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Weinfurtner K, Forde K. Hepatopulmonary Syndrome and Portopulmonary Hypertension: Current Status and Implications for Liver Transplantation. CURRENT HEPATOLOGY REPORTS 2020; 19:174-185. [PMID: 32905452 PMCID: PMC7473417 DOI: 10.1007/s11901-020-00532-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
PURPOSE OF REVIEW Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (PoPH) are both pulmonary vascular complications of advanced liver disease; however, these syndromes have distinct pathophysiology, clinical implications, and management. RECENT FINDINGS While both conditions are associated with portal hypertension, HPS results from diffuse pulmonary capillary vasodilation and PoPH results from vasoconstriction and vascular remodeling of pulmonary arteries. In HPS, no medical therapies clearly improve outcomes; however, patients have excellent post-LT outcomes with near uniform reversal of hypoxemia. In PoPH, several medical therapies used in idiopathic pulmonary hypertension have been shown improve pulmonary hemodynamics, symptoms, and potentially LT outcomes; however, further study is needed to determine best treatment regimens, long-term outcomes on medical therapy, and role of LT. SUMMARY While HPS results in severe hypoxemia that is usually reversible by LT, PoPH patients develop progressive pulmonary hypertension that may improve with medical therapy.
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Affiliation(s)
- Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
| | - Kimberly Forde
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
- Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
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Yang Y, Yu H, Yang C, Zhang Y, Ai X, Wang X, Lu K, Yi B. Krüppel-like factor 6 mediates pulmonary angiogenesis in rat experimental hepatopulmonary syndrome and is aggravated by bone morphogenetic protein 9. Biol Open 2019; 8:bio.040121. [PMID: 31189661 PMCID: PMC6602319 DOI: 10.1242/bio.040121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular disease derived from chronic liver disease, and its key pathogenesis is angiogenesis. Krüppel-like factor 6 (KLF6) mediates physiological repair and remodeling during vascular injury. However, the role of KLF6 in pulmonary microvascular endothelial cells (PMVECs) during angiogenesis of HPS and its underlying mechanism in HPS have not been investigated. Common bile duct ligation (CBDL) in rats can replicate pulmonary vascular abnormalities of human HPS. Here, we found that advanced pulmonary angiogenesis and pulmonary injury score coincided with the increase of KLF6 level in PMVECs of CBDL rat; KLF6 in PMVECs was also induced while cultured with CBDL rat serum in vitro. Inhibition of KLF6 dramatically suppressed PMVEC-mediated proliferation, migration and tube formation in vivo; this may be related to the downregulation of activin receptor-like kinase-1 (ALK1) and endoglin (ENG), which are transacted by KLF6. Bone morphogenetic protein 9 (BMP9) enhanced the expression of KLF6 in PMVECs and was involved in the angiogenesis of HPS. These results suggest that KLF6 triggers PMVEC-mediated angiogenesis of HPS and is aggravated by BMP9, and the inhibition of the BMP9/KLF6 axis may be an effective strategy for HPS treatment. Summary: Krüppel-like factor 6, which is triggered by pulmonary injury and promoted by bone morphogenetic protein 9, mediates pulmonary angiogenesis in rat experimental hepatopulmonary syndrome and then aggravates lung dysfunction.
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Affiliation(s)
- Yihui Yang
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China.,Department of Anesthesia, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000 China
| | - Hongfu Yu
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China
| | - Congwen Yang
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China
| | - Yunfei Zhang
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China.,Department of Anesthesia, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000 China
| | - Xiangfa Ai
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China
| | - Xiaobo Wang
- Department of LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France
| | - Kaizhi Lu
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China
| | - Bin Yi
- Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China
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Kotera Y, Egawa H, Ogata S, Teramukai S, Kaido T, Shirabe K, Taketomi A, Takada Y, Yamamoto M, Yamaue H. Current status of hepatopulmonary syndrome in liver transplantation in Japan: a Japanese multicenter analysis. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2019; 26:292-299. [DOI: 10.1002/jhbp.632] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Affiliation(s)
- Yoshihito Kotera
- Department of Surgery Institute of Gastroenterology Tokyo Women's Medical University ShinjukuTokyo Japan
| | - Hiroto Egawa
- Department of Surgery Institute of Gastroenterology Tokyo Women's Medical University ShinjukuTokyo Japan
| | - Satoshi Ogata
- Department of Surgery Institute of Gastroenterology Tokyo Women's Medical University ShinjukuTokyo Japan
| | - Satoshi Teramukai
- Department of Biostatistics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan
| | - Toshimi Kaido
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation Kyoto University Graduate School of Medicine Kyoto Japan
| | - Ken Shirabe
- Division of Hepato‐Biliary‐Pancreatic Surgery and Transplantation Gunma University Graduate School of Medicine Gunma Japan
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I Hokkaido University Graduate School of Medicine Hokkaido Japan
| | - Yasutugu Takada
- Department of Hepato‐Biliary‐Pancreatic and Breast Surgery Ehime University Graduate School of Medicine Ehime Japan
| | - Masakazu Yamamoto
- Department of Surgery Institute of Gastroenterology Tokyo Women's Medical University ShinjukuTokyo Japan
| | - Hiroki Yamaue
- Second Department of Surgery Wakayama Medical University Wakayama Japan
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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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Grilo I, Pascasio JM, Tirado JL, López-Pardo FJ, Ortega-Ruiz F, Sousa JM, Rodríguez-Puras MJ, Ferrer MT, Gómez-Bravo MÁ, Grilo Reina A. The utility of the macro-aggregated albumin lung perfusion scan in the diagnosis and prognosis of hepatopulmonary syndrome in cirrhotic patients candidates for liver transplantation. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 109:335-343. [PMID: 28301945 DOI: 10.17235/reed.2017.4219/2016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
BACKGROUND The macro-aggregated albumin lung perfusion scan (99mTc-MAA) is a diagnostic method for hepatopulmonary syndrome (HPS). GOAL To determine the sensitivity of 99mTc-MAA in diagnosing HPS, to establish the utility of 99mTc-MAA in determining the influence of HPS on hypoxemia in patients with concomitant pulmonary disease and to determine the correlation between 99mTc-MAA values and other respiratory parameters. METHODS Data from 115 cirrhotic patients who were eligible for liver transplantation (LT) were prospectively analyzed. A transthoracic contrast echocardiography and 99mTc-MAA were performed in 85 patients, and 74 patients were diagnosed with HPS. RESULTS The overall sensitivity of 99mTc-MAA for the diagnosis of HPS was 18.9% (14/74) in all of the HPS cases and 66.7% (4/6) in the severe to very severe cases. In HPS patients who did not have lung disease, the degree of brain uptake of 99mTc-MAA was correlated with the alveolar-arterial oxygen gradient (A-a PO2) (r = 0.32, p < 0.05) and estimated oxygen shunt (r = 0.41, p < 0.05) and inversely correlated with partial pressure of arterial oxygen (PaO2) while breathing 100% O2 (r = -0.43, p < 0.05). The 99mTc-MAA was positive in 20.6% (7/36) of the patients with HPS and lung disease. The brain uptake of 99mTc-MAA was not associated with mortality and normalized in all cases six months after LT. CONCLUSIONS The 99mTc-MAA is a low sensitivity test for the diagnosis of HPS that can be useful in patients who have concomitant lung disease and in severe to very severe cases of HPS. It was not related to mortality, and brain uptake normalized after LT.
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Grilo I, Pascasio JM, López-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, Rodríguez-Puras MJ, Ferrer MT, Gómez-Bravo MÁ, Grilo A. Hepatopulmonary syndrome: which blood gas analysis criteria and position should we use for diagnosis? REVISTA ESPAÑOLA DE ENFERMEDADES DIGESTIVAS 2017; 109. [DOI: 10.17235/reed.2017.4930/2017] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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Grilo-Bensusan I, Pascasio-Acevedo JM. Hepatopulmonary syndrome: What we know and what we would like to know. World J Gastroenterol 2016; 22:5728-5741. [PMID: 27433086 PMCID: PMC4932208 DOI: 10.3748/wjg.v22.i25.5728] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2016] [Revised: 05/26/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatopulmonary syndrome (HPS) is characterized by abnormalities in blood oxygenation caused by the presence of intrapulmonary vascular dilations (IPVD) in the context of liver disease, generally at a cirrhotic stage. Knowledge about the subject is still only partial. The majority of the information about the etiopathogenesis of HPS has been obtained through experiments on animals. Reported prevalence in patients who are candidates for a liver transplantation (LT) varies between 4% and 32%, with a predominance of mild or moderate cases. Although it is generally asymptomatic it does have an impact on their quality of life and survival. The diagnosis requires taking an arterial blood gas sample of a seated patient with alveolar-arterial oxygen gradient (AaO2) ≥ 15 mm Hg, or ≥ 20 mm Hg in those over 64 years of age. The IPVD are identified through a transthoracic contrast echocardiography or a macroaggregated albumin lung perfusion scan (99mTc-MAA). There is currently no effective medical treatment. LT has been shown to reverse the syndrome and improve survival rates, even in severe cases. Therefore the policy of prioritizing LT would appear to increase survival rates. This paper takes a critical and clinical look at the current understanding of HPS, as well as the controversies surrounding it and possible future research.
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Cosarderelioglu C, Cosar AM, Gurakar M, Dagher NN, Gurakar A. Hepatopulmonary Syndrome and Liver Transplantation: A Recent Review of the Literature. J Clin Transl Hepatol 2016; 4:47-53. [PMID: 27047772 PMCID: PMC4807143 DOI: 10.14218/jcth.2015.00044] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Revised: 02/10/2016] [Accepted: 02/11/2016] [Indexed: 12/14/2022] Open
Abstract
A severe and common pulmonary vascular complication of liver disease is hepatopulmonary syndrome (HPS). It is a triad of liver dysfunction and/or portal hypertension, intrapulmonary vascular dilatations, and increased alveolar-arterial oxygen gradient. Prevalence varies according to various study groups from 4%-47%. While the most common presenting symptom of HPS is dyspnea, it is usually asymptomatic, and thus all liver transplant candidates should be screened for its presence. Pulse oximetry is a useful screening method, but arterial blood gas examination is the gold standard. If there is an abnormal P (A-a)O2 gradient, microbubble transthoracic echocardiography should be done for diagnosis. Outcome is unpredictable, and there is currently no effective medical therapy. The only effective therapy is considered to be liver transplantation. Complete resolution of HPS after liver transplantation is seen within a year in most HPS patients.
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Affiliation(s)
- Caglar Cosarderelioglu
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
| | - Arif M. Cosar
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
| | - Merve Gurakar
- Virginia Commonwealth University School of Medicine, Richmond, VA, USA
| | - Nabil N. Dagher
- Johns Hopkins University School of Medicine, Department of Surgery/Liver Transplant, Baltimore, MD, USA
| | - Ahmet Gurakar
- Johns Hopkins University School of Medicine, Department of Gastroenterology/Hepatology, Baltimore, MD, USA
- Correspondence to: Ahmet Gurakar, 720 Rutland Avenue, Ross Research Building, Suite #918, Baltimore, Maryland, 21205, USA, Tel: 410-614-3369, Fax: 410-367-2328, E-mail:
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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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Pascasio JM, Grilo I, López-Pardo FJ, Ortega-Ruiz F, Tirado JL, Sousa JM, Rodriguez-Puras MJ, Ferrer MT, Sayago M, Gómez-Bravo MA, Grilo A. Prevalence and severity of hepatopulmonary syndrome and its influence on survival in cirrhotic patients evaluated for liver transplantation. Am J Transplant 2014; 14:1391-9. [PMID: 24730359 DOI: 10.1111/ajt.12713] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2013] [Revised: 02/07/2014] [Accepted: 02/10/2014] [Indexed: 01/25/2023]
Abstract
The prevalence of hepatopulmonary syndrome (HPS) and its influence on survival before and after liver transplantation (LT) remain controversial. Additionally, the chronology of post-LT reversibility is unclear. This study prospectively analyzed 316 patients with cirrhosis who were evaluated for LT in 2002-2007; 177 underwent LT at a single reference hospital. HPS was defined by a partial pressure of arterial oxygen (PaO2 ) <70 mmHg and/or an alveolar-arterial oxygen gradient (A-a PO2 ) ≥20 mmHg in the supine position and positive contrast echocardiography. The prevalence of HPS was 25.6% (81/316 patients), and most patients (92.6%) had mild or moderate HPS. High Child-Pugh scores and the presence of ascites were independently associated with HPS. Patients with and without HPS did not significantly differ in LT waiting list survival (mean 34.6 months vs. 41.6 months, respectively; log-rank, p = 0.13) or post-LT survival (mean 45 months vs. 47.6 months, respectively; log-rank, p = 0.62). HPS was reversed in all cases within 1 year after LT. One-fourth of the patients with cirrhosis who were evaluated for LT had HPS (mostly mild to moderate); the presence of HPS did not affect LT waiting list survival. HPS was always reversed after LT, and patient prognosis did not worsen.
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Affiliation(s)
- J M Pascasio
- Digestive Diseases Department, Hospital Virgen del Rocío, Sevilla, Spain
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Abstract
The hepatopulmonary syndrome (HPS) is a pulmonary complication of cirrhosis and/or portal hypertension whereby patients develop hypoxemia as a result of alterations in pulmonary microvascular tone and architecture. HPS occurs in up to 30% of patients with cirrhosis. Although the degree of hypoxemia does not reliably correlate with the severity of liver disease, patients with HPS have a higher mortality than do patients with cirrhosis without the disorder. There has been progress into defining the mechanisms that lead to hypoxemia in HPS, but to date there are no therapeutic options for HPS aside from liver transplantation.
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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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Park TJ, Ahn KS, Kim YH, Kim H, Park UJ, Kim HT, Cho WH, Park WH, Kang KJ. Improved severe hepatopulmonary syndrome after liver transplantation in an adolescent with end-stage liver disease secondary to biliary atresia. Clin Mol Hepatol 2014; 20:76-80. [PMID: 24757662 PMCID: PMC3992334 DOI: 10.3350/cmh.2014.20.1.76] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2012] [Revised: 11/08/2012] [Accepted: 11/09/2012] [Indexed: 12/13/2022] Open
Abstract
Hepatopulmonary syndrome (HPS) is a serious complication of end-stage liver disease, which is characterized by hypoxia, intrapulmonary vascular dilatation, and liver cirrhosis. Liver transplantation (LT) is the only curative treatment modality for patients with HPS. However, morbidity and mortality after LT, especially in cases of severe HPS, remain high. This case report describes a patient with typical findings of an extracardiac pulmonary arteriovenous shunt on contrast-enhanced transesophageal echocardiography (TEE), and clubbing fingers, who had complete correction of HPS by deceased donor LT. The patient was a 16-year-old female who was born with biliary atresia and underwent porto-enterostomy on the 55th day after birth. She had been suffered from progressive liver failure with dyspnea, clubbing fingers, and cyanosis. Preoperative arterial blood gas analysis revealed severe hypoxia (arterial O2 tension of 54.5 mmHg and O2 saturation of 84.2%). Contrast-enhanced TEE revealed an extracardiac right-to-left shunt, which suggested an intrapulmonary arteriovenous shunt. The patient recovered successfully after LT, not only with respect to physical parameters but also for pychosocial activity, including school performance, during the 30-month follow-up period.
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Affiliation(s)
- Tae Jun Park
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Keun Soo Ahn
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Yong Hoon Kim
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Hyungseop Kim
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Ui Jun Park
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Hyoung Tae Kim
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Won Hyun Cho
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Woo-Hyun Park
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
| | - Koo Jeong Kang
- Department of Surgery, Keimyung University School of Medicine, Daegu, Korea
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Iyer VN, Swanson KL, Cartin-Ceba R, Dierkhising RA, Rosen CB, Heimbach JK, Wiesner RH, Krowka MJ. Hepatopulmonary syndrome: favorable outcomes in the MELD exception era. Hepatology 2013; 57:2427-35. [PMID: 22996424 DOI: 10.1002/hep.26070] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2012] [Accepted: 08/30/2012] [Indexed: 02/06/2023]
Abstract
UNLABELLED Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder occurring as a consequence of advanced liver disease, characterized by hypoxemia due to intrapulmonary vascular dilatations. HPS independently increases mortality, regardless of the cause or severity of liver disease. Liver transplantation (LT) improves survival in HPS. We present the largest consecutive series of HPS patients specifically addressing long-term survival relative to the degree of hypoxemia and the era in which LT was conducted. We evaluated 106 HPS patients at the Mayo Clinic from 1986 through 2010. Survival was assessed using Kaplan-Meier methodology. LT was accomplished in 49 HPS patients. Post-LT survival (1, 3, 5, and 10 years) did not differ between groups based on baseline partial pressure of arterial oxygen (PaO2 ) obtained at the time of HPS diagnosis. Improvements in overall survival at 1, 3, and 5 years post-LT in those HPS patients transplanted after January 1 2002 (n = 28) (92%, 88%, and 88%, respectively) as compared with those transplanted prior to that time (n = 21) (71%, 67%, and 67%, respectively) did not reach statistical significance (5-year P = 0.09). Model for Endstage Liver Disease (MELD) exception to facilitate LT was granted to 21 patients since January 1 2002 with post-LT survival of 19/21 patients and one wait-list death. CONCLUSION Long-term outcome after LT in HPS is favorable, with a trend towards improved survival in the MELD exception era since 2002 as compared to earlier HPS transplants. Survival after LT was not associated with PaO2 levels at the time of HPS diagnosis. (HEPATOLOGY 2012).
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Affiliation(s)
- Vivek N Iyer
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester,MN 55905, USA.
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Abstract
The pulmonary involvement concurrent with gastrointestinal (GI) diseases is often clinically subtle. Radiological manifestations might lag behind the respiratory compromise, and only such specialized testing as high resolution computed tomography (HRCT), permeability studies with labelled proteins, or comprehensive pulmonary function tests (PFTs) may be sensitive enough to detect the evolving pathophysiology. Increasing recognition of specific entities, such as immune-mediated alveolitis, will allow implementation of therapies that can significantly improve a patient's prognosis.
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Abstract
Hepatopulmonary syndrome (HPS) is a clinical threesome composed of liver disease, intrapulmonary vascular dilatation (IPVD) and arterial gas abnormalities. Its occurrence has been described in up to 32% of cirrhotic candidates for liver transplantation. It also affects non-cirrhotic patients with portal hypertension. Its pathogenesis is not well defined, but an association of factors such as imbalance in the endothelin receptor response, pulmonary microvascular remodeling and genetic predisposition is thought to lead to IPVD. Diagnosis is based on imaging methods that identify these dilatations, such as contrast echocardiography or perfusion scintigraphy with 99mTc, as well as analysis of arterial gases to identify elevated alveolar-arterial differences in O2 or hypoxemia. There is no effective pharmacological treatment and complete resolution only occurs through liver transplantation. The importance of diagnosing HPS lies in prioritizing transplant candidates, since presence of HPS is associated with worse prognosis. The aim of this paper was to review the pathogenetic theories and current diagnostic criteria regarding HPS, and to critically analyze the prioritization of patients with HPS on the liver transplant waiting list. Searches were carried out in the Medline (Medical Literature Analysis and Retrieval System Online) via PubMed, Cochrane Library and Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) databases for articles published between January 2002 and December 2007 involving adults and written either in English or in Portuguese, using the term hepatopulmonary syndrome. The studies of greatest relevance were included in the review, along with text books and articles cited in references that were obtained through the review.
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Deberaldini M, Arcanjo ABB, Melo E, da Silva RF, Felício HCC, Arroyo PC, Duca WJ, Cordeiro JA, da Silva RCMA. Hepatopulmonary syndrome: morbidity and survival after liver transplantation. Transplant Proc 2009; 40:3512-6. [PMID: 19100426 DOI: 10.1016/j.transproceed.2008.08.134] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2007] [Revised: 07/23/2008] [Accepted: 08/12/2008] [Indexed: 02/07/2023]
Abstract
Hepatopulmonary Syndrome (HPS) is a triad of liver disease, intrapulmonary vascular dilatation (IPVD), and arterial deoxygenation. Orthotopic liver transplantation (OLT) constitutes the only effective treatment; however, adverse outcomes have been reported. The aim of this study was to evaluate the early morbidity and short- and long-term survival after OLT for patients with and without HPS. We studied 59 transplant recipients divided into 2 groups: with HPS (HPS group n = 25) and without HPS (control group, n = 34) before the OLT. IPVD was diagnosed using transthoracic contrast-enhanced echocardiography. Arterial deoxygenation was defined as PA-a,O(2) >or= 15 mm Hg. The HPS and control groups were homogeneous regarding age (P = .36; 43.8 +/- 12.2 vs 46.9 +/- 13.5), gender (P = .47), male/female ratio (68%:32% and 78%:22%, respectively), and severity of liver disease. The PaO(2) was significantly lower (74.9 +/- 12.1 vs 93 +/- 6.4 mm Hg; P < .001) and the PA-a,O(2) was significantly higher in the HPS group (30.3 +/- 10.6 vs 11.0 +/- 7.0; P < .001). The percentage of severe (n = 3) and very severe (n = 1) hypoxemia was 16%. There were no significant differences between HPS and control groups regarding short- (68% vs 77%; P = .27) and long-term survival (60% vs 64%; P = .67) as well as among patients with mild, moderate, severe, or very severe HPS and the control group (P = .53). Also, intensive care unit (ICU) stay (7.0 vs 5.5; P = .41), duration of mechanical ventilation (38.0 vs 27.5; P = .43), reintubation rate (32.0% vs 23.5%; P = .45), and early postoperative complications (P = .72) were not different. In conclusion, there were no significant differences regarding the outcomes of OLT for patients with versus without HPS related to early morbidity or short- and long-term survival.
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Affiliation(s)
- M Deberaldini
- Department of Medicine I, Medical School of São José do Rio Preto - FAMERP, Sao Paulo, Brazil
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Sulieman BM, Hunsicker LG, Katz DA, Voigt MD. OPTN policy regarding prioritization of patients with hepatopulmonary syndrome: does it provide equitable organ allocation? Am J Transplant 2008; 8:954-64. [PMID: 18416736 DOI: 10.1111/j.1600-6143.2007.02124.x] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
United Network for Organ Transplantation (UNOS) policy 3.6.4.5.1 provides exception points to patients diagnosed with hepatopulmonary syndrome (HPS) to compensate for their reported increased mortality risk. We compared pre- and posttransplant and overall outcomes in 255 patients receiving exception points under this policy (HPS policy patients) with 32 358 nonexception control patients listed in the model for end-stage liver disease (MELD) era to determine whether the intent of the policy is being met. Overall, 92.5% of HPS policy patients versus 45.5% of controls had been transplanted, 5.1% versus 31.2% remained on waiting list and 1.5% versus 14.1% had died while awaiting transplant (p < 0.0001 for each comparison). Relative risk (RR) of death for HPS policy patients compared to controls was 0.158 (confidence interval [CI]: 0.059-0.420, p = 0.0002) pretransplant, and 0.827 (CI: 0.587-1.170, p = 0.28) posttransplant. Overall (combined waitlist and posttransplant) RR of death was 0.514 (CI: 0.374-0.707, p = 0.00004) compared with controls. After adjustment for laboratory MELD, overall RR was 0.807 (CI: 0.587-1.110, p = 0.19), indicating that HPS policy patients' mortality risk would be similar to that of controls had they been listed with their laboratory MELD score. HPS policy patients have a significant pretransplant survival advantage over standard liver transplant candidates because of the exception points awarded, and have similar posttransplant survival. Better criteria for diagnosing and grading of HPS are required.
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Affiliation(s)
- B M Sulieman
- Department of Internal Medicine, Divisions of Gastroenterology and Hepatology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
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Tumgor G, Arikan C, Yuksekkaya HA, Cakir M, Levent E, Yagci RV, Kilic M, Aydogdu S. Childhood cirrhosis, hepatopulmonary syndrome and liver transplantation. Pediatr Transplant 2008; 12:353-357. [PMID: 18435611 DOI: 10.1111/j.1399-3046.2007.00807.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVES The hepatopulmonary syndrome (HPS) is characterized as a triad: liver disease, intrapulmonary vascular dilatation, and arterial hypoxemia. The aim of this study is to analyze outcome of children with HPS in liver transplant era. METHODS Between September 1996 and November 2006, 172 cirrhotic patients (median age 5 years; range 0.2-22 years, M/F; 97/75) were followed at Ege University Pediatric Gastroenterology, Hepatology and Nutrition Unit. All patients were evaluated by chest radiography, arterial blood gas analysis, and alveolar-arterial oxygen tension difference, contrast echocardiography (CEE) after and before the liver transplantation. RESULTS HPS was diagnosed in 33 patients (19%) by CEE. None of them had pulmonary hypertension. HPS was not found related to etiology of the liver disease. Portal hypertension was found related to the development of HPS (75.7% in patients with HPS and 54.6% in others, p = 0.02). 17 of 33 patients with HPS underwent liver transplantation. Preoperative and postoperative period of these patients was uneventful. Patients were extubated in the operating room except for two. Median follow up of transplanted children was 1.9 year (range; 0.75-10 years). Arterial blood gas analysis and CEE positivity regressed in all of them by postoperative 6th month. CONCLUSIONS HPS is a serious and important complication of cirrhotic children that leads to tissue hypoxia and central cyanosis. HPS seems reversible after liver transplantation in all patients.
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Affiliation(s)
- Gokhan Tumgor
- Department of Pediatric, Division of Gastroenterology, Hepatology and Nutrition, Ege University School of Medicine Organ Transplantation and Research Center, Izmir, Turkey.
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Tumgor G, Ozkan T, Ulger Z, Kilic M, Aydogdu S. Liver transplantation of a child with child a cirrhosis and severe hepatopulmonary syndrome. Transplant Proc 2006; 38:1432-1434. [PMID: 16797324 DOI: 10.1016/j.transproceed.2006.02.106] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2005] [Indexed: 02/07/2023]
Abstract
Hepatopulmonary syndrome (HPS) is a clinical state defined by a chronic hepatic disorder, intrapulmonary vascular dilatation, and altered gas exchange resulting in hypoxemia. Cirrhosis of the liver is the most common condition associated with HPS. A 3-year-old boy who presented with end-stage liver disease and severe hepatopulmonary syndrome underwent orthotopic liver transplantation (OLT). The findings of HPS resolved immediately after OLT. His status is within normal limits at 6 months after liver transplantation.
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Affiliation(s)
- G Tumgor
- Department of Pediatric Gastroenterology/Hepatology/Nutrition and Organ Transplantation and Research Center, Ege University School of Medicine, Izmir, Turkey.
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