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1
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Panackel C, Fawaz M, Jacob M, Raja K. Pulmonary Assessment of the Liver Transplant Recipient. J Clin Exp Hepatol 2023; 13:895-911. [PMID: 37693254 PMCID: PMC10483013 DOI: 10.1016/j.jceh.2023.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 04/13/2023] [Indexed: 09/12/2023] Open
Abstract
Respiratory symptoms and hypoxemia can complicate chronic liver disease and portal hypertension. Various pulmonary disorders affecting the pleura, lung parenchyma, and pulmonary vasculature are seen in end-stage liver disease, complicating liver transplantation (LT). Approximately 8% of cirrhotic patients in an intensive care unit develop severe pulmonary problems. These disorders affect waiting list mortality and posttransplant outcomes. A thorough history, physical examination, and appropriate laboratory tests help diagnose and assess the severity to risk stratify pulmonary diseases before LT. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH) are respiratory consequences specific to cirrhosis and portal hypertension. HPS is seen in 5-30% of cirrhosis cases and is characterized by impaired oxygenation due to intrapulmonary vascular dilatations and arteriovenous shunts. Severe HPS is an indication of LT. The majority of patients with HPS resolve their hypoxemia after LT. When pulmonary arterial hypertension occurs in patients with portal hypertension, it is called POPH. All other causes of pulmonary arterial hypertension should be ruled out before labeling as POPH. Since severe POPH (mean pulmonary artery pressure [mPAP] >50 mm Hg) is a relative contraindication for LT, it is crucial to screen for POPH before LT. Those with moderate POPH (mPAP >35 mm Hg), who improve with medical therapy, will benefit from LT. A transudative pleural effusion called hepatic hydrothorax (HH) is seen in 5-10% of people with cirrhosis. Refractory cases of HH benefit from LT. In recent years, increasing clinical expertise and advances in the medical field have resulted in better outcomes in patients with moderate to severe pulmonary disorders, who undergo LT.
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Affiliation(s)
| | - Mohammed Fawaz
- Integrated Liver Care, Aster Medcity, Kochi, Kerala, India
| | - Mathew Jacob
- Integrated Liver Care, Aster Medcity, Kochi, Kerala, India
| | - Kaiser Raja
- King's College Hospital London, Dubai Hills, Dubai, United Arab Emirates
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2
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Abstract
The most common pulmonary complications of chronic liver disease are hepatic hydrothorax, hepatopulmonary syndrome, and portopulmonary hypertension. Hepatic hydrothorax is a transudative pleural effusion in a patient with cirrhosis and no evidence of underlying cardiopulmonary disease. Hepatic hydrothorax develops owing to the movement of ascitic fluid into the pleural space. Hepatopulmonary syndrome and portopulmonary hypertension are pathologically linked by the presence of portal hypertension; however, their pathophysiologic mechanisms are significantly different. Hepatopulmonary syndrome is characterized by low pulmonary vascular resistance secondary to intrapulmonary vascular dilatations and hypoxemia; portopulmonary hypertension features elevated pulmonary vascular resistance and constriction/obstruction within the pulmonary vasculature.
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Affiliation(s)
- Rodrigo Cartin-Ceba
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Arizona, 13400 East Shea Boulevard, Scottsdale, AZ 85259, USA.
| | - Michael J Krowka
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic Rochester, 200 1st Street SW, Rochester, MN 55905, USA
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3
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Rodríguez-Almendros N, Toapanta-Yanchapaxi LN, Aguirre Valadez J, Espinola Zavaleta N, Muñoz-Martínez SG, García-Juárez I. [Portopulmonary hypertension: Updated review]. ARCHIVOS DE CARDIOLOGIA DE MEXICO 2016; 88:25-38. [PMID: 27986561 DOI: 10.1016/j.acmx.2016.11.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2016] [Revised: 11/08/2016] [Accepted: 11/08/2016] [Indexed: 11/19/2022] Open
Abstract
Portopulmonary hypertension (PPH) is a rare condition worldwide, although epidemiological data are unknown in Mexico. However, chronic liver diseases are very prevalent in Mexico. PPH is the 4th subtype in frequency in the group of pulmonary arterial hypertension. Its diagnosis is made within 2 scenarios: patients with suspected pulmonary hypertension and candidates for orthotopic liver transplantation (OLT). Both echocardiogram and a right cardiac catheterisation are crucial for diagnosis in both cases. PPH is a challenge for OLT, since it can significantly increase perioperative mortality. The use of specific therapy is the cornerstone of this disease, as a measure to improve the outcome of those who become candidates for OLT with moderate to severe PPH. It is important to recognise that PPH can be a contraindication to OLT. The role of lung-liver transplantation or heart-lung-liver transplantation as a measure to heal pulmonary vascular disease in patients with PPH is still uncertain.
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Affiliation(s)
- Nielzer Rodríguez-Almendros
- Departamento de Hipertensión Pulmonar y Función Ventricular Derecha, UMAE Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México, D.F., México
| | - Liz N Toapanta-Yanchapaxi
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Jonathan Aguirre Valadez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Nilda Espinola Zavaleta
- Departamento de Ecocardiografia, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de México, México
| | - Sergio G Muñoz-Martínez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México
| | - Ignacio García-Juárez
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México.
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Bozbas SS, Bozbas H. Portopulmonary hypertension in liver transplant candidates. World J Gastroenterol 2016; 22:2024-2029. [PMID: 26877607 PMCID: PMC4726675 DOI: 10.3748/wjg.v22.i6.2024] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 10/21/2015] [Accepted: 12/21/2015] [Indexed: 02/06/2023] Open
Abstract
Pulmonary vascular disorders including portopulmonary hypertension (PoPHT) are among the common complications of liver disease and are prognostically significant. Survival is very low without medical treatment and liver transplantation. With advances in medical therapy for elevated pulmonary artery pressure (PAP) and liver transplant surgery, survival of patients with PoPHT and advanced liver disease is significantly improved. Because of the prognostic significance of PoPHT and the limited donor pool, a comprehensive preoperative cardio-pulmonary assessment is of great importance in cirrhotic patients prior to transplant surgery. Therefore, a detailed transthoracic Doppler echocardiographic examination must be an essential component of this evaluation. Patients with mild PoPHT can safely undergo liver transplant surgery. In cases of moderate to severe PoPHT, right heart catheterization (RHC) should be performed. In patients with moderate to severe PoPHT on RHC (mean PAP 35-45 mmHg), vasodilator therapy should be attempted. Liver transplantation should be encouraged in cases that demonstrate a positive response. Bridging therapy with specific pulmonary arterial hypertension treatment agents should be considered until the transplant surgery and should be continued during the peri- and post-operative periods as needed.
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5
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Fussner LA, Iyer VN, Cartin-Ceba R, Lin G, Watt KD, Krowka MJ. Intrapulmonary vascular dilatations are common in portopulmonary hypertension and may be associated with decreased survival. Liver Transpl 2015; 21:1355-64. [PMID: 26077312 DOI: 10.1002/lt.24198] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 06/01/2015] [Accepted: 06/11/2015] [Indexed: 12/17/2022]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are pulmonary vascular complications of portal hypertension with divergent clinicopathologic features and management. The presence of intrapulmonary vascular dilatations (IPVDs), detected by agitated saline contrast-enhanced transthoracic echocardiography (cTTE), is an essential feature of HPS but is not typically characteristic of POPH. Although IPVDs have been reported rarely in POPH, the prevalence and significance of this finding have not been systematically studied. We conducted a retrospective chart review of 80 consecutive patients diagnosed with POPH from January 1, 2002 to June 30, 2014 with documentation of cTTE findings, pulmonary hemodynamics, oxygenation, and survival. A total of 34 of the 80 patients (42%) underwent cTTE during initial diagnosis of POPH. IPVDs were detected in 20/34 patients (59%); intracardiac shunting was detected in 9/34 patients (26%; 4 also had IPVDs); and 9 patients (26%) had negative cTTE with no evidence of IPVD or intracardiac shunting. Patients with IPVD had decreased survival as compared to those without IPVD (P = 0.003), a trend that persisted after exclusion of liver transplant recipients (P = 0.07). The IPVD group had a trend toward higher Model for End-Stage Liver Disease score with and without incorporating sodium (MELD or MELD-Na; P = 0.05 for both). The right ventricular index of myocardial performance (RIMP) was lower in the IPVD group (median, 0.4 versus 0.6; P = 0.006). Patients with moderate or large IPVDs (n = 6) had worse oxygenation parameters (partial pressure of arterial oxygen, diffusing capacity of the lung for carbon monoxide, and alveolar-arterial oxygen gradient) as compared to the rest of the cohort. Unexpectedly, IPVDs were frequently documented in POPH and associated with decreased survival. To further understand this observation, we recommend screening for IVPD in all patients with POPH.
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Affiliation(s)
| | - Vivek N Iyer
- Divisions of Pulmonary and Critical Care Medicine
| | | | - Grace Lin
- Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
| | - Kymberly D Watt
- Divisions of Gastroenterology and Hepatology, Mayo Clinic Transplant Center, Rochester, Minnesota
| | - Michael J Krowka
- Divisions of Pulmonary and Critical Care Medicine.,Divisions of Gastroenterology and Hepatology, Mayo Clinic Transplant Center, Rochester, Minnesota
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Feltracco P, Serra E, Brezzi ML, Milevoj M, Rizzi S, Furnari M, Barbieri S, Salvaterra F, Ori C. Hemodynamic profile of portopulmonary hypertension. Transplant Proc 2015; 41:1235-9. [PMID: 19460527 DOI: 10.1016/j.transproceed.2009.02.058] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Portopulmonary hypertension (PPHTN) refers to the development of pulmonary arterial hypertension in the setting of portal hypertension with or without chronic hepatic failure. This syndrome is characterized by marked alternations of pulmonary vascular tone and obstruction of pulmonary arterial blood flow. An increased pulmonary blood flow, which is a hallmark of the hyperdynamic circulation of cirrhotic patients, seems to be present in almost all patients who develop PPHTN. The elevations of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) along with the transpulmonary gradient (TPG) have been considered in diagnosing PPHTN. Only a high TPG reflects the severity of obstruction to pulmonary blood flow and differentiates an elevated PAP with concomitant elevated PVR from the situation where the increase in PAP is due only to the hyperdynamic flow and elevated volume. A considerable risk for cardiovascular death arises when PAP increases significantly; this may occur in rapidly evolving syndromes, in very advanced disease, or during a complicated liver transplantation. The distinction between PPHTN and elevated PAP in the context of a hyperdynamic state is of great importance; a PAP increase of hyperkinetic origin, as opposed to PPHTN, is apparently not associated with a high risk for adverse effects during and following liver transplantation.
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Affiliation(s)
- P Feltracco
- Department of Pharmacology, University Hospital of Padua, Padua, Italy.
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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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8
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Restrepo R, Singer EF, Baram M, Restrepo R, Singer EF, Baram M. Hepatopulmonary syndrome and portopulmonary hypertension. Hosp Pract (1995) 2013; 41:62-71. [PMID: 23680738 DOI: 10.3810/hp.2013.04.1049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Hepatopulmonary syndrome and portopulmonary hypertension are 2 of many diseases that affect the lungs in patients with liver disease. The 2 vascular conditions are often confused. We review both hepatopulmonary syndrome and portopulmonary hypertension to better understand their pathophysiologies, clinical presentations, tools to aid in differentiating and diagnosing the disease states, treatment options, and influences on patient prognosis. We also consider patient viability for liver transplantation.
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Affiliation(s)
- Ricardo Restrepo
- Department of Medicine, Division of Pulmonary Critical Care Medicine, Thomas Jefferson University, Philadelphia, PA, USA
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9
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Raevens S, Colle I, Reyntjens K, Geerts A, Berrevoet F, Rogiers X, Troisi RI, Van Vlierberghe H, De Pauw M. Echocardiography for the detection of portopulmonary hypertension in liver transplant candidates: an analysis of cutoff values. Liver Transpl 2013; 19:602-10. [PMID: 23584902 DOI: 10.1002/lt.23649] [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] [Received: 11/11/2012] [Accepted: 02/27/2013] [Indexed: 12/12/2022]
Abstract
Portopulmonary hypertension (POPH), a complication of chronic liver disease, may be a contraindication to liver transplantation (LT) because of the elevated risk of peritransplant and posttransplant morbidity and mortality. Because POPH is frequently asymptomatic, screening with echocardiography is recommended. The only reliable technique, however, for diagnosing POPH is right heart catheterization (RHC). The aims of this study were to evaluate the current estimated systolic pulmonary artery pressure (sPAP) cutoff value of 30 mm Hg and to determine a better cutoff value. One hundred fifty-two patients underwent pretransplant echocardiography between January 2005 and December 2010. These echocardiographic results were compared with pulmonary artery pressures measured during the pretransplant workup or at the beginning of the transplantation procedure (both by catheterization). With a cutoff value of 30 mm Hg, 74 of the 152 patients met the criteria for POPH on echocardiography, although the diagnosis was confirmed in only 7 patients during catheterization; this resulted in a specificity of 54%. It would have been more accurate to use a cutoff value of 38 mm Hg, which had a maximal specificity of 82% and, at the same time, guaranteed a sensitivity and negative predictive value of 100%. With the incorporation of the presence or absence of right ventricular dilatation, the specificity even increased to 93% for this new cutoff value. In conclusion, the prevalence of POPH was 4.6% among LT candidates in this study. We can recommend that LT candidates with an sPAP > 38 mm Hg should be referred for RHC. With the cutoff value increased from 30 to 38 mm Hg, the number of patients undergoing invasive RHC during their evaluation could be safely reduced.
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Affiliation(s)
- Sarah Raevens
- Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium
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Chen HS, Xing SR, Xu WG, Yang F, Qi XL, Wang LEM, Yang CQ. Portopulmonary hypertension in cirrhotic patients: Prevalence, clinical features and risk factors. Exp Ther Med 2013; 5:819-824. [PMID: 23403613 PMCID: PMC3570126 DOI: 10.3892/etm.2013.918] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Accepted: 01/11/2013] [Indexed: 12/25/2022] Open
Abstract
The incidence and clinical features of portopulmonary hypertension (POPH) have not been adequately described and it is currently unknown whether an association exists between the severity of POPH and liver function. Additionally, POPH risk factors are yet to be identified. The aim of this study was to determine the prevalence, describe the clinical features and investigate the potential risk factors of POPH. We conducted a study of 100 cirrhotic patients hospitalized between March 2011 and May 2012 at Tongji Hospital in Shanghai. The clinical characteristics of patients with and without POPH were analyzed. Clinical variables with a possible association with POPH were measured and pulmonary artery systolic pressure (PASP) was determined by cardiac Doppler echocardiography. Of the 100 patients enrolled in this study, 10 were diagnosed with POPH. Seven of the cases were mild, two were moderate and only one was severe; eight were attributed to viral infections. POPH was not detected in patients with schistosomal or alcoholic cirrhosis. Hemoglobin (Hb) levels were lower in patients with POPH compared to those without POPH (P<0.01) and the severity of POPH was not significantly correlated with Child-Pugh grade (R=−0.06, P=0.09). Hb levels, incidence of hepatitis C virus (HCV) infection and portal vein thrombosis differed between the two groups (P<0.05). Hb levels were identified as an independent risk factor associated with POPH and portal vein thrombosis may play an important role during the development of POPH. However, the severity of POPH was not associated with liver function.
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Affiliation(s)
- Hui-Song Chen
- Division of Gastroenterology and Digestive Diseases Institute, Tongji Hospital of Tongji University School of Medicine, Shanghai 200065, P.R. China
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Abstract
Portopulmonary hypertension (POPH) is a serious complication of cirrhosis that is associated with mortality beyond that predicted by the Model for End-Stage Liver Disease (MELD) score. Increased pulmonary vascular resistance (PVR) may be initiated by pulmonary vasoconstriction, altered levels of circulating mediators, or shear stress, and can eventually lead to the classic vascular remodeling (plexiform lesion) that characterizes POPH. Portal hypertension is a prerequisite for the diagnosis of POPH, although the severity of pulmonary hypertension is unrelated to the severity of portal hypertension or the nature or severity of liver disease. POPH precludes liver transplantation (LT) unless the mean pulmonary artery pressure (MPAP) can be reduced to a safe level. The concept of an acceptable pressure has changed: we now consider both MPAP and PVR in the diagnosis, and we include the transpulmonary pressure gradient so that we can factor in fluid overload and left ventricular failure. Pulmonary vasodilator therapy includes oral, inhaled, and parenteral agents, and one or more of these agents may significantly lower pulmonary artery pressures to the point that LT becomes possible. The United Network for Organ Sharing recommends MELD exception points for patients with medically controlled POPH, but this varies by region. Patients who undergo LT need specialized intraoperative and postoperative management, which includes the availability of intraoperative transesophageal echocardiography for assessing right ventricular function, and rapidly acting vasodilators (eg, inhaled nitric oxide and/or epoprostenol). Published case series suggest excellent outcomes after LT for patients who respond to medical therapy.
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12
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Kalambokis GN, Mouzaki A, Rodi M, Pappas K, Korantzopoulos P, Tsianos EV. Circulating endotoxin and interleukin-6 levels are associated with Doppler-evaluated pulmonary vascular resistance in cirrhotic patients. Hepatol Int 2012. [PMID: 26201526 DOI: 10.1007/s12072-011-9337-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
PURPOSE Endotoxin and interleukin-6 levels (IL-6) have been involved in the development of pulmonary hypertension (PH) in non-cirrhotic experimental models and subjects. High circulating levels of both substances have been detected in cirrhosis. The association between circulating endotoxin and IL-6 levels and echocardiographically evaluated pulmonary vascular resistance (PVR) in cirrhotic patients are investigated. METHODS Thirty-seven cirrhotic patients were studied: 25 with PVR <120 dynes s cm(-5) (group 1) and 12 with PVR >120 dynes s cm(-5) (group 2). Plasma endotoxin and serum IL-6 levels were measured. The PVR and cardiac output (CO) by Doppler ultrasound, mean arterial pressure (MAP), and systemic vascular resistance (SVR) as the ratio MAP/CO were evaluated. RESULTS Child-Pugh scores, MAP, CO, and SVR were similar in both groups. Endotoxin levels were correlated significantly with IL-6 levels (r = 0.342; P = 0.03). Endotoxin and IL-6 levels were significantly higher in group 2 compared to group 1 (2.26 [0.39-8.4] vs. 0.85 [0.37-7.6] EU/mL; P = 0.04 and 37.4 [7.85-106.5] vs. 8.36 [3.15-53.7] pg/mL; P < 0.001, respectively). The PVR was correlated significantly with endotoxin levels in group 2 (r = 0.587; P = 0.04) and with IL-6 levels in group 1 (r = 0.529; P = 0.01) and group 2 (r = 0.760; P = 0.004), respectively. CONCLUSIONS Our results suggest that endotoxin and IL-6 may contribute to cirrhosis-associated PH. In this regard, modulation of these substances could improve pulmonary pressures in cirrhotic patients.
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Affiliation(s)
- Georgios N Kalambokis
- First Division of Internal Medicine and Hepato-Gastroenterology Unit, Medical School of Ioannina, University Hospital, 45110, Ioannina, Greece.
| | - Athanasia Mouzaki
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | - Maria Rodi
- Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece
| | | | | | - Epameinondas V Tsianos
- First Division of Internal Medicine and Hepato-Gastroenterology Unit, Medical School of Ioannina, University Hospital, 45110, Ioannina, Greece.
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Agarwal R, Gomberg-Maitland M. Current therapeutics and practical management strategies for pulmonary arterial hypertension. Am Heart J 2011; 162:201-13. [PMID: 21835279 DOI: 10.1016/j.ahj.2011.05.012] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2011] [Accepted: 05/03/2011] [Indexed: 10/18/2022]
Abstract
Pulmonary arterial hypertension (PAH) develops from an abnormal interaction between the endothelium and smooth muscle cells in the pulmonary vasculature and is characterized by a progressive rise in pulmonary vascular resistance resulting from vascular remodeling, vasoconstriction, and cellular proliferation. Currently, 3 classes of drugs are approved for the treatment of PAH based on results from small short-term clinical trials-prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors. The pharmacologic management of PAH is rapidly evolving as newer therapeutic targets that stabilize or reverse pulmonary vascular disease and target right ventricular function are being sought and as clinical practice patterns shift in favor of earlier diagnosis and aggressive treatment. This manuscript will review the practical management aspects of currently approved PAH treatments and briefly discuss combination therapy and novel pharmacologic targets. In addition, the treatment of acute right ventricular failure and evidence (or lack thereof) for therapies in non-PAH pulmonary hypertension, such as pulmonary hypertension from left side of the heart disease, are addressed.
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14
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Kalambokis GN, Pappas K, Tsianos EV. Differential effects of terlipressin on pulmonary and systemic hemodynamics in patients with cirrhosis and pulmonary hypertension: an echo study. Angiology 2011; 63:199-205. [PMID: 21733953 DOI: 10.1177/0003319711411704] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Terlipressin has been associated with pulmonary arterial vasodilation in patients with pulmonary hypertension (PH). We investigated the effects of terlipressin on pulmonary vascular resistance (PVR) in patients with cirrhosis without and with PH. Pulmonary vascular resistance and cardiac output (CO) by Doppler ultrasound, mean arterial pressure (MAP), and systemic vascular resistance (SVR) were evaluated in patients with cirrhosis with PVR -120 dyne s cm⁻⁵ (group 1, n = 20) and PVR >120 dyne s cm⁻⁵ (group 2, n = 10) before and 30 minutes after terlipressin infusion (2 mg). After terlipressin, PVR increased significantly in group 1 (96.1 ± 20.2 vs 85.1 ± 18 dyne s cm⁻⁵; P = .004) but decreased significantly in group 2 (170.4 ± 37.8 vs 157.8 ± 28.1 dyne s cm⁻⁵; P= .04). Pulmonary vascular resistance changes in group 2 correlated significantly with baseline PVR (r = -0.632; P = .04). Terlipressin induced a significant increase in MAP and SVR and a significant decrease in CO in both groups. Terlipressin significantly reduces pulmonary pressures in patients with cirrhosis having PH together with systemic hemodynamic improvement.
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Affiliation(s)
- Georgios N Kalambokis
- 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece
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15
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Kalambokis GN, Fotopoulos A, Pappas K, Tsianos EV. Renal Function Impairment in Patients With Cirrhosis Having Pulmonary Hypertension. Angiology 2011; 62:585-7. [DOI: 10.1177/0003319711399417] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Georgios N. Kalambokis
- 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece
| | | | | | - Epameinondas V. Tsianos
- 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, University Hospital, Ioannina, Greece
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16
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Kalambokis GN, Mouzaki A, Rodi M, Pappas K, Korantzopoulos P, Tsianos EV. Serum interleukin 6 levels and cirrhosis-associated pulmonary hypertension. Angiology 2011; 62:344-5. [PMID: 21421621 DOI: 10.1177/0003319710396352] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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17
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Kim C, Park YB. Pharmacotherapy for pulmonary arterial hypertension. JOURNAL OF THE KOREAN MEDICAL ASSOCIATION 2011. [DOI: 10.5124/jkma.2011.54.12.1299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Changhwan Kim
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
- Lung Research Institute, Hallym University College of Medicine, Seoul, Korea
| | - Yong Bum Park
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea
- Lung Research Institute, Hallym University College of Medicine, Seoul, Korea
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Herzer K, Post F, Canbay A, Gerken G. [Pulmonary affection in advanced liver disease - hepatepulonary syndrome and portopulmonary hypertension]. MEDIZINISCHE KLINIK (MUNICH, GERMANY : 1983) 2010; 105:916-923. [PMID: 21240591 DOI: 10.1007/s00063-010-1157-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/11/2010] [Accepted: 10/25/2010] [Indexed: 05/30/2023]
Abstract
Patients suffering from severe chronic liver disease, in particular cirrhosis, are at risk for pulmonary complications. The leading clinical symptom is shortness of breath, which can accompany the actual disease as indirect effect because of anemia, faint muscles or ascites. On the other hand, dyspnea can have multiple additive causes in case of accompanying cardial or pulmonary disease. The hepatopulmonary syndrome (HPS) and the portopulmonary hypertension (PoPH) belong to the most relevant pulmonary complications in liver cirrhosis. HPS appears to be more common than PoPH and the presence of either entity increases morbidity and mortality in patients with liver disease. The two diseases have to be strictly distinguished, as they have opposed histological and pathophysiological origin. While the HPS is a dilatative pulmonary- vascular disease, the PoPH is a constrictive or obliterative pulmonary-vascular disease in the context of a liver disease or a portal hypertension. Therefore, these diseases are separate entities also when it comes to diagnostics and therapy.
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Affiliation(s)
- Kerstin Herzer
- Zentrum für Innere Medizin, Gastroenterologie und Hepatologie, Essen, Germany.
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Kalambokis GN, Pappas K, Tsianos EV. Effect of alpha1-blockade with doxazosin in pulmonary hypertension associated with cirrhosis. Scand J Gastroenterol 2010; 45:1135-6. [PMID: 20632812 DOI: 10.3109/00365521.2010.490951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Cartin-Ceba R, Swanson K, Iyer V, Wiesner RH, Krowka MJ. Safety and efficacy of ambrisentan for the treatment of portopulmonary hypertension. Chest 2010; 139:109-14. [PMID: 20705798 DOI: 10.1378/chest.10-0574] [Citation(s) in RCA: 87] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Ambrisentan is a selective endothelin-receptor antagonist that is approved by the US Food and Drug Administration for the treatment of pulmonary arterial hypertension. We describe hemodynamic responses and clinical outcomes of patients with portopulmonary hypertension (POPH) treated with ambrisentan. METHODS In this observational study, we prospectively identified and followed consecutive adult patients with POPH who received monotherapy with ambrisentan ≤ 10 mg daily from January 2007 until December 2009. Liver enzymes were assessed monthly. Pulmonary hemodynamic responses were assessed using echocardiograms and right-sided heart catheterizations. RESULTS We identified 13 patients (seven men) with POPH and began monotherapy with ambrisentan. The median age was 57 (interquartile range [IQR], 52-60). Patients were followed for a median of 613 days (IQR, 385-1,011). The median model for end-stage liver disease score was 10 (IQR, 8.5-15); eight patients had Child-Turcotte-Pugh A classification. Median time on ambrisentan therapy was 390 days (IQR, 363-611). Two patients died, one of advanced hepatocellular carcinoma and one of septic shock following pneumonia. The mean pulmonary artery pressure decreased from a baseline median of 58 mm Hg (IQR, 37-63) to 41 mm Hg (IQR, 27-48) (P = .004). The pulmonary vascular resistance median was reduced from 445 dynes/s/cm(5) (IQR, 329-834) to 174 dynes/s/cm(5) (IQR, 121-361) (P = .008). There was no difference in the longitudinal analysis of liver function tests (aspartate aminotransferase, alanine aminotransferase, total bilirubin, and international normalized ratio) after 12 months of therapy. One patient underwent successful liver transplantation and normalized pulmonary hemodynamic responses after transplantation. CONCLUSIONS In this small cohort of patients with moderate to severe pulmonary hypertension in the setting of POPH, we have shown that ambrisentan monotherapy can significantly improve pulmonary hemodynamic responses without adverse effect on hepatic function.
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Affiliation(s)
- Rodrigo Cartin-Ceba
- Department of Medicine, the Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA.
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Coexisting hepatopulmonary syndrome and portopulmonary hypertension: implications for liver transplantation. J Clin Gastroenterol 2010; 44:e136-40. [PMID: 20463591 DOI: 10.1097/mcg.0b013e3181da76fc] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) represent pulmonary complications of liver disease and portal hypertension. The underlying pathophysiology behind these entities is complex and involves different effects of vasoactive substances on the pulmonary vasculature, among them endothelin-1 and nitric oxide (NO). Hepatopulmonary syndrome results from vasodilation, intrapulmonary shunting, and hypoxia. In contrast, portopulmonary hypertension is predominantly owing to generalized vasoconstriction that leads to remodeling and an increase in pulmonary vascular resistance, but is rarely associated with hypoxia. We present a case report in which these 2 processes with opposing pathologic mechanisms coexist in the same patient. We also conducted a literature search to identify other documented cases of coexisting hepatopulmonary syndrome and portopulmonary hypertension, common clinical features of these patients, and outcomes with or without treatment. Our case highlights the importance of recognizing the coexistence of these 2 disease processes, as they may occur simultaneously and affect the approach to treatment, including liver transplantation.
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Spagnolo P, Zeuzem S, Richeldi L, du Bois RM. The complex interrelationships between chronic lung and liver disease: a review. J Viral Hepat 2010; 17:381-90. [PMID: 20384964 DOI: 10.1111/j.1365-2893.2010.01307.x] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Lung complications may occur as a result of hepatic disease from any cause and represent a highly heterogeneous group of conditions. Early recognition of such complications may be challenging but is crucial both in forming a meaningful differential diagnosis and in avoiding severe sequelae and irreversible damage. Although a number of different pathogenetic mechanisms are likely to be involved, chronic liver dysfunction may cause pulmonary manifestations because of alterations in the production or clearance of circulating cytokines and other mediators. This is likely to be the case in hepatopulmonary syndrome, portopulmonary hypertension and primary biliary cirrhosis, although their pathogenesis remains largely speculative. Moreover, the severity of lung manifestations may or may not correspond to that of liver impairment, making disease outcome often unpredictable. Congenital and inflammatory disorders, however, may primarily affect both the liver and lung. Apart from specific diseases, a number of medications can also result in pulmonary and hepatic toxic effects. This is particularly important with cytokine therapy - used to treat viral hepatitis, among other diseases - because treatment consists of drug discontinuation, which, in turn, may cause reactivation or progression of the underlying disease that the drug was used for. This review summarizes salient diagnostic and therapeutic aspects of these often misdiagnosed conditions and highlights, based on the most recent literature, the need for early referral of such patients to centres with specific expertise in the field. In fact, a multidisciplinary approach involving pulmonologists, hepatologists and, in particularly severe cases, transplant surgeons has been already proven successful.
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Affiliation(s)
- P Spagnolo
- Center for Rare Lung Diseases, Department of Oncology, Haematology, and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy.
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Abstract
Portopulmonary hypertension (PoPH) is an underrecognized complication of portal hypertension, related to cirrhosis and noncirrhotic portal hypertension. PoPH has been found in 5-6% of patients with decompensated liver disease and may adversely affect outcome after liver transplantation. The prevalence of PoPH is unrelated to the severity of liver disease but associated with female sex and underlying autoimmune liver disease. Diagnosis of PoPH is based on screening with Doppler echocardiography and confirmation by right-heart catheterization. Treatment options with proven efficacy in idiopathic pulmonary hypertension include endothelin receptor antagonists, prostanoids, and sildenafil. In PoPH, such targeted treatment was found to be safe in small uncontrolled studies but randomized trials demonstrating its benefit are lacking.
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Abstract
BACKGROUND Endothelin receptor antagonists (ERAs) have recently become prominent therapies for pulmonary arterial hypertension, and are being explored clinically in several areas, including resistant hypertension, idiopathic pulmonary fibrosis, and cancer. OBJECTIVE To review the available preclinical and clinical data surrounding ERAs and their potential role to treat portal hypertension. METHODS A systematic search of peer-reviewed publications was performed using PubMed and Ovid/Medline/EMBASE databases. RESULTS Several preclinical in vivo studies have evaluated ERAs in models of portal hypertension. The majority of these studies employ nonselective ERAs, and support the hypothesis that endothelin participates in the development and maintenance of portal hypertension. A limited number of studies have addressed whether ET(A) receptor-selective ERAs provide an advantage over nonselective agents in ameliorating the effects of portal hypertension, and the majority of these data indicate that selective ERAs may be sufficient. Very few clinical studies have evaluated ERAs in portal hypertension patients. What has been described in humans supports a role for endothelin, but is not sufficient to draw conclusions regarding ERA selectivity. CONCLUSION While preclinical evidence suggests a role for endothelin and ERAs in portal hypertension, scant and equivocal clinical data highlight a need for human studies with current selective and nonselective ERAs.
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Affiliation(s)
- Kelly R Pitts
- Gilead Sciences Inc., In Vitro Biology, 7575 West 103rd Avenue, Westminster, Colorado 80021, USA.
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Yeshua H, Blendis LM, Oren R. Pulmonary manifestations of liver diseases. Semin Cardiothorac Vasc Anesth 2009; 13:60-9. [PMID: 19336439 DOI: 10.1177/1089253209334615] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Respiratory problems are common in patients with chronic liver diseases. The most common causes are disorders that are not related to liver diseases such as asthma and COPD. In addition certain liver diseases that are associated with specific pulmonary abnormalities, and conditions associated with end stage liver disease like tense ascites and intercostal muscular wasting are considered. Finally two unique disorders characterizing by vascular abnormalities independent of cardiorespiratory disorder-the hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are observed. These disorders have different pathogenesis, different clinical pictures, treatment and prognosis. This article reviews the epidemiology, pathophysiology, clinical features, evaluation and current therapy of these two disorders.
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Affiliation(s)
- Hanny Yeshua
- Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Clalit Health Services, and the Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel
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Nakamura K, Fujio H. Are Adrenergic Receptor Blockers Effective or Contraindicated in Pulmonary Arterial Hypertension? Circ J 2009; 73:2212-3. [DOI: 10.1253/circj.cj-09-0807] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Kazufumi Nakamura
- Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
| | - Hideki Fujio
- Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital
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Kalambokis G, Korantzopoulos P, Nikas SA, Theodorou A, Tsianos EV. Significant improvement of portopulmonary hypertension after 1-week terlipressin treatment. J Hepatol 2008; 48:678-80. [PMID: 18280605 DOI: 10.1016/j.jhep.2007.12.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2007] [Revised: 11/25/2007] [Accepted: 12/06/2007] [Indexed: 12/04/2022]
Abstract
Cirrhosis associated with moderate and severe portopulmonary hypertension carries a poor prognosis. Optimal management has not yet been defined. Current treatment options, such as prostacyclin analogues, endothelin antagonists, and phosphodiesterase-5 inhibitors, are characterized by slow onset of action and various adverse effects, particularly in patients with advanced cirrhosis. Here, we report the significant reduction of pulmonary arterial pressure after 1-week terlipressin treatment in a patient with concomitant hepato-renal syndrome. Terlipressin could be a novel and safe treatment for portopulmonary hypertension.
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Affiliation(s)
- Georgios Kalambokis
- 1st Division of Internal Medicine, University of Ioannina, Medical School, 45110 Ioannina, Greece
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Steinbis S. Portopulmonary Hypertension and Liver Transplantation: What Does it Mean for Your Patient? J Nurse Pract 2008. [DOI: 10.1016/j.nurpra.2007.10.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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Liver transplantation and pulmonary hypertension: pathophysiology and management strategies. Curr Opin Organ Transplant 2007; 12:274-280. [DOI: 10.1097/mot.0b013e32814a599c] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Abstract
As a result of the success of orthotopic liver transplantation, there has been increasing interest in the diagnosis and therapeutic options for the pulmonary vascular complications of hepatic disease. These pulmonary vascular complications range from the hepatopulmonary syndrome, which is characterized by intrapulmonary vascular dilatations, to portopulmonary hypertension (POPH), which is characterized by an elevated pulmonary vascular resistance as a consequence of obstruction to pulmonary arterial blood flow. This review concentrates on POPH.
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Affiliation(s)
- Jason M Golbin
- Division of Pulmonary and Critical Care Medicine, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA
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