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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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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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Sayadi A, Duhaut L, Robert F, Savale L, Coilly A. [Hepatopulmonary syndrome]. Rev Med Interne 2024; 45:156-165. [PMID: 37005097 DOI: 10.1016/j.revmed.2023.03.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Revised: 03/07/2023] [Accepted: 03/17/2023] [Indexed: 04/03/2023]
Abstract
The hepatopulmonary syndrome (HPS) is one of the lung diseases associated with cirrhosis and portal hypertension. It should be discussed for any dyspnea in cirrhotic patients. HPS is a pulmonary vascular disease characterized by intrapulmonary vascular dilatations (IPVD). The pathogenesis is complex and seems to rely on communications between the portal and pulmonary circulations. The diagnosis is based on a triad of liver disease and portal hypertension, evidence of IPVDs, and impaired gas exchange (alveolar-arterial oxygen difference [A-aO2]≥15mmHg). HPS impairs prognosis (23% survival at 5years) and patients' quality of life. Liver transplantation (LT) allows regression of IPDVD in almost 100% of cases, normalization of gas exchange and improves survival with a 5-year post-LT survival between 76 and 87%. It is the only curative treatment, indicated in patients with severe HPS, defined by an arterial partial pressure of oxygen (PaO2) below 60mmHg. When LT is not indicated or feasible, long-term oxygen therapy may be proposed as a palliative treatment. A better understanding of the pathophysiological mechanisms is needed to improve the therapeutic possibilities in a near future.
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Affiliation(s)
- A Sayadi
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France
| | - L Duhaut
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France
| | - F Robert
- Inserm UMR_S 999, 94270 Le Kremlin-Bicêtre, France
| | - L Savale
- Inserm UMR_S 999, 94270 Le Kremlin-Bicêtre, France; Service de pneumologie, hôpital Bicêtre, université Paris-Saclay, AP-HP, 94270 Le Kremlin-Bicêtre, France
| | - A Coilly
- UMR-S 1193, hôpital Paul-Brousse, centre hépato-biliaire, université Paris-Saclay, AP-HP, 94800 Villejuif, France.
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Georgakopoulou VE, Asimakopoulou S, Cholongitas E. Pulmonary function testing in patients with liver cirrhosis (Review). MEDICINE INTERNATIONAL 2023; 3:36. [PMID: 37533800 PMCID: PMC10391595 DOI: 10.3892/mi.2023.96] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 06/29/2023] [Indexed: 08/04/2023]
Abstract
Liver cirrhosis is a common long-term outcome of chronic hepatic inflammation. Patients with liver cirrhosis may also have pulmonary complications. There are several reasons for pulmonary dysfunction in liver cirrhosis, including intrinsic cardiopulmonary dysfunction unrelated to liver disease and specific disorders related to the presence of liver cirrhosis and/or portal hypertension. The most prevalent and clinically significant pulmonary complications are hepatic hydrothorax, hepatopulmonary syndrome, spontaneous pulmonary empyema and portopulmonary hypertension. Pulmonary function tests (PFTs) have traditionally been used to assess the lung function of patients with liver cirrhosis. To the best of our knowledge, the present review is the first to detail all types of PFTs performed in patients with liver cirrhosis and discuss their clinical significance. Patients with liver cirrhosis have reduced values of spirometric parameters, diffusion capacity for carbon monoxide (DLCO), lung volumes, maximal inspiratory pressure and maximal expiratory pressure. Furthermore, they have a higher closing volume, a greater airway occlusion pressure 0.1 sec after the onset of inspiratory flow and greater exhaled nitric oxide values. In order to improve pulmonary function, patients with ascites may require therapeutic paracentesis. Such findings should be considered when evaluating individuals with liver disease, particularly those who may require surgery. Poor lung function, particularly restrictive lung disease, can have an impact on post-transplant outcomes, such as ventilator time, length of hospital duration and post-operative pulmonary complications; thus, the transplant care team needs to be aware of its prevalence and relevance.
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Affiliation(s)
- Vasiliki Epameinondas Georgakopoulou
- Department of Infectious Diseases and COVID-19 Unit, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Stavroula Asimakopoulou
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
| | - Evangelos Cholongitas
- First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece
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Raevens S, Boret M, Fallon MB. Hepatopulmonary syndrome. JHEP REPORTS : INNOVATION IN HEPATOLOGY 2022; 4:100527. [PMID: 36035361 PMCID: PMC9403489 DOI: 10.1016/j.jhepr.2022.100527] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/10/2022] [Accepted: 06/15/2022] [Indexed: 11/25/2022]
Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of liver disease, which adversely affects prognosis. The disease is characterised by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange. A complex interaction between the liver, the gut and the lungs, predominately impacting pulmonary endothelial cells, immune cells and respiratory epithelial cells, is responsible for the development of typical pulmonary alterations seen in HPS. Liver transplantation is the only therapeutic option and generally reverses HPS. Since the implementation of the model for end-stage liver disease (MELD) standard exception policy, outcomes in patients with HPS have been significantly better than they were in the pre-MELD era. This review summarises current knowledge and highlights what’s new regarding the diagnosis and management of HPS, and our understanding of pathogenesis based on experimental models and translational studies.
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Parikh H, Lui E, Faughnan ME, Al-Hesayen A, Segovia S, Gupta S. Supine vs upright exercise in patients with hepatopulmonary syndrome and orthodeoxia: study protocol for a randomized controlled crossover trial. Trials 2021; 22:683. [PMID: 34625098 PMCID: PMC8500814 DOI: 10.1186/s13063-021-05633-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 09/15/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The hepatopulmonary syndrome (HPS) is a pulmonary complication of liver disease found in 10 to 32% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations and abnormal oxygenation. Liver transplantation is the only effective therapy for this disease. Patients with HPS have significant exercise limitations, impacting their quality of life and associated with poor liver transplant outcomes. Many patients with HPS exhibit orthodeoxia-an improvement in oxygenation in the supine compared to the upright position. We hypothesize that exercise capacity will be superior in the supine compared to the upright position in such patients. METHODS We propose a randomized controlled crossover trial in patients with moderate HPS (PaO2 < 80 mmHg) and orthodeoxia (supine to upright PaO2 decrease > 4 mmHg) comparing the effect of supine vs upright position on exercise. Patients with pulmonary hypertension, FEV1/FVC ratio < 0.65, significant coronary artery disease, disorders preventing or contraindicating use of a cycle ergometer, and/or moderate or severe ascites will be excluded. Participants will be randomized to cycle ergometry in either the supine or upright position. After a short washout period (a minimum of 1 day to a maximum of 4 weeks), participants will crossover and perform an exercise in the alternate position. Exercise will be performed at a constant work rate of 70-85% of the predicted peak work rate until the "stopping time" is reached, defined by exhaustion, profound desaturation, or safety concerns (drop in systolic blood pressure or life-threatening arrhythmia). The primary outcome will be the difference in the stopping time between exercise positions, compared with a repeated measures analysis of variance method with a mixed effects model approach. The model will be adjusted for period effects. P < 0.05 will be considered statistically significant. DISCUSSION HPS patients have hypoxemia leading to significant exercise limitations. If our study is positive, a supine exercise regimen could become a routine prescription for patients with HPS and orthodeoxia, enabling them to exercise more effectively. Future studies could explore the corresponding effects of a supine exercise training regimen on physiologic variables such as long-term exercise capacity, quality of life, dyspnea, and liver transplantation outcomes. TRIAL REGISTRATION ClinicalTrials.gov Protocol Registration and Results System (PRS) NCT04004104 . Registered on 1 July 2019.
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Affiliation(s)
- Harsh Parikh
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada
| | - Eric Lui
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada
| | - Marie E Faughnan
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada.,Department of Medicine, University of Toronto, Toronto, Canada.,Division of Respirology, St. Michael's Hospital, Toronto, Canada
| | - Abdul Al-Hesayen
- Department of Medicine, University of Toronto, Toronto, Canada.,Division of Cardiology, St Michael's Hospital, Toronto, Canada
| | | | - Samir Gupta
- Li Ka Shing Knowledge Institute, Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, Canada. .,Department of Medicine, University of Toronto, Toronto, Canada. .,Division of Respirology, St. Michael's Hospital, Toronto, Canada.
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Maruyama H, Shiina S. Connection between HPS and ACLF: a solution of chaos? Hepatol Int 2021; 15:1049-1052. [PMID: 34606063 PMCID: PMC8488067 DOI: 10.1007/s12072-021-10255-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2021] [Accepted: 09/11/2021] [Indexed: 11/30/2022]
Affiliation(s)
- Hitoshi Maruyama
- Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
| | - Shuichiro Shiina
- Department of Gastroenterology, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan
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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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Mendoza N, Rivas E, Rodriguez-Roisin R, Garcia T, Bruguera M, Agusti A, Faner R. Liver epigenome changes in patients with hepatopulmonary syndrome: A pilot study. PLoS One 2021; 16:e0245046. [PMID: 33630849 PMCID: PMC7906328 DOI: 10.1371/journal.pone.0245046] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 12/22/2020] [Indexed: 11/25/2022] Open
Abstract
The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.
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Affiliation(s)
- Nuria Mendoza
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Eva Rivas
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Department of Anesthesia, Hospital Clinic, Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
| | - Roberto Rodriguez-Roisin
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Tamara Garcia
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
| | - Miquel Bruguera
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Alvar Agusti
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Respiratory Institute, Hospital Clinic, Barcelona, Spain
- University of Barcelona, Barcelona, Spain
| | - Rosa Faner
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
- * E-mail:
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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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Affiliation(s)
- Samir Gupta
- Department of Medicine (Gupta), University of Toronto; Division of Respirology (Gupta), St. Michael's Hospital; Keenan Research Centre for Biomedical Science (Gupta), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont.; Pulmonary and Gastroenterology/Hepatology Division (Krowka), Mayo Clinic, Rochester, Minn.
| | - Michael J Krowka
- Department of Medicine (Gupta), University of Toronto; Division of Respirology (Gupta), St. Michael's Hospital; Keenan Research Centre for Biomedical Science (Gupta), Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ont.; Pulmonary and Gastroenterology/Hepatology Division (Krowka), Mayo Clinic, Rochester, Minn
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12
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Tsauo J, Zhao H, Zhang X, Ma H, Jiang M, Weng N, Li X. Changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome. Eur Radiol 2019; 29:3273-3280. [PMID: 30506220 DOI: 10.1007/s00330-018-5840-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Revised: 09/18/2018] [Accepted: 10/19/2018] [Indexed: 02/05/2023]
Abstract
OBJECTIVES To evaluate the changes in arterial oxygenation after portal decompression in Budd-Chiari syndrome (BCS) patients with hepatopulmonary syndrome (HPS). METHODS From June 2014 to June 2015, all patients with BCS who underwent balloon angioplasty or transjugular intrahepatic portosystemic shunt (TIPS) creation at our institution were eligible for inclusion in this study. Arterial blood gas analysis was performed with the patient in an upright position and breathing room air at 2-3 days and 1 and 3 months after the procedure. RESULTS Eleven patients with HPS and 14 patients without HPS were included in this study. The procedure was technically successful in 24 patients. One patient with HPS had technically unsuccessful TIPS creation. Reobstruction or TIPS dysfunction was not detected in any patient within 3 months after the procedure. For patients with HPS, the alveolar-arterial oxygen gradient (A-aO2) remained comparable to baseline 2-3 days after the procedure (-3.2 ± 11.9 mmHg; p = .412), significantly improved 1 month after the procedure (-11.7 ± 6.4 mmHg; p < .001), and then returned to baseline 3 months after the procedure (-1.3 ± 12.5 mmHg; p = .757). For patients without HPS, the A-aO2 remained comparable to baseline at all three time points after the procedure (+1.4 ± 8.3 mmHg, +3.5 ± 8.1 mmHg, and +1.3 ± 8.2 mmHg; p = .543, p = .137, and p = .565). CONCLUSIONS Arterial oxygenation transiently improves after portal decompression in BCS patients with HPS. KEY POINTS • Intrapulmonary vascular dilation and hepatopulmonary syndrome are common in patients with Budd-Chiari syndrome. • Arterial oxygenation transiently improves after portal decompression in Budd-Chiari syndrome patients with hepatopulmonary syndrome.
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Affiliation(s)
- Jiaywei Tsauo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - He Zhao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Xiaowu Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China
| | - Huaiyuan Ma
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Mingshan Jiang
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Ningna Weng
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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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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Tsauo J, Zhao H, Zhang X, Ma H, Jiang M, Weng N, Li X. Effect of Transjugular Intrahepatic Portosystemic Shunt Creation on Pulmonary Gas Exchange in Patients with Hepatopulmonary Syndrome: A Prospective Study. J Vasc Interv Radiol 2019; 30:170-177. [PMID: 30717947 DOI: 10.1016/j.jvir.2018.09.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 09/10/2018] [Accepted: 09/11/2018] [Indexed: 12/23/2022] Open
Abstract
PURPOSE To evaluate effect of transjugular intrahepatic portosystemic shunt (TIPS) creation on pulmonary gas exchange in patients with hepatopulmonary syndrome (HPS). MATERIALS AND METHODS All patients with cirrhosis or Budd-Chiari syndrome undergoing elective TIPS creation at a single institution between June 2014 and June 2015 were eligible for inclusion. Twenty-three patients with HPS (age 55.0 y ± 14.4; 11 men; Model for End-Stage Liver Disease score 10.2 ± 2.7) who achieved technical success were included in the analysis. Diagnosis of HPS was established by contrast-enhanced echocardiography demonstrating intrapulmonary vascular dilatation and arterial blood gas analysis demonstrating arterial oxygenation defects. RESULTS Mean portosystemic gradient was reduced from 21.7 mm Hg ± 8.3 before TIPS creation to 10.8 mm Hg ± 5.1 after TIPS creation. Among the 5 (21.7%) patients who experienced dyspnea, 4 (80.0%) reported improvement after TIPS creation. This improvement was not maintained at 3 months after TIPS creation in 2 (50.0%) patients. Compared with before TIPS creation, mean change in alveolar-arterial oxygen gradient for patients with HPS was statistically significant at 1 month (-9.2 mm Hg ± 8.0; P < .001) after TIPS creation, but not at 2-3 days (-0.9 mm Hg ± 10.5; P = .678) or 3 months (-3.4 mm Hg ± 11.8; P = .179) after TIPS creation. CONCLUSIONS TIPS creation can transiently improve pulmonary gas exchange in patients with HPS.
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Affiliation(s)
- Jiaywei Tsauo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - He Zhao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaowu Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huaiyuan Ma
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Mingshan Jiang
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Ningna Weng
- Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Institute of Interventional Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
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Riou M, Jutant EM, Mignard X, Canuet M, Humbert M, Sitbon O, Savale L, Montani D. Hépatopathies et maladies vasculaires pulmonaires. Rev Med Interne 2018; 39:925-934. [DOI: 10.1016/j.revmed.2018.07.015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Accepted: 07/23/2018] [Indexed: 12/26/2022]
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Burra P, Giannini EG, Caraceni P, Ginanni Corradini S, Rendina M, Volpes R, Toniutto P. Specific issues concerning the management of patients on the waiting list and after liver transplantation. Liver Int 2018; 38:1338-1362. [PMID: 29637743 DOI: 10.1111/liv.13755] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Accepted: 03/27/2018] [Indexed: 02/06/2023]
Abstract
The present document is a second contribution collecting the recommendations of an expert panel of transplant hepatologists appointed by the Italian Association for the Study of the Liver (AISF) concerning the management of certain aspects of liver transplantation, including: the issue of prompt referral; the management of difficult candidates; malnutrition; living related liver transplants; hepatocellular carcinoma; and the role of direct acting antiviral agents before and after transplantation. The statements on each topic were approved by participants at the AISF Transplant Hepatology Expert Meeting organized by the Permanent Liver Transplant Commission in Mondello on 12-13 May 2017. They are graded according to the GRADE grading system.
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Affiliation(s)
- Patrizia Burra
- Multivisceral Transplant Unit, University Hospital, Padova, Italy
| | - Edoardo G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Ospedale Policlinico San Martino, Genoa, Italy
| | | | | | | | - Riccardo Volpes
- Hepatology and Gastroenterology Unit, ISMETT-IRCCS, Palermo, Italy
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17
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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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18
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Rodríguez-Roisin R, Krowka MJ, Agustí A. Hepatopulmonary Disorders: Gas Exchange and Vascular Manifestations in Chronic Liver Disease. Compr Physiol 2018; 8:711-729. [PMID: 29687908 DOI: 10.1002/cphy.c170020] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
This review concentrates on the determinants of gas exchange abnormalities in liver-induced pulmonary vascular disorders, more specifically in the hepatopulmonary syndrome. Increased alveolar-arterial O2 difference, with or without different levels of arterial hypoxemia, and reduced diffusing capacity represent the most characteristic gas exchange disturbances in the absence of cardiac and pulmonary comorbidities. Pulmonary gas exchange abnormalities in the hepatopulmonary syndrome are unique encompassing all three pulmonary factors determining arterial PO2 , that is, ventilation-perfusion imbalance, increased intrapulmonary shunt and oxygen diffusion limitation that, combined, interplay with two relevant nonpulmonary determinants, that is, increased total ventilation and high cardiac output. Behind the complexity of this lung-liver association there is an abnormal pulmonary vascular tone that combines inhibition of hypoxic pulmonary vasoconstriction with a reduced (or blunted) hypoxic vascular response. The pathology and pathobiology include the presence of intrapulmonary vascular dilatations with or without pulmonary vascular remodeling, i.e. angiogenesis. Liver transplantation, the only effective therapeutic approach to successfully improve and resolve the vast majority of complications induced by the hepatopulmonary syndrome, along with a large list of frustrating pharmacologic interventions, are also reviewed. Another liver-induced pulmonary vascular disorder with less gas exchange involvement, such as portopulmonary hypertension, is also considered. © 2018 American Physiological Society. Compr Physiol 8:711-729, 2018.
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Affiliation(s)
- Robert Rodríguez-Roisin
- Department of Medicine, Universitat de Barcelona (UB), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona
| | - Michael J Krowka
- Division of Pulmonary and Critical Care, Transplant Research Center, Mayo Clinic, Rochester, MN, US
| | - Alvar Agustí
- Service of Pneumology, Respiratory Institute, Hospital Clínic, UB, Centro de Investigaciones Biomédicas en Red sobre Enfermedades Respiratorias (CIBERES), Barcelona
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19
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Suk KT, Kim MY, Jeong SW, Jang JY, Jang YO, Baik SK. Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study. Dig Dis Sci 2018; 63:248-256. [PMID: 29192374 DOI: 10.1007/s10620-017-4868-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Accepted: 11/23/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND/AIMS Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. METHODS A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. RESULTS Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 ± 0.02, 1.02 ± 0.18, 2.86 ± 0.77, and 6.56 ± 1.46 EU/mL, p < 0.001) and LBP (7026 ± 3336, 11,445 ± 1247, 11,947 ± 1164, and 13,791 ± 2032 ng/mL, p = 0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83 ± 0.17, 2.62 ± 0.22, 3.69 ± 0.28, and 4.29 ± 0.34 pg/mL, p < 0.001), demonstrating a significant difference between each grade (p < 0.05). CONCLUSIONS HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS.
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Affiliation(s)
- Ki Tae Suk
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Moon Young Kim
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, South Korea
| | - Soung Won Jeong
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Jae Young Jang
- Institute for Digestive Research, Digestive Disease Center, Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, South Korea
| | - Yoon Ok Jang
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Soon Koo Baik
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, 20 Ilsan-ro, Wonju, 26426, South Korea.
- Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, South Korea.
- Institute of Evidence Based Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea.
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Zhao H, Liu F, Yue Z, Wang L, Fan Z, He F. Clinical efficacy of transjugular intrahepatic portosystemic shunt in the treatment of hepatopulmonary syndrome. Medicine (Baltimore) 2017; 96:e9080. [PMID: 29245324 PMCID: PMC5728939 DOI: 10.1097/md.0000000000009080] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Transjugular intrahepatic portosystemic shunt (TIPS) reduces the portal venous pressure of patients with hepatopulmonary syndrome (HPS).To describe the patients who underwent TIPS for the treatment of HPS.A retrospective study was performed on 81 patients with HPS and gastrointestinal hemorrhage treated with TIPS. Thirty patients underwent TIPS through the main portal vein (group A), 24 through the left branch of the portal vein (group B), and 27 through the right branch of the portal vein (group C). The partial pressure of arterial oxygen (PaO2), alveolar-to-arterial oxygen partial pressure gradient (A-aPO2), oxygen saturation (SO2), and complications were recorded and compared. The survival rate for each group was calculated.The technical success rate was 100% in the 3 groups. Preoperative portal vein pressure showed no significant differences between the 3 groups, which was decreased post-TIPS operation. In group A, PaO2 and SO2 were higher in 15 days and 3 months postoperative than preoperative (P < .05), whereas A-aPO2 was lower (P < .05). No difference occurred between 12 months post- and preoperative group. In group C, PaO2 and SO2 did not alter significantly at each time point after operation (P > .05), whereas A-aPO2 decreased at 3 months (P = .041) than preoperative. In group B, all indicators at each follow-up time point after TIPS were improved significantly as compared with the preoperative group (P < .05), which showed an excellent effect on hypoxemia treatment. Although the 1-year survival rate of 3 groups of patients was 92.85%, 90.90%, and 91.67%, respectively, the rate of hepatic encephalopathy and hepatic myelopathy was 33.33% (10/30), 16.67% (4/24), and 33.33% (9/27) after TIPS.TIPS reduced the pressure of the portal vein effectively and alleviated hypoxemia in most HPS patients successfully. Thus, the left branch of the portal vein is optimal for TIPS owing to fewer complications and efficacy in improving PaO2 as compared with the main portal vein and right branch.
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Gonçalves-Macedo L, Lopes EP, Domingues ALC, Markman B, Mota VG, Luna CF. Schistosomiasis and hepatopulmonary syndrome: the role of concomitant liver cirrhosis. Mem Inst Oswaldo Cruz 2017; 112:469-473. [PMID: 28591307 PMCID: PMC5452483 DOI: 10.1590/0074-02760160383] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 03/13/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hepatopulmonary syndrome (HPS) is defined as an oxygenation defect induced by intrapulmonary vasodilation in patients with liver disease or portal hypertension. It is investigated in patients with liver cirrhosis and less frequently in those with portal hypertension without liver cirrhosis, as may occur in hepatosplenic schistosomiasis (HSS). OBJECTIVES To investigate the prevalence of HPS in patients with HSS, and to determine whether the occurrence of HPS is influenced by concomitant cirrhosis. METHODS We evaluated patients with HSS with or without concomitant liver cirrhosis. All patients underwent laboratory testing, ultrasound, endoscopy, contrast echocardiography, and arterial blood gas analysis. FINDINGS Of the 121 patients with HSS, 64 were also diagnosed with liver cirrhosis. HPS was diagnosed in 42 patients (35%) and was more frequent among patients with concomitant liver cirrhosis than in those without cirrhosis (42% vs. 26%), but the difference was not significant (p = 0.069). HPS was more common in those with spider naevi, Child-Pugh classes B or C and high model for end stage liver disease (MELD) scores (p < 0.05 each). MAIN CONCLUSIONS The prevalence of HPS was 35% in this study. The occurrence of liver cirrhosis concomitantly with HSS may have influenced the frequency of patients presenting with HPS.
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Affiliation(s)
- Liana Gonçalves-Macedo
- Universidade Federal de Pernambuco, Programa de Pós-Graduação em Medicina Tropical, Recife, PE, Brasil
| | - Edmundo Pessoa Lopes
- Universidade Federal de Pernambuco, Departamento de Medicina Clínica, Serviço de Gastroenterologia e Hepatologia, Recife, PE, Brasil
| | - Ana Lucia Coutinho Domingues
- Universidade Federal de Pernambuco, Departamento de Medicina Clínica, Serviço de Gastroenterologia e Hepatologia, Recife, PE, Brasil
| | - Brivaldo Markman
- Universidade Federal de Pernambuco, Departamento de Medicina Clínica, Serviço de Cardiologia e Ecocardiografia, Recife, PE, Brasil
| | - Vitor Gomes Mota
- Universidade Federal de Pernambuco, Departamento de Medicina Clínica, Serviço de Cardiologia e Ecocardiografia, Recife, PE, Brasil
| | - Carlos Feitosa Luna
- Fundação Oswaldo Cruz-Fiocruz, Laboratório de Métodos Quantitativos em Saúde, Recife, PE, Brasil
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22
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Abstract
Cirrhosis, the twelfth leading cause of death, accounts for 1.1% of all deaths in the United States. Although there are multiple pulmonary complications associated with liver disease, the most important complications that cause significant morbidity and mortality are hepatopulmonary syndrome, hepatic hydrothorax, and portopulmonary hypertension. Patients with cirrhosis who complain of dyspnea should be evaluated for these complications. This article reviews these complications.
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Affiliation(s)
- Vijaya S Ramalingam
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA.
| | - Sikandar Ansari
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
| | - Micah Fisher
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, Emory Clinic 'A', 1365 Clifton Road, Northeast 4th Floor, Atlanta, GA 30322, USA
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23
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Puttappa A, Sheshadri K, Fabre A, Imberger G, Boylan J, Ryan S, Iqbal M, Conlon N. Prolonged Unexplained Hypoxemia as Initial Presentation of Cirrhosis: A Case Report. AMERICAN JOURNAL OF CASE REPORTS 2017; 18:1-6. [PMID: 28042141 PMCID: PMC5221740 DOI: 10.12659/ajcr.900530] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Patient: Male, 43 Final Diagnosis: Hepatopulmonary syndrome Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Gastroenterology and Hepatology
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Affiliation(s)
- Anand Puttappa
- Department of Anaesthesia and Intensive Care, St Vincent's University Hospital, Dublin, Ireland
| | - Kumaraswamy Sheshadri
- Department of Anaesthesia and Intensive Care, St Vincent's University Hospital, Dublin, Ireland
| | - Aurelie Fabre
- Department of Histopathology, St Vincent's University Hospital, Dublin, Ireland
| | - Georgina Imberger
- Department of Anaesthesia and Pain Medicine, Western Health, Melbourne, Australia
| | - John Boylan
- Department of Anaesthesia and Intensive Care, St Vincent's University Hospital, Dublin, Ireland
| | - Silke Ryan
- Department of Respiratory and Sleep Medicine, St Vincent's University Hospital, Dublin, Ireland
| | - Masood Iqbal
- Department of Hepatology, St Vincent's University Hospital, Dublin, Ireland
| | - Niamh Conlon
- Department of Anaesthesia and Intensive Care, St Vincent's University Hospital, Dublin, Ireland
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24
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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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25
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Khositseth A, Treepongkaruna S, Khemakanok K, Teeraratkul S, Pansrimangkorn V, Thirapattaraphan C, Leelaudomlipi S. Intrapulmonary vascular dilation in children with chronic liver diseases: pre- and post-liver transplantation. Ann Hepatol 2016; 15:47-52. [PMID: 26626640 DOI: 10.5604/16652681.1184207] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND STUDY AIMS Chronic liver disease (CLD) can cause hepatopulmonary syndrome (HPS), defined as triad of liver disease, hypoxemia, and intrapulmonary vascular dilation (IPVD). The aim of this study was to determine the evidence of IPVD in a cohort of pediatric patients with CLD pre- and post-liver transplantation (LT). MATERIAL AND METHODS All pediatric patients with CLD listed for LT were studied. Pulse oxygen saturation (SpO(2)), technetium-99m-labeled macroaggregated albumin ((99m)Tc- MAA) perfusión scan (positive test: uptake of the isotope ≥ 6% in the brain), and echocardiography with saline bubble test (SBT) were performed. SBT was re-evaluated at 3-6 months after LT. Grading of SBT included grade 0 (no bubble), I (1-9 bubbles), grade II (10-20 bubbles), and grade III (> 20 bubbles). RESULTS Eighteen patients, median age 22.5 months (8-108), were enrolled. Most had biliary atresia (77.8%). Pre-LT, all patients had SpO(2) of 100% and none had positive (99)mTc- MAA perfusion scan. Two patients (11%) had negative SBT (grade 0), 1 (5.5%) had grade I, 3 (16.5%) had grade II, and 12 (67%) had grade III, respectively. Post-LT SBT became negative in all survivors (n = 16), (p = 0.0001). CONCLUSIONS Most cirrhotic children in this cohort study had evidence of IPVD by positive SBT. However, none of these met the criteria for diagnosis of HPS. This evidence of IPVD subsided after LT.
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Affiliation(s)
- Anant Khositseth
- Department of Surgery. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Suporn Treepongkaruna
- Department of Pediatrics. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Khemika Khemakanok
- Department of Surgery. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Sumate Teeraratkul
- Department of Surgery. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Vichai Pansrimangkorn
- Department of Surgery. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | | | - Surasak Leelaudomlipi
- Department of Pediatrics. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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26
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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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27
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Irei T, Onoe T, Das LK, Tanimine N, Ishiyama K, Ide K, Kobayashi T, Tashiro H, Ohdan H. Successful resolution of very severe hepatopulmonary syndrome following adult-to-adult living donor liver transplantation: Report of two cases. Hepatol Res 2015; 45:1041-1046. [PMID: 25355534 DOI: 10.1111/hepr.12445] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 10/08/2014] [Accepted: 10/21/2014] [Indexed: 02/08/2023]
Abstract
Hepatopulmonary syndrome (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Liver transplantation (LT) is a promising treatment for HPS; however, very severe HPS, which is defined by an arterial oxygen pressure (PaO2 ) of less than 50 mmHg and a right-left intrapulmonary shunt rate of more than 20%, may be a contraindication to LT, including living donor LT (LDLT). Here, we report two cases of decompensated liver cirrhosis with very severe HPS which were resolved after adult-to-adult LDLT including ABO-incompatible LDLT. Both patients required oxygen supportive therapy in combination with specialized respiratory care postoperatively, followed by improvement of oxygenation and substantial decreases of intrapulmonary shunt rate. These findings suggest very severe HPS can be resolved by LDLT, including ABO-incompatible LDLT, and reduced graft volume did not impede the reversal of intrapulmonary shunting. Our current report may indicate that adult-to-adult LDLT, including ABO-incompatible LDLT, is becoming an effective therapeutic method and prompt a review of previous reports as well as our own files with particular regard to the indication of LDLT for decompensated liver cirrhosis with very severe HPS.
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Affiliation(s)
- Toshimitsu Irei
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Institute for Clinical Research, National Hospital Organization Kure Medical Center/Chugoku Cancer Center, Kure, Japan
| | - Takashi Onoe
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.,Institute for Clinical Research, National Hospital Organization Kure Medical Center/Chugoku Cancer Center, Kure, Japan
| | - Lalit Kumar Das
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Naoki Tanimine
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kohei Ishiyama
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Kentaro Ide
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Tsuyoshi Kobayashi
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hirotaka Tashiro
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hideki Ohdan
- Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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28
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Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that may induce severe hypoxemia. Microvascular dilation and angiogenesis in the lung have been identified as pathologic features that drive gas exchange abnormalities in experimental HPS. Pulse oximetry is a useful screening test for HPS, which can guide subsequent use of arterial blood gases. Contrast-enhanced echocardiography, perfusion lung scanning, and pulmonary arteriography are three currently used diagnostic imaging modalities that identify the presence of intrapulmonary vascular abnormalities. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation. No medical therapy is established as effective for HPS. At the present time, liver transplantation is the only available treatment for HPS.
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Affiliation(s)
- Yong Lv
- Department of Liver Disease, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China,
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29
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Cuadrado A, Díaz A, Iruzubieta P, Salcines JR, Crespo J. Síndrome hepatopulmonar. GASTROENTEROLOGIA Y HEPATOLOGIA 2015; 38:398-408. [DOI: 10.1016/j.gastrohep.2015.02.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/08/2014] [Revised: 02/01/2015] [Accepted: 02/08/2015] [Indexed: 12/17/2022]
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30
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Raevens S, Geerts A, Van Steenkiste C, Verhelst X, Van Vlierberghe H, Colle I. Hepatopulmonary syndrome and portopulmonary hypertension: recent knowledge in pathogenesis and overview of clinical assessment. Liver Int 2015; 35:1646-60. [PMID: 25627425 DOI: 10.1111/liv.12791] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 01/17/2015] [Indexed: 12/14/2022]
Abstract
Hepatopulmonary syndrome and portopulmonary hypertension are cardiopulmonary complications, which are not infrequently seen in patients with liver disease and/or portal hypertension. These entities are both clinically and pathophysiologically different: the hepatopulmonary syndrome is characterized by abnormal pulmonary vasodilation and right-to-left shunting resulting in gas exchange abnormalities, whereas portopulmonary hypertension is caused by pulmonary artery vasoconstriction leading to hemodynamic failure. As both hepatopulmonary syndrome and portopulmonary hypertension are associated with significantly increased morbidity and mortality, and as these patients are commonly asymptomatic, all liver transplantation candidates should be actively screened for the presence of these two complications. The aim of is this review is to provide an overview on the hepatopulmonary syndrome and portopulmonary hypertension with primary focus on diagnosis and recent knowledge regarding pathogenesis and therapeutic targets.
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Affiliation(s)
- Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Anja Geerts
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Christophe Van Steenkiste
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.,Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Ghent, Belgium
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium
| | - Isabelle Colle
- Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium.,Department of Gastroenterology and Hepatology, Algemeen Stedelijk Ziekenhuis ASZ, Aalst, Belgium
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31
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Singh A, Pandey VK, Tandon M, Pandey CK. Dyskeratosis congenita induced cirrhosis for liver transplantation-perioperative management. Indian J Anaesth 2015; 59:312-4. [PMID: 26019357 PMCID: PMC4445154 DOI: 10.4103/0019-5049.156888] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Dyskeratosis congenita (DC) is an inherited disorder with progressive multisystem involvement. End stage liver disease (ESLD) in patients with DC is rare. We describe the perioperative management of a patient with DC induced ESLD and severe hepatopulmonary syndrome for living donor liver transplantation.
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Affiliation(s)
- Anshuman Singh
- Department of Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - V K Pandey
- Department of Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manish Tandon
- Department of Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - C K Pandey
- Department of Anesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
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32
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El-Habashy MM, Khamis AA, Kamel M, Essa A, Shehab-Eldin W, Shaban M. Hepatopulmonary syndrome in noncirrhotic patients with chronic viral hepatitis. THE EGYPTIAN JOURNAL OF BRONCHOLOGY 2014. [DOI: 10.4103/1687-8426.145728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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33
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Youn JK, Lee JM, Yi NJ, Choi YR, Suh SW, You T, Lee KW, Jung CW, Lee JW, Bae EJ, Ko JS, Kim WH, Park KW, Suh KS. Pediatric split liver transplantation after Fontan procedure in left isomerism combined with biliary atresia: a case report. Pediatr Transplant 2014; 18:E274-9. [PMID: 25263970 DOI: 10.1111/petr.12364] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/27/2014] [Indexed: 11/29/2022]
Abstract
LI is a subset of the heterotaxy syndrome and a rare birth defect that involves the heart and other organs. It can be combined with extracardiac abnormalities, especially BA. CHD can be associated with LI in up to 15% of cases, although it is rare in BA. Pediatric LT for a child with ESLD due to BA combined with LI and CHD is a challenging issue for a transplant surgeon. Herein, we report a successful split LT on a three-yr-old boy with LI who survived after a Fontan procedure due to single ventricle, but who suffered from HPS associated with BA.
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Affiliation(s)
- Joong Kee Youn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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34
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Yang W, Hu B, Wu W, Batra S, Blackburn MR, Alcorn JL, Fallon MB, Zhang J. Alveolar type II epithelial cell dysfunction in rat experimental hepatopulmonary syndrome (HPS). PLoS One 2014; 9:e113451. [PMID: 25419825 PMCID: PMC4242631 DOI: 10.1371/journal.pone.0113451] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2014] [Accepted: 10/24/2014] [Indexed: 12/18/2022] Open
Abstract
The hepatopulmonary syndrome (HPS) develops when pulmonary vasodilatation leads to abnormal gas exchange. However, in human HPS, restrictive ventilatory defects are also observed supporting that the alveolar epithelial compartment may also be affected. Alveolar type II epithelial cells (AT2) play a critical role in maintaining the alveolar compartment by producing four surfactant proteins (SPs, SP-A, SP-B, SP-C and SP-D) which also facilitate alveolar repair following injury. However, no studies have evaluated the alveolar epithelial compartment in experimental HPS. In this study, we evaluated the alveolar epithelial compartment and particularly AT2 cells in experimental HPS induced by common bile duct ligation (CBDL). We found a significant reduction in pulmonary SP production associated with increased apoptosis in AT2 cells after CBDL relative to controls. Lung morphology showed decreased mean alveolar chord length and lung volumes in CBDL animals that were not seen in control models supporting a selective reduction of alveolar airspace. Furthermore, we found that administration of TNF-α, the bile acid, chenodeoxycholic acid, and FXR nuclear receptor activation (GW4064) induced apoptosis and impaired SP-B and SP-C production in alveolar epithelial cells in vitro. These results imply that AT2 cell dysfunction occurs in experimental HPS and is associated with alterations in the alveolar epithelial compartment. Our findings support a novel contributing mechanism in experimental HPS that may be relevant to humans and a potential therapeutic target.
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Affiliation(s)
- Wenli Yang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Bingqian Hu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Wei Wu
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Sachin Batra
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Michael R. Blackburn
- Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Joseph L. Alcorn
- Division of Neonatology, Department of Pediatrics, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Michael B. Fallon
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
| | - Junlan Zhang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, United States of America
- * E-mail:
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35
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Respiratory muscle strength, hypoxemia and dyspnea in liver cirrhosis patients. EGYPTIAN JOURNAL OF CHEST DISEASES AND TUBERCULOSIS 2014. [DOI: 10.1016/j.ejcdt.2014.06.016] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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36
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Abstract
Hepatopulmonary syndrome (HPS) is a pulmonary complication observed in patients with chronic liver disease and/or portal hypertension, attributable to an intrapulmonary vascular dilatation that induces severe hypoxaemia. Considering the favourable long-term survival of HPS patients as well as the reversal of the syndrome with a functional liver graft, HPS is now an indication for orthotopic liver transplantation (OLT). Consequently, blood gas analysis and imaging techniques should be performed when cirrhotic patients present with shortness of breath as well as when OLT candidates are placed on the transplant waiting list. If the arterial partial pressure of oxygen (PaO2) is more than 10.7 kPa when breathing room air, HPS can be excluded and no other investigation is needed. When the PaO2 when breathing room air is 10.7 kPa or less, contrast-enhanced echocardiography should be performed to exclude pulmonary vascular dilatation. Lung function tests may also help detect additional pulmonary diseases that can contribute to impaired oxygenation. When contrast-enhanced echocardiography is negative, HPS is excluded and no follow-up is needed. When contrast-enhanced echocardiography is positive and PaO2 less than 8 kPa, patients should obtain a severity score that provides them with a reasonable probability of being transplanted within 3 months. In mild-to-moderate HPS (PaO2 8 to 10.6 kPa), periodic follow-up is recommended every 3 months to detect any further deterioration in PaO2. Although no intraoperative deaths have been directly attributed to HPS, oxygenation may worsen immediately following OLT due to volume overload and postoperative infections. Mechanical ventilation is often prolonged with an extended stay in the ICU. A high postoperative mortality (mostly within 6 months) is observed in this group of patients in comparison to non-HPS patients. However, the recovery of an adequate PaO2 within 12 months after OLT explains the similar outcome of HPS and non-HPS patients following OLT over a longer time period.
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Abstract
Nail abnormalities can arise in conjunction with or as a result of systematic pathologies. These pathologies include single-organ diseases, multisystemic diseases, and drug-induced insults. Clinical signs associated with these conditions include dyschromias, vascular alterations, periungual tissue changes, textural dystrophies, contour alterations, and growth-rate alterations. The associated systemic pathologies may affect any part of the nail apparatus, including the nail matrix, the nail plate, the nail bed, the underlying vasculature, and the periungual tissues. The anatomical location and extent of damage determine the clinically manifested anomaly.
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Abstract
The hepatopulmonary syndrome (HPS) is a pulmonary complication of cirrhosis and/or portal hypertension whereby patients develop hypoxemia as a result of alterations in pulmonary microvascular tone and architecture. HPS occurs in up to 30% of patients with cirrhosis. Although the degree of hypoxemia does not reliably correlate with the severity of liver disease, patients with HPS have a higher mortality than do patients with cirrhosis without the disorder. There has been progress into defining the mechanisms that lead to hypoxemia in HPS, but to date there are no therapeutic options for HPS aside from liver transplantation.
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Ghayumi SMA, Khalafi-Nezhad A, Jowkar Z. Pulse oximeter oxygen saturation in prediction of arterial oxygen saturation in liver transplant candidates. HEPATITIS MONTHLY 2014; 14:e15449. [PMID: 24748894 PMCID: PMC3989597 DOI: 10.5812/hepatmon.15449] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 12/06/2013] [Accepted: 02/22/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Liver transplant is the only definitive treatment for many patients with end stage liver disease. Presence and severity of preoperative pulmonary disease directly affect the rate of postoperative complications of the liver transplantation. Arterial blood gas (ABG) measurement, performed in many transplant centers, is considered as a traditional method to diagnose hypoxemia. Because ABG measurement is invasive and painful, pulse oximetry, a bedside, noninvasive and inexpensive technique, has been recommended as an alternative source for the ABG measurement. OBJECTIVES The aim of this study was to evaluate the efficacy of pulse oximetry as a screening tool in hypoxemia detection in liver transplant candidates and to compare the results with ABGs. PATIENTS AND METHODS Three hundred and ninety transplant candidates (237 males and 153 females) participated in this study. Arterial blood gas oxyhemoglobin saturation (SaO2) was recorded and compared with pulse oximetry oxyhemoglobin saturation (SpO2) results for each participants. The area under the curve (AUC) of receiver operating characteristic (ROC) curves was calculated by means of nonparametric methods to evaluate the efficacy of pulse oximetry to detect hypoxemia. RESULTS Roc-derived SpO2 threshold of ≤ 94% can predict hypoxemia (PaO2 < 60 mmHg) with a sensitivity of 100% and a specificity of 95%. Furthermore, there are associations between the ROC-derived SpO2 threshold of ≤ 97% and detection of hypoxemia (PaO2 < 70 mmHg) with a sensitivity of 100% and a specificity of 46%. The accuracy of pulse oximetry was not affected by the severity of liver disease in detection of hypoxemia. CONCLUSIONS Provided that SpO2 is equal to or greater than 94%, attained from pulse oximetry can be used as a reliable and accurate substitute for the ABG measurements to evaluate hypoxemia in patients with end stage liver disease.
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Affiliation(s)
| | - Abolfazl Khalafi-Nezhad
- Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran
- Corresponding Author: Abolfazl Khalafi-Nezhad, Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, IR Iran. Tel: +98-7116474316, Fax: +98-7116474316, E-mail:
| | - Zahra Jowkar
- Department of Operative Dentistry, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, IR Iran
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Machicao VI, Balakrishnan M, Fallon MB. Pulmonary complications in chronic liver disease. Hepatology 2014; 59:1627-37. [PMID: 24089295 DOI: 10.1002/hep.26745] [Citation(s) in RCA: 123] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 09/12/2013] [Indexed: 12/13/2022]
Abstract
The association of chronic liver disease with respiratory symptoms and hypoxia is well recognized. Over the last century, three pulmonary complications specific to chronic liver disease have been characterized: hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH). The development of portal hypertension is fundamental in the pathogenesis of each of these disorders. HPS is the most common condition, found in 5%-30% of cirrhosis patients, manifested by abnormal oxygenation due to the development of intrapulmonary vascular dilatations. The presence of HPS increases mortality and impairs quality of life, but is reversible with liver transplantation (LT). POPH is characterized by development of pulmonary arterial hypertension in the setting of portal hypertension, and is present in 5%-10% of cirrhosis patients evaluated for LT. Screening for POPH in cirrhosis patients eligible for LT is critical since severe POPH is a relative contraindication for LT. Patients with moderate POPH, who respond adequately to medical therapy, may benefit from LT, although sufficient controlled data are lacking. HH is a transudative pleural effusion seen in 5%-10% of cirrhosis patients, in the absence of cardiopulmonary disease. Diagnosis of HH should prompt consideration for LT, which is the ultimate treatment for HH. Conservative management includes salt restriction and diuretics, with thoracentesis and transjugular intrahepatic portosystemic shunt (TIPS) as second-line therapeutic options.
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Affiliation(s)
- Victor I Machicao
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, TX
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41
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Tumgor G. Cirrhosis and hepatopulmonary syndrome. World J Gastroenterol 2014; 20:2586-2594. [PMID: 24627594 PMCID: PMC3949267 DOI: 10.3748/wjg.v20.i10.2586] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2013] [Revised: 01/05/2014] [Accepted: 01/20/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation and arterial hypoxemia. HPS is reported to be present in 4% to 32% of adult patients with end-stage liver disease and in 9%-20% of children. The pathogenesis of HPS has not been clearly identified. Portal hypertension causes impairment in the perfusion of the bowel and increases the enteral translocation of Gram (-) bacteria and endotoxins. This stimulates the release of vasoactive mediators, such as tumor necrosis factor-alpha, heme oxygenase-derived carbon monoxide and nitric oxide. Genetic alterations have not been associated with this syndrome yet; however, cytokines and chemokines have been suggested to play a role. Recently, it was reported that cumulated monocytes lead to the activation of vascular endothelial growth factor-dependent signaling pathways and pulmonary angiogenesis, which plays an important role in HPS pathogenesis. At present, the most effective and only radical treatment is a liver transplant (LT). Cirrhotic patients who are on the waiting list for an LT have a shorter survival period if they develop HPS. Therefore, it is suggested that all cirrhotic cases should be followed closely for HPS and they should have priority in the waiting list.
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Abstract
Understanding the mutual relationship between the liver and the heart is important for both hepatologists and cardiologists. Hepato-cardiac diseases can be classified into heart diseases affecting the liver, liver diseases affecting the heart, and conditions affecting the heart and the liver at the same time. Differential diagnoses of liver injury are extremely important in a cardiologist’s clinical practice calling for collaboration between cardiologists and hepatologists due to the many other diseases that can affect the liver and mimic haemodynamic injury. Acute and chronic heart failure may lead to acute ischemic hepatitis or chronic congestive hepatopathy. Treatment in these cases should be directed to the primary heart disease. In patients with advanced liver disease, cirrhotic cardiomyopathy may develop including hemodynamic changes, diastolic and systolic dysfunctions, reduced cardiac performance and electrophysiological abnormalities. Cardiac evaluation is important for patients with liver diseases especially before and after liver transplantation. Liver transplantation may lead to the improvement of all cardiac changes and the reversal of cirrhotic cardiomyopathy. There are systemic diseases that may affect both the liver and the heart concomitantly including congenital, metabolic and inflammatory diseases as well as alcoholism. This review highlights these hepatocardiac diseases
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43
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Pharmacological treatment for hepatopulmonary syndrome. BIOMED RESEARCH INTERNATIONAL 2013; 2013:670139. [PMID: 24102057 PMCID: PMC3786536 DOI: 10.1155/2013/670139] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2013] [Revised: 07/30/2013] [Accepted: 08/12/2013] [Indexed: 12/12/2022]
Abstract
AIM Hepatopulmonary syndrome is a pulmonary dysfunction in the context of liver cirrhosis characterized by arterial deoxygenation. Affected patients have increased morbidity and mortality, and many of them expire before undergoing liver transplantation. Therefore, finding medical therapy as a bridge to transplantation or as a final treatment is necessary. In this study, we aimed to review the current literature about pharmacological options available for treatment of hepatopulmonary syndrome. METHODS A PubMED and Scopus search was conducted in January 2013 on the English literature published in any time period to find human and animal studies reporting pharmacological therapy of hepatopulmonary syndrome. RESULTS Out of 451 studies, 29 relevant articles were included. The number of patients, type, dose, duration, and mechanism of drugs in these studies was extracted and summarized separately. Most of pharmacologic agents act through inhibition of nitric oxide synthase and reduction in nitric oxide production, inactivation of endothelin-1, and treatment of bacterial translocation and pulmonary angiogenesis. CONCLUSION Several drugs have been applied for the treatment of HPS with conflicting results. However, no large randomized trial has been conducted probably due to low number of patients. Multicentered clinical trials are necessary to investigate these drugs.
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Garg A, Armstrong WF. Echocardiography in liver transplant candidates. JACC Cardiovasc Imaging 2013; 6:105-19. [PMID: 23328568 DOI: 10.1016/j.jcmg.2012.11.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 11/02/2012] [Accepted: 11/09/2012] [Indexed: 02/09/2023]
Abstract
Involvement of the cardiovascular system in patients with end-stage liver disease (ESLD) is well recognized and may be seen in several scenarios in adult liver transplantation (LT) candidates. The hemodynamic effects of ESLD may result in apparent heart disease, or in some instances may mask cardiac disease. Alternatively, cardiac disease can occasionally be the underlying etiology of ESLD. LT imposes significant hemodynamic stresses, with cardiovascular complications accounting for considerable perioperative mortality and morbidity. Pre-operative assessment of the cardiac status of LT candidates is thus critically important for risk stratification and management. Cardiac imaging plays an integral role in the assessment of LT candidates. In this review, we discuss the role of cardiac imaging, including transthoracic echocardiography with Doppler and contrast enhancement, noninvasive functional assessment for routine pre-operative assessment of coronary artery disease, and transesophageal echocardiography in select cases to aid in intra-operative fluid management and monitoring in LT candidates.
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Affiliation(s)
- Anubhav Garg
- Department of Internal Medicine, Division of Cardiovascular Disease, University of Michigan Medical Center, Ann Arbor, Michigan 48109-5853, USA
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45
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Ma C, Crippin JS, Chapman WC, Korenblat K, Vachharajani N, Gunter KL, Brunt EM. Parenchymal alterations in cirrhotic livers in patients with hepatopulmonary syndrome or portopulmonary hypertension. Liver Transpl 2013; 19:741-50. [PMID: 23463612 DOI: 10.1002/lt.23632] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2012] [Revised: 11/29/2012] [Accepted: 02/18/2013] [Indexed: 01/12/2023]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PPH) are distinct pulmonary vascular complications of cirrhosis. Little is known about possible associated hepatic histopathological features. Explanted livers from patients clinically diagnosed with HPS (n = 8) or PPH (n = 7) and cirrhotic explants from controls (n = 30) without HPS or PPH were evaluated with trichrome histochemistry, anti-glutamine synthetase (anti-GS), and anti-CD34 immunohistochemistry (IHC). Trichrome stains were characterized by cirrhotic nodules (CNs) of various sizes, including incomplete septal cirrhosis (ISC). ISC was overrepresented in the HPS (4/8 or 50%) and PPH livers (3/7 or 43%); in addition, neither group had micronodular cirrhosis. The control explants showed the entire spectrum of nodules: micronodular, macronodular, mixed CNs, and ISC (P = 0.04). The variability of cirrhosis severity was shown with the Laennec grading system (0-6). The cirrhosis of the majority of the HPS (6/8) and PPH livers (6/7) was scored as mild, whereas the control explants were more evenly distributed across the mild (14/30) and moderate/severe grades (16/30). GS positivity was retained in a perivenular location as the dominant pattern in each explant group. CD34 staining detected capillarized sinusoids of CNs as well as vascular channels within septa, but no significant differences were found between the groups. None of the observed light microscopy or histochemistry and IHC patterns showed a correlation with the underlying liver disease. Although our results demonstrate variable architectural and vascular remodeling within and between explant livers regardless of the presence or types of pulmonary complications, there were differences in explants with HPS or PPH versus controls that correlated with less severe cirrhosis.
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Affiliation(s)
- Changqing Ma
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
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46
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Saigal S, Choudhary N, Saraf N, Kotecha H, Kakodkar R, Mohanka R, Rastogi A, Menon P, Goja S, Govil D, Vohra V, Soin A. Excellent outcome of living donor liver transplantation in patients with hepatopulmonary syndrome: a single centre experience. Clin Transplant 2013; 27:530-4. [DOI: 10.1111/ctr.12126] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/20/2012] [Indexed: 12/15/2022]
Affiliation(s)
- Sanjiv Saigal
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Narendra Choudhary
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Neeraj Saraf
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Hardik Kotecha
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Rahul Kakodkar
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Ravi Mohanka
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Amit Rastogi
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Palat Menon
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Sanjay Goja
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
| | - Deepak Govil
- Medanta the Medicity; Institute of critical care
| | - Vijay Vohra
- Medanta the Medicity; Liver transplant anesthesia; Gurgaon; Haryana; India
| | - Arvinder Soin
- Medanta the Medicity; Institute of Liver Transplantation and Regenerative Medicine
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47
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Grace JA, Angus PW. Hepatopulmonary syndrome: update on recent advances in pathophysiology, investigation, and treatment. J Gastroenterol Hepatol 2013. [PMID: 23190201 DOI: 10.1111/jgh.12061] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatopulmonary syndrome (HPS) is an important cause of dyspnea and hypoxia in the setting of liver disease, occurring in 10-30% of patients with cirrhosis. It is due to vasodilation and angiogenesis in the pulmonary vascular bed, which leads to ventilation-perfusion mismatching, diffusion limitation to oxygen exchange, and arteriovenous shunting. There is evidence, primarily from animal studies, that vasodilation is mediated by a number of endogenous vasoactive molecules, including endothelin-1 and nitric oxide (NO). In experimental HPS, liver injury stimulates release of endothelin-1 and results in increased expression of ET(B) receptors on pulmonary endothelial cells, leading to upregulation of endothelial NO synthase (eNOS) and subsequent increased production of NO, which causes vasodilation. In addition, increased phagocytosis of bacterial endotoxin in the lung not only promotes stimulation of inducible NO synthase, which increases NO production, but also contributes to intrapulmonary accumulation of monocytes, which may stimulate angiogenesis via vascular endothelial growth factor pathway. Despite these insights into the pathogenesis of experimental HPS, there is no established medical therapy, and liver transplantation remains the main treatment for symptomatic HPS, although selected patients may benefit from other surgical or radiological interventions. In this review, we focus on recent advances in our understanding of the pathophysiology of HPS, and discuss current approaches to the investigation and treatment of this condition.
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Affiliation(s)
- Josephine A Grace
- Department of Medicine, Austin Health, The University of Melbourne, Melbourne, Victoria, Australia.
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48
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Fritz JS, Fallon MB, Kawut SM. Pulmonary vascular complications of liver disease. Am J Respir Crit Care Med 2012; 187:133-43. [PMID: 23155142 DOI: 10.1164/rccm.201209-1583ci] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary vascular complications of liver disease. The pathophysiology underlying each disorder is distinct, but patients with either condition may be limited by dyspnea. A careful evaluation of concomitant symptoms, the physical examination, pulmonary function testing and arterial blood gas analysis, and echocardiographic, imaging, and hemodynamic studies is crucial to establishing (and distinguishing) these diagnoses. Our understanding of the pathobiology, natural history, and treatment of these disorders has advanced considerably over the past decade; however, the presence of either still increases the risk of morbidity and mortality in patients with underlying liver disease. There is no effective medical treatment for hepatopulmonary syndrome. Although liver transplantation can resolve hepatopulmonary syndrome, there appears to be worse survival even with transplantation. Liver transplantation poses a very high risk of death in those with significant portopulmonary hypertension, where targeted medical therapies may improve functional status and allow successful transplantation in a small number of select patients.
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Affiliation(s)
- Jason S Fritz
- Department of Medicine, M.S., Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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49
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Abstract
Hepatopulmonary syndrome (HPS) is a serious vascular complication of liver disease that occurs in 5-32% of patients with cirrhosis. The presence of HPS markedly increases mortality. No effective medical therapies are currently available and liver transplantation is the only established treatment option for HPS. The definition and diagnosis of HPS are established by the presence of a triad of liver disease with intrapulmonary vascular dilation that causes abnormal arterial gas exchange. Experimental biliary cirrhosis induced by common bile duct ligation in the rat reproduces the pulmonary vascular and gas exchange abnormalities of human HPS and serves as a pertinent animal model. Pulmonary microvascular dilation and angiogenesis are two central pathogenic features that drive abnormal pulmonary gas exchange in experimental HPS, and thus might underlie HPS in humans. Defining the mechanisms involved in the microvascular alterations of HPS has the potential to lead to effective medical therapies. This Review focuses on the current understanding of the pathogenesis, clinical features and management of HPS.
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Affiliation(s)
- Junlan Zhang
- Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030-1501, USA
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50
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Papastergiou V, Skorda L, Lisgos P, Papakonstantinou N, Giakoumakis T, Ntousikos K, Karatapanis S. Ultrasonographic prevalence and factors predicting left ventricular diastolic dysfunction in patients with liver cirrhosis: is there a correlation between the grade of diastolic dysfunction and the grade of liver disease? ScientificWorldJournal 2012; 2012:615057. [PMID: 22888308 PMCID: PMC3410313 DOI: 10.1100/2012/615057] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2011] [Accepted: 11/20/2011] [Indexed: 02/07/2023] Open
Abstract
Presence of cardiac dysfunction has been associated with an unfavorable prognosis in patients with liver cirrhosis. In the present study, 92 consecutive, newly-diagnosed patients with liver cirrhosis were prospectively evaluated. Liver disease was graded according to the modified Child-Turcotte-Pugh (CTP) score whereas left ventricular diastolic function was assessed by Doppler-echocardiography and graded (Stage 0 to 4) according to current guidelines. Overall, DD was diagnosed in 55/92 (59.8%) patients [DD-stage-1: 36/92 (39.1%), DD-stage-2: 19/92 (20.6%)]. Prevalence of DD-stage-1 among the different stages of liver cirrhosis was: CTP-class A: 11/29 (37.9%), B: 15/39 (38.5%), C: 10/24 (41.6%), (P > 0.05 in all comparisons), whereas for DD-stage-2 the corresponding proportions were CTP-class A: 3/29 (10.3%), B: 5/39 (12.8%), C: 11/24 (45.8%), (P = 0.0009 between CTP-class C versus A and B). Age > 53 years (Odd's Ratio [OR]: 4.2; 95% confidence interval [CI]: 1.5-12.1) and CTP-class C (OR: 4.6; 95% CI: 1.1-20) could independently predict DD. No relation between presence of DD and the etiology of the liver disease was found. We conclude that DD is a common feature in liver cirrhosis. DD-stage-1 is fairly prevalent among all CTP-classes whereas DD-stage-2 seems to be characteristic of the advanced liver disease (CTP-class C). A high level of awareness for the presence of the syndrome is required, especially if cirrhotic patients are CTP-class C and/or of older age.
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Affiliation(s)
- Vasilios Papastergiou
- Liver Clinic, First Department of Internal Medicine, General Hospital of Rhodes, 85100 Rhodes, Greece
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