog.2020.0474] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2019] [Accepted: 12/06/2019] [Indexed: 12/14/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) and porto-pulmonary hypertension (PoPH) represent relatively common pulmonary vascular complications of advanced liver disease. Despite distinct differences in their pathogenetic background, both clinical states are characterized by impaired arterial oxygenation and limited functional status, and are associated with increased pre-transplantation mortality. Accumulation of ascitic fluid in the pleural cavity, known as hepatic hydrothorax (HH), is another frequent manifestation of decompensated cirrhosis, which may cause severe respiratory dysfunction, depending on the volume of the effusion, the rapidity of its development and its resistance to therapeutic measures. Orthotopic liver transplantation constitutes the only effective treatment able to resolve the pulmonary complications of liver disease. A prioritization policy for liver transplantation has evolved over the past years regarding advanced stages of HPS, yielding favorable outcomes regarding post-transplantation survival and HPS resolution. In contrast, severe PoPH is associated with poor post-transplantation survival. Hence, liver transplantation is recommended only for patients with PoPH and an acceptable reduction in pulmonary pressure values, after receiving PoPH-targeted vasodilating therapy. This review focuses on basic pathogenetic and diagnostic principles and discusses the current therapeutic approaches regarding HPS, PoPH, and HH.
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Affiliation(s)
- Stergios Soulaidopoulos
- First Department of Cardiology, Hippokration General Hospital, National and Kapodistrian University of Athens (Stergios Soulaidopoulos)
| | - Ioannis Goulis
- Fourth Department of Internal Medicine, Hippokration General Hospital, Medical School of Aristotle University of Thessaloniki (Ioannis Goulis)
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens (Evangelos Cholongitas), Greece
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24
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Jin X, Sun BJ, Song JK, Roh JH, Jang JY, Kim DH, Lim YS, Song JM, Kang DH, Lee SG. Time-dependent reversal of significant intrapulmonary shunt after liver transplantation. Korean J Intern Med 2019; 34:510-518. [PMID: 29502364 PMCID: PMC6506742 DOI: 10.3904/kjim.2017.152] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 09/18/2017] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND/AIMS Although the association between intrapulmonary shunt (IPS) and liver cirrhosis is clear, data of repeated contrast echocardiography (CE) before and after liver transplantation (LT) to evaluate factors associated with IPS are limited. METHODS Hand-agitated saline was used for CE and, by assessing left-chamber opacification, IPS was classified as grade 0 to 4. Grade 3/4 constituted significant IPS and hepatopulmonary syndrome (HPS) was defined as significant IPS with the arterial partial pressure of oxygen < 70 mmHg. RESULTS Before LT, 253 patients underwent CE and the frequency of significant IPS and HPS were 44% (n = 112) and 7% (n = 17), respectively. Child-Pugh score (odds ratio [OR], 1.345; 95% confidence interval [CI], 1.090 to 1.660; p = 0.006) and arterial oxygen content (OR, 0.838; 95% CI, 0.708 to 0.991; p = 0.039) were independent determinants of significant IPS, whereas direct bilirubin (OR, 1.076; 95% CI, 1.012 to 1.144; p = 0.019) was the only variable associated with HPS. Among 153 patients who underwent successful LT, repeated CE was performed in 97 (63%), which showed significant reductions in IPS grade (from 2.6 ± 1.0 to 1.2 ± 1.3, p < 0.001) and the prevalence of significant IPS (from 56% to 20%, p = 0.038). After adjustment for pre-LT IPS grade, time from LT to repeated CE presented negative linear relationship with post-LT IPS grade (r 2 = 0.366, p < 0.001) and was the only determinant of post-LT IPS grade (OR, 1.009; 95% CI, 1.003 to 1.014; p = 0.004). CONCLUSION Repeated CE is useful to evaluate intrapulmonary vascular change before and after LT. Reversal of IPS after successful LT is time-dependent and follow-up duration should be considered for accurate assessment of IPS after LT.
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Affiliation(s)
- Xin Jin
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Byung Joo Sun
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae-Kwan Song
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- Correspondence to Jae-Kwan Song, M.D. Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea Tel: +82-2- 3010-3155 Fax: +82-2-486-5918 E-mail:
| | - Jae-Hyung Roh
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jeong Yoon Jang
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Dae-Hee Kim
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jong-Min Song
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Duk-Hyun Kang
- Cardiac Imaging Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Sung Gyu Lee
- Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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25
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Lejealle C, Paradis V, Bruno O, de Raucourt E, Francoz C, Soubrane O, Lebrec D, Bedossa P, Valla D, Mal H, Vilgrain V, Durand F, Rautou PE. Evidence for an Association Between Intrahepatic Vascular Changes and the Development of Hepatopulmonary Syndrome. Chest 2019; 155:123-136. [DOI: 10.1016/j.chest.2018.09.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Revised: 08/21/2018] [Accepted: 09/05/2018] [Indexed: 02/06/2023] Open
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26
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Perioperative Management of Patients with Hepatopulmonary Syndrome. CURRENT TRANSPLANTATION REPORTS 2018. [DOI: 10.1007/s40472-018-0208-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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27
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Liu JW, Chen DQ. Correlations of MMP-2 and MMP-9 gene polymorphisms with the risk of hepatopulmonary syndrome in cirrhotic patients: A case-control study. Kaohsiung J Med Sci 2018; 34:634-642. [DOI: 10.1016/j.kjms.2018.06.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 03/21/2018] [Accepted: 06/14/2018] [Indexed: 12/17/2022] Open
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Screening for Hepatopulmonary Syndrome in Cirrhotic Patients Using Technetium 99m-macroaggregated Albumin Perfusion Lung Scan (Tc-MAA): Diagnostic Approach and Clinical Correlations. J Clin Gastroenterol 2018; 52:828-834. [PMID: 28961571 DOI: 10.1097/mcg.0000000000000926] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The aims of this study were to prospectively screen cirrhotic patients with arterial blood gas test and albumin perfusion scan, identify those fulfilling the classic hepatopulmonary syndrome (HPS) criteria, correlate with clinical parameters, and evaluate the survival of patients with HPS compared with those without HPS in a genetically homogenous Cretan cirrhotic population. MATERIALS AND METHODS Data on consecutive 102 patients within 1 year were collected and analyzed. All patients underwent a technetium 99m-macroaggregated albumin perfusion lung scan (Tc-MAA). Diagnosis of HPS was based on the presence of the quantitative index Tc-MAA≥6% and a [P(A-a)O2]≥15 mm Hg (≥20 mm Hg for patients over >64 y). RESULTS In 94/102 patients, complete scintigraphic data were available. In total, 24 (26%) patients fulfilled the diagnostic criteria of HPS; 95.8% of them had mild-to-moderate HPS. In 8 patients the Tc-MAA scintigraphy could not be interpreted. There was no difference in HPS between decompensated (24.6%) and compensated cirrhosis (27.3%). In the multivariate analysis only the quantitative index was significant for the diagnosis of HPS (P=0.001, odds ratio; 95% confidence interval, 7.05; 2.27-21.87). Kaplan- Meier survival curves indicated a similar overall prognosis for patients diagnosed with HPS (P=0.105). CONCLUSIONS HPS is a frequent complication of cirrhosis. Mild-to-moderate HPS has no significant effect on survival of cirrhotic patients. The quantitative Tc-MAA test is a reliable tool for diagnosis.
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29
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Cardoso FS, Karvellas CJ. Respiratory Complications Before and After Liver Transplant. J Intensive Care Med 2018; 34:355-363. [PMID: 29886790 DOI: 10.1177/0885066618781526] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Respiratory complications before and after liver transplant are common, diverse, and potentially have a negative impact on patient outcomes. In this review, we discuss the most frequent respiratory conditions that patients may develop in the perioperative period. Their prevention and/or treatment may help to maximize the benefit these patients may derive from liver transplant. This review examines diagnostic and therapeutic approaches to these complications for hepatologists, surgeons, and critical care physicians.
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Affiliation(s)
- Filipe S Cardoso
- 1 Gastroenterology and Intensive Care Divisions, Hospital Curry Cabral, Central Lisbon Hospital Center, Nova Medical School, Nova University, Lisbon, Portugal
| | - Constantine J Karvellas
- 2 Division of Gastroenterology (Liver Unit) and Department of Critical Care Medicine, University of Alberta, Edmonton, Canada
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30
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Vetrugno L, Barnariol F, Bignami E, Centonze GD, De Flaviis A, Piccioni F, Auci E, Bove T. Transesophageal ultrasonography during orthotopic liver transplantation: Show me more. Echocardiography 2018; 35:1204-1215. [PMID: 29858886 DOI: 10.1111/echo.14037] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The first perioperative transesophageal echocardiography (TEE) guidelines published 21 years ago were mainly addressed to cardiac anesthesiologists. TEE has since expanded its role outside this setting and currently represents an invaluable tool to assess chamber sizes, ventricular hypertrophy, and systolic, diastolic, and valvular function in patients undergoing orthotopic liver transplantation (OLT). Right-sided microemboli, right ventricular dysfunction, and patent foramen ovale (PFO) are the most common intra-operative findings described during OLT. However, left ventricular outflow tract obstruction and left ventricular ballooning syndrome are more difficult to recognize and less frequent. Transesophageal ultrasonography (TEU) during OLT is also underused. Its applications are as follows: (1) assistance in the difficult placement of pulmonary arterial catheters; (2) help with catheterization of great vessels for external veno-venous bypass placement; (3) intra-operative evaluation of surgical liver anastomosis patency, if feasible, through the liver window; and (4) intra-operative investigation of "acute hypoxemia" due to pulmonary and cardiac issues using trans-esophageal lung ultrasound (TELU). The aims of this review are as follows: (1) to summarize the uses of TEE and TEU throughout all phases of OLT, and (2) to describe other new feasible applications.
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Affiliation(s)
- Luigi Vetrugno
- Anesthesiology and Intensive Care Clinic, Department of Medicine, University of Udine, Udine, Italy
| | - Federico Barnariol
- Anesthesiology and Intensive Care 1, Department of Anesthesia and Intensive Care Medicine, University-Hospital of Udine, Udine, Italy
| | - Elena Bignami
- Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Parma, Italy
| | - Grazia D Centonze
- Anesthesiology and Intensive Care Clinic, Department of Medicine, University of Udine, Udine, Italy
| | - Adelisa De Flaviis
- Anesthesiology and Intensive Care Clinic, Department of Medicine, University of Udine, Udine, Italy
| | - Federico Piccioni
- Department of Critical Care Medicine and Support Therapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Elisabetta Auci
- Anesthesiology and Intensive Care 2, Department of Anesthesia and Intensive Care Medicine, University-Hospital of Udine, Udine, Italy
| | - Tiziana Bove
- Anesthesiology and Intensive Care Clinic, Department of Medicine, University of Udine, Udine, Italy
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31
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Herborn J, Lewis C, De Wolf A. Liver Transplantation: Perioperative Care and Update on Intraoperative Management. CURRENT ANESTHESIOLOGY REPORTS 2018. [DOI: 10.1007/s40140-018-0270-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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32
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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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33
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Khan HH, Schroeder L, Fitzpatrick MS, Kaufman SS, Yazigi NA, Yurasek GK, Steinhorn DM, Fishbein TM, Khan KM. Successful venoarterial extracorporeal membrane oxygenation for prolonged hepatopulmonary syndrome following pediatric liver transplantation: A case report and review of the literature. Pediatr Transplant 2017; 21. [PMID: 28833992 DOI: 10.1111/petr.13036] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/27/2017] [Indexed: 01/16/2023]
Abstract
HPS is a major complicating feature of end-stage liver disease. Diagnosis is clinical, and LT is the only definitive treatment. While the general impression is that HPS improves quickly after transplantation, it may not always be the case. We describe the smallest reported child with HPS prior to LT and requiring prolonged venoarterial extracorporeal membrane oxygenation after LT; especially as it is a rare occurrence, physician managing such cases should be aware of the circumstances under which HPS may require specific treatment.
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Affiliation(s)
- Hamza Hassan Khan
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Laura Schroeder
- Critical Care Medicine, Childrens National Medical Center, Washington, DC, USA
| | - Megha S Fitzpatrick
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Stuart S Kaufman
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Nada A Yazigi
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Gregory K Yurasek
- Critical Care Medicine, Childrens National Medical Center, Washington, DC, USA
| | - David M Steinhorn
- Critical Care Medicine, Childrens National Medical Center, Washington, DC, USA
| | - Thomas M Fishbein
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
| | - Khalid M Khan
- Transplant Institute, Medstar Georgetown University Hospital, Washington, DC, USA
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34
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Tonelli AR, Naal T, Dakkak W, Park MM, Dweik RA, Stoller JK. Assessing the kinetics of microbubble appearance in cirrhotic patients using transthoracic saline contrast-enhanced echocardiography. Echocardiography 2017; 34:1439-1446. [PMID: 28840954 DOI: 10.1111/echo.13662] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The number of cardiac cycles that need to be reviewed by echocardiography before a significant intrapulmonary shunt can be excluded remains unclear. METHODS We retrospectively identified patients with cirrhosis who underwent technetium-99 m-labeled macroaggregated albumin scanning. The kinetics of bubble appearance after the injection of agitated saline during transthoracic echocardiograms were assessed in these patients. RESULTS For the 64 eligible patients, the mean ± SD age was 56 ± 9 years. The median (IQR) shunt fraction by radionuclide scanning was 7.7% (2.8%-19.9%). Microbubbles were seen in the left atrium (LA) and left ventricle (LV) at a median (IQR) of 4 (2-5) and 4 (2-5) beats, respectively. The number of heart cycles before microbubbles appeared in the LA or LV was inversely associated with the nuclear scanning shunt fraction (R = -0.42, P = .001, R = -0.46, P < .001, respectively). If no microbubbles were detected by heart cycle 7, the shunt fraction was uniformly less than 3%. Patients with arterial oxygen <60 mm Hg, compared to ≥60 mm Hg, had earlier appearance of microbubbles in the left heart chambers (2.6 ± 1.9 vs 4.0 ± 2.3 beats, P = .046). CONCLUSIONS In patients with advanced cirrhosis suspected of having hepatopulmonary syndrome, a greater shunt fraction during nuclear scanning was associated with more pronounced hypoxemia and a prompt and more intense appearance of microbubbles in the left-sided heart chambers. Patients with a shunt fraction above 3% have microbubbles in the LA or LV at some point during the first seven heart cycles.
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Affiliation(s)
- Adriano R Tonelli
- Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Tawfeq Naal
- Pathobiology Department, Cleveland Clinic, Cleveland, OH, USA
| | - Wael Dakkak
- Department of Internal Medicine, John H. Stroger Jr. Hospital of Cook County, Chicago, IL, USA
| | - Margaret M Park
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Raed A Dweik
- Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Cleveland Clinic, Cleveland, OH, USA
| | - James K Stoller
- Department of Pulmonary, Allergy and Critical Care Medicine, Respiratory Institute, Education Institute, Cleveland Clinic, Cleveland, OH, USA
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Mendizabal M, Goldberg D, Piñero F, Arufe D, José de la Fuente M, Testa P, Coronel M, Baratta S, Podestá L, Fallon M, Silva M. Isolated Intrapulmonary Vascular Dilatations and the Risk of Developing Hepatopulmonary Syndrome in Liver Transplant Candidates. Ann Hepatol 2017; 16:548-554. [PMID: 28611257 DOI: 10.5604/01.3001.0010.0289] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series. AIMS To assess the development of hepatopulmonary síndrome (HPS) in patients with isolated IPVD and to evaluate outcomes of IPVD and HPS among patients evaluated for liver transplantation (LT). MATERIAL AND METHODS Data from a prospective cohort of patients evaluated for LT with standardized screening for HPS were analyzed. IPVDs were defined as the presence of microbubbles in the left atrium > 3 cycles following right atrial opacification. HPS was defined as the presence of IPVD and hypoxemia (Alveolar-arterial gradient ≥ 15 mmHg) in the absence of concomitant cardiopulmonary disease. RESULTS A total of 104 patients with negative contrast-enhanced echocardiogram (CE) were compared to 63 patients with IPVD and 63 patients with HPS. Only four patients were categorized as ‘severe’ HPS based on degree of hipoxemia (defined as PaO2 < 60 mmHg). Twenty IPVD patients were followed with ABG over a mean duration of 21 months (range 9-43), of whom 7 (35%) subsequently met HPS criteria. Overall unadjusted survival from the time of LT evaluation using multi-state survival models that accounted for pre- and post-LT time was not statistically different among the three groups (negative CE, IPVD, and HPS; p > 0.5). CONCLUSIONS Patients with IPVD appear to have a substantial risk of developing oxygenation impairment over time and progress to HPS. In our cohort, survival in patients with HPS and isolated IPVD is not different when compared to those without IPVDs.
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Affiliation(s)
- Manuel Mendizabal
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - David Goldberg
- Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Federico Piñero
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Diego Arufe
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - María José de la Fuente
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Pablo Testa
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Matías Coronel
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Sergio Baratta
- Cardiology Institute, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Luis Podestá
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
| | - Michael Fallon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA
| | - Marcelo Silva
- Hepatology and Liver Transplant Unit, Hospital Universitario Austral, Pilar, Buenos Aires, Argentina
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International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation 2017; 100:1440-52. [PMID: 27326810 DOI: 10.1097/tp.0000000000001229] [Citation(s) in RCA: 286] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Two distinct pulmonary vascular disorders, hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) may occur as a consequence of hepatic parenchymal or vascular abnormalities. HPS and POPH have major clinical implications for liver transplantation. A European Respiratory Society Task Force on Pulmonary-Hepatic Disorders convened in 2002 to standardize the diagnosis and guide management of these disorders. These International Liver Transplant Society diagnostic and management guidelines are based on that task force consensus and should continue to evolve as clinical experience dictates. Based on a review of over 1000 published HPS and POPH articles identified via a MEDLINE search (1985-2015), clinical guidelines were based on, selected single care reports, small series, registries, databases, and expert opinion. The paucity of randomized, controlled trials in either of these disorders was noted. Guidelines are presented in 5 parts; I. Definitions/Diagnostic criteria; II. Hepatopulmonary syndrome; III. Portopulmonary hypertension; IV. Implications for liver transplantation; and V. Suggestions for future clinical research.
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Grilo I, Pascasio JM, Tirado JL, López-Pardo FJ, Ortega-Ruiz F, Sousa JM, Rodríguez-Puras MJ, Ferrer MT, Gómez-Bravo MÁ, Grilo Reina A. The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:335-343. [PMID: 28301945 DOI: 10.17235/reed.2017.4219/2016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The macro-aggregated albumin lung perfusion scan (99mTc-MAA) is a diagnostic method for hepatopulmonary syndrome (HPS). GOAL To determine the sensitivity of 99mTc-MAA in diagnosing HPS, to establish the utility of 99mTc-MAA in determining the influence of HPS on hypoxemia in patients with concomitant pulmonary disease and to determine the correlation between 99mTc-MAA values and other respiratory parameters. METHODS Data from 115 cirrhotic patients who were eligible for liver transplantation (LT) were prospectively analyzed. A transthoracic contrast echocardiography and 99mTc-MAA were performed in 85 patients, and 74 patients were diagnosed with HPS. RESULTS The overall sensitivity of 99mTc-MAA for the diagnosis of HPS was 18.9% (14/74) in all of the HPS cases and 66.7% (4/6) in the severe to very severe cases. In HPS patients who did not have lung disease, the degree of brain uptake of 99mTc-MAA was correlated with the alveolar-arterial oxygen gradient (A-a PO2) (r = 0.32, p < 0.05) and estimated oxygen shunt (r = 0.41, p < 0.05) and inversely correlated with partial pressure of arterial oxygen (PaO2) while breathing 100% O2 (r = -0.43, p < 0.05). The 99mTc-MAA was positive in 20.6% (7/36) of the patients with HPS and lung disease. The brain uptake of 99mTc-MAA was not associated with mortality and normalized in all cases six months after LT. CONCLUSIONS The 99mTc-MAA is a low sensitivity test for the diagnosis of HPS that can be useful in patients who have concomitant lung disease and in severe to very severe cases of HPS. It was not related to mortality, and brain uptake normalized after LT.
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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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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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Soulaidopoulos S, Goulis I, Giannakoulas G, Panagiotidis T, Doumtsis P, Karasmani A, Oikonomou T, Tzoumari T, Karvounis H, Cholongitas Ε. Hepatopulmonary syndrome is associated with the presence of hepatocellular carcinoma in patients with decompensated cirrhosis. Ann Gastroenterol 2016; 30:225-231. [PMID: 28243044 PMCID: PMC5320036 DOI: 10.20524/aog.2016.0117] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 11/17/2016] [Indexed: 12/16/2022] Open
Abstract
Background Hepatopulmonary syndrome (HPS) is a relatively common complication in patients with decompensated cirrhosis. Our aim was to evaluate the prevalence of HPS, its clinical impact, and the possible association between HPS and characteristics of patients with decompensated cirrhosis. Methods Patients with stable decompensated cirrhosis admitted to our department and assessed for HPS were included. For each patient, several clinical, laboratory and echocardiographic parameters as well as renal function were recorded. The severity of liver disease was evaluated according to the Model for End-stage Liver Disease and Child-Pugh scores, and renal function was assessed using 51chromium complexed with ethylene diamine tetracetic acid. In addition, the short synacthen test was performed in each patient to evaluate the adrenal function. Results Sixty-three patients were enrolled, 26 (41.3%) of whom diagnosed with HPS. In multivariate analysis, the presence of hepatocellular carcinoma [odds ratio (OR) 8.1, 95% confidence interval (CI) 5.3-27.9, P=0.045] and salivary cortisol at T60 (60 min after the intravenous injection of 250 μg corticotropin) (OR 0.88, 95%CI 0.71-0.98, P=0.045) were the factors independently associated with HPS. T60 salivary cortisol had relatively good discriminative ability for the presence of HPS (area under the curve=0.73). The presence of HPS was not associated with the outcome (P=0.22). Conclusion In our cohort of patients with decompensated cirrhosis, the presence of hepatocellular carcinoma and T60 salivary cortisol were the only factors independently associated with HPS.
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Affiliation(s)
- Stergios Soulaidopoulos
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - Ioannis Goulis
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - George Giannakoulas
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki (George Giannakoulas, Theofilos Panagiotidis, Haralampos Karvounis), Thessaloniki, Greece
| | - Theofilos Panagiotidis
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki (George Giannakoulas, Theofilos Panagiotidis, Haralampos Karvounis), Thessaloniki, Greece
| | - Petros Doumtsis
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - Areti Karasmani
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - Theodora Oikonomou
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - Theodora Tzoumari
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
| | - Haralampos Karvounis
- First Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki (George Giannakoulas, Theofilos Panagiotidis, Haralampos Karvounis), Thessaloniki, Greece
| | - Εvangelos Cholongitas
- 4 Department of Internal Medicine, Hippokration University Hospital, Medical School, Aristotle University of Thessaloniki (Stergios Soulaidopoulos, Ioannis Goulis, Petros Doumtsis, Areti Karasmani, Theodora Oikonomou, Theodora Tzoumari, Evangelos Cholongitas)
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Orozco-Delgado M, López-Cantero M, Zampella V, Vicente R, Galán J. Predictors of mortality and early detection strategies for hepatopulmonary syndrome in liver transplant patients. COLOMBIAN JOURNAL OF ANESTHESIOLOGY 2016. [DOI: 10.1016/j.rcae.2016.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Factores predictores de mortalidad y estrategias de detección precoz de síndrome hepatopulmonar en pacientes trasplantados hepáticos. COLOMBIAN JOURNAL OF ANESTHESIOLOGY 2016. [DOI: 10.1016/j.rca.2016.06.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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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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Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome. Sci Rep 2016; 6:30833. [PMID: 27480323 PMCID: PMC4969600 DOI: 10.1038/srep30833] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Accepted: 07/11/2016] [Indexed: 02/08/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is a defective liver-induced pulmonary vascular disorder with massive pulmonary microvascular dilation and excessive proliferation of pulmonary microvascular endothelial cells (PMVECs). Growing evidence suggests that autophagy is involved in pulmonary diseases, protectively or detrimentally. Thus, it is interesting and important to explore whether autophagy might be involved in and critical in HPS. In the present study, we report that autophagy was activated in common bile duct ligation (CBDL) rats and cultured pulmonary PMVECs induced by CBDL rat serum, two accepted in vivo and in vitro experimental models of HPS. Furthermore, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) significantly alleviated pathological alterations and typical symptom of HPS in CBDL rats in vivo, and consistently 3-MA significantly attenuated the CBDL rat serum-induced excessive proliferation of PMVECs in vitro. All these changes mediated by 3-MA might explain the observed prominent improvement of pulmonary appearance, edema, microvascular dilatation and arterial oxygenation in vivo. Collectively, these results suggest that autophagy activation may play a critical role in the pathogenesis of HPS, and autophagy inhibition may have a therapeutic potential for this disease.
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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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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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Predictors of mortality and early detection strategies for hepatopulmonary syndrome in liver transplant patients☆. COLOMBIAN JOURNAL OF ANESTHESIOLOGY 2016. [DOI: 10.1097/01819236-201644040-00009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Abstract
Objective: To investigate bilirubin-induced lung alveolar epithelial cell injury together with the protection afforded by dexmedetomidine. Design: Prospective, randomized, controlled study. Setting: Research laboratory. Subjects: Sprague Dawley rats. Interventions: Alveolar epithelial A549 cell lines were cultured and received bilirubin (from 0 to 160 μM) to explore the protective pathway of dexmedetomidine on bilirubin-induced alveolar epithelial cell injury assessed by immunochemistry and flow cytometry. Sprague-Dawley rats were subjected to common bile duct ligation surgery to explore the protective effect of dexmedetomidine on hyperbilirubinemia-induced alveolar epithelial cell injury and respiratory failure in comparison with the Sham (subjected to the surgery procedure but without bile duct ligation) or dexmedetomidine control (only received intraperitoneal injection of dexmedetomidine). Measurements and Main Results: In vitro, dexmedetomidine reversed the collapse of mitochondrial membrane potential (Δψm), upregulation of cytochrome C, B cell leukemia 2 associated X protein, and cleaved-caspase 3 and 9 in A549 epithelial cells with bilirubin challenge. Furthermore, dexmedetomidine reversed the arrest of cell cycle and the downregulation of the transforming growth factorβ, phosphorylated mammalian target of rapamycin, and p42/44 mitogen-activated protein kinase induced by bilirubin. In vivo, pulmonary edema and inflammation were found after common bile duct ligation. Bilirubin and Paco2 were significantly increased, and oxygen (Pao2) was significantly decreased in the blood of common bile duct ligation rats from the postsurgery day 7 to day 21 when compared with those in the sham controls, respectively (p < 0.01). Daily intraperitoneal injection of dexmedetomidine significantly alleviated the lung edema and injury and prevented respiratory failure. Conclusion: Our data both in vitro and in vivo demonstrated that dexmedetomidine protected alveolar epithelial cell from bilirubin-induced injury. Dexmedetomidine may be a good choice of anesthetic/sedative for patients with chronic liver disease during the perioperative period.
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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
Patients with cirrhosis and portal hypertension are at an increased risk of the development of circulatory dysfunction that may potentially result in multiple organ failure. Apart from the liver, this may involve the heart, lungs, kidneys, the immune system, the adrenal glands, and other organ systems. As the disease progresses, the circulation becomes hyperdynamic, and signs of cardiac, pulmonary, and renal dysfunction are observed, in addition to reduced survival. Infections and an altered cardiac function known as cirrhotic cardiomyopathy may be precipitators for the development of other complications such as hepatorenal syndrome. In patients with chronic organ dysfunction, various precipitating events may induce an acute-on-chronic renal failure and acute-on-chronic liver failure that negatively affect the prognosis. Future research on the pathophysiologic mechanisms of the complications and the precipitating factors is essential to understand the basics of the treatment of these challenging conditions. The aim of the present review is to focus on the development and precipitating factors of various organ failures in patients with decompensated cirrhosis.
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