Hepatopulmonary Syndrome In Patients Research Articles

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation

Background and AimsConsiderate patient selection is vital to ensure best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVD) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. MethodsContrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD) and liver transplant (LTx)-free survival within one-year of follow up. ResultsOverall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine and more often received a TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (HR: 1.756 95%CI: 1.011-3.048 p=0.046) and HD (HR: 1.841 95%CI: 1.255-2.701 p=0.002). However, LTx-free survival was comparable between patients with and without IPVD (HR: 1.081 95%CI: 0.630-1.855, p=0.780). Patients with HPS displayed a trend towards more CD (HR: 1.708 95%CI: 0.935-3.122, p=0.082) and HD (HR: 1.458 95%CI: 0.934-2.275, p=0.097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared to patients without HPS, respectively (HR: 1.052 95%CI: 0.577-1.921, p=0.870). ConclusionScreening for IPVD before TIPS implantation could help to further identify patients at higher risk of cardiac and hepatic decompensation.

The Role of the Anaesthesiologist in Liver Transplantation - Preoperative Evaluation

Preoperative evaluation prior to listing for orthotopic liver transplantation (LT) requires a careful multidisciplinary approach with specialized teams including surgeons, hepatologists and anesthesiologists in order to improve short- and long-term clinical outcomes. Due to inadequate supply of donor organs and changing demographics, patients listed for LT have become older, sicker and share more comorbidities. As cardiovascular events are the leading cause for early mortality precise evaluation of risk factors is mandatory. This review focuses on the detection and management of coronary artery disease, cirrhotic cardiomyopathy, portopulmonary hypertension and hepatopulmonary syndrome in patients awaiting LT. Further insights are being given into scoring systems, patients with Acute-on-chronic-liver-failure (ACLF), frailty, NASH cirrhosis and into psychologic evaluation of patients with substance abuse.

Oxidative stress as one of the pathogenetic mechanisms of hepatopulmonary syndrome in patients with liver cirrhosis

Background. Hepatopulmonary syndrome is one of the most dangerous syntropies in case of liver cirrhosis. Consequently, it is important to determine the role of oxidative stress, acid-base balance and ventilation-perfusion disorders as factors of hepatopulmonary syndrome development in cirrhotic patients. Materials and methods. We included 44 cirrhotic patients with hepatopulmonary syndrome verified according to the patented Method for diagnosing degrees of hepatopulmonary syndrome severity in patients with liver cirrhosis. In addition to the traditional examinations, we determined the gas composition parameters in venous blood, acid-base balance parameters, catalase activity and malondialdehyde level in all the patients. The received material was processed on a personal computer using Excel 2010, Statistica 6.0, RStudio v. 1.1.442 and R Commander v. 2.4-4. Results. Analysis of blood gas parameters revealed the reliability of the difference for PCO2 (р = 0.03) depending on the class of liver cirrhosis severity. Also, with the liver cirrhosis severity increase, the malondialdehyde level increased, and catalase decreased. Moreover, significant inverse relationships between malondialdehyde content and PCO2 (p = 0.039), HCO3 (p = 0.039), TCO2 (p = 0.036), Beb (p = 0.049), BEecf (p = 0.043) were found resulting in hypocapnia and partially compensated metabolic acidosis. The found direct correlation between malondialdehyde level and AaDO2 (p = 0.044) indicates the arteriovenous pulmonary shunts, ventilation-perfusion disorders. The absence of catalase content changes can obviously be explained by the fact that its activity can be partially compensatory maintained. Conclusions. In patients with hepatopulmonary syndrome, the peroxidation activity enhances with an increase in the liver cirrhosis severity, resulting in the redox homeostasis imbalance, leading to the ventilation-perfusion disorders and partially compensated metabolic acidosis.

Prevalence and prognostic impact of hepatopulmonary syndrome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization: a prospective cohort study.

To determine the prevalence and prognostic impact of hepatopulmonary syndrome (HPS) in patients with unresectable hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). Fifty-four patients with unresectable HCC undergoing TACE between December 2014 and December 2015 were prospectively screened for HPS and were followed up for a maximum of 2 years or until the end of this prospective study. Nineteen of the 54 (35.2%) patients were considered to have HPS, including one (5.3%) with severe HPS, nine (47.4%) with moderate HPS, and nine (47.4%) with mild HPS. The median overall survival (OS) was 10.1 (95% confidence interval [CI], 3.9-16.3) months for patients with HPS and 15.1 (95% CI, 7.3-22.9) months for patients without HPS, which is not a significant difference ( P = 0.100). The median progression-free survival was also not significantly different between patients with and without HPS (5.2 [95% CI, 0-12.8] vs. 8.4 [95% CI, 3.6-13.1] months; P = 0.537). In the multivariable Cox regression analyses, carbon monoxide diffusing capacity (hazard ratio [HR] = 1.033 [95% CI, 1.003-1.064]; P = 0.028) and Child-Pugh class (HR = 1.815 [95% CI, 1.011-3.260]; P = 0.046) were identified to be the independent prognostic factors of OS. Mild or moderate HPS is common in patients with unresectable HCC undergoing TACE, but it does not seem to have a significant prognostic impact.

Impact of hepatopulmonary syndrome in liver transplantation candidates and the role of angiogenesis.

Hepatopulmonary syndrome affects 10-30% of patients with cirrhosis and portal hypertension. We evaluated the serum angiogenic profile of hepatopulmonary syndrome and assessed the clinical impact of hepatopulmonary syndrome in patients evaluated for liver transplantation. The Pulmonary Vascular Complications of Liver Disease 2 study was a multicentre, prospective cohort study of adults undergoing their first liver transplantation evaluation. Hepatopulmonary syndrome was defined as an alveolar-arterial oxygen gradient ≥15 mmHg (≥20 mmHg if age >64 years), positive contrast-enhanced transthoracic echocardiography and absence of lung disease. We included 85 patients with hepatopulmonary syndrome and 146 patients without hepatopulmonary syndrome. Patients with hepatopulmonary syndrome had more complications of portal hypertension and slightly higher Model for End-Stage Liver Disease-Na score compared to those without hepatopulmonary syndrome (median (interquartile range) 15 (12-19) versus 14 (10-17), p=0.006). Hepatopulmonary syndrome patients had significantly lower 6-min walk distance and worse functional class. Hepatopulmonary syndrome patients had higher circulating angiopoietin 2, Tie2, tenascin C, tyrosine protein kinase Kit (c-Kit), vascular cell adhesion molecule 1 and von Willebrand factor levels, and lower E-selectin levels. Patients with hepatopulmonary syndrome had an increased risk of death (hazard ratio 1.80, 95% CI 1.03-3.16, p=0.04), which persisted despite adjustment for covariates (hazard ratio 1.79, 95% CI 1.02-3.15, p=0.04). This association did not vary based on levels of oxygenation, reflecting the severity of hepatopulmonary syndrome. Hepatopulmonary syndrome was associated with a profile of abnormal systemic angiogenesis, worse exercise and functional capacity, and an overall increased risk of death.

Heart damage in patients with cirrhosis of the liver

The review outlines the current understanding of the clinical syndrome of heart disease in patients with liver cirrhosis and the development of cirrhotic cardiomyopathy. Patients with cirrhosis of the liver often notice chest pain, palpitations, complaints of arterial hypotension and rapid fatigue. Echocardiography shows that the left ventricular ejection fraction in cirrhosis is preserved at rest and decreases under stress. In some patients with viral liver cirrhosis, there is a decrease in global myocardial deformation (the presence of latent systolic dysfunction). More pronounced impairment of left ventricular diastolic function is recorded in patients with ascites and patients with ChildPugh class B and C. In patients with ascites, unfavorable left ventricular remodeling, left heart cavities enlargement, dilatation of the pulmonary artery and its branches are more common. There is an increase in pulmonary artery pressure, the development of portopulmonary hypertension and hepatopulmonary syndrome in patients with liver cirrhosis. Тhe development of these syndromes leads to a sharp decrease in the quality of life of patients with relatively preserved liver function and a worsening of the prognosis for orthotopic liver transplantation. Аpproximately half of patients with liver cirrhosis have electrophysiological disorders: prolongation of the QT interval, tachycardia, supraventricular and ventricular extrasystoles. To date, there are no clinical guidelines for the management of cirrhotic cardiomyopathy. If a patient with liver cirrhosis develops clinically significant heart failure, then general principles of management of such patients are necessary. It is necessary to limit the use of angiotensin-converting enzyme inhibitors and cardiac glycosides. The combined use of nonselective beta-blockers and nitrates reduce cardiac output and QT interval. The use of potassium canrenoate, lisinopril helps reverse the development of structural and functional changes in left ventricle. The positive effect of antiviral therapy on cardiac hemodynamics in patients with viral cirrhosis was noted. Liver transplantation is known to be an effective treatment for cirrhotic cardiomyopathy, but this treatment may worsen latent heart failure. Thus, in patients with liver cirrhosis, heart damage occurs with the development of cirrhotic cardiomyopathy, while the mechanisms of the development of myocardial dysfunction are not fully understood. Further studies of the development of the syndrome are required for timely diagnosis and clinical intervention to improve the survival of patients.

Clinical outcomes and risk factors of hepatopulmonary syndrome in children

Hepatopulmonary syndrome (HPS) is defined as three distinct features: liver disease, hypoxemia, and intrapulmonary vasodilation. The purpose of this study was to investigate the clinical outcomes of pediatric HPS and to identify the risk factors for HPS in children with biliary atresia (BA). We performed a retrospective cohort study of all children who were diagnosed with HPS between 2000 and 2018 at Seoul National University Hospital. The clinical features and outcomes of the 10 patients diagnosed with HPS were reviewed. To clarify the risk factors of HPS in patients with BA, we reviewed 120 patients diagnosed with BA. Underlying liver disease was BA in 8 patients, portal vein agenesis in 1 patient, and portal vein thrombosis in 1 patient. A total of 7 patients underwent liver transplantation (LT). Currently, all seven patients, including 3 patients with severe HPS, survived after LT. The prevalence of HPS in children with BA was 7%. Polysplenia/interrupted inferior vena was the only risk factor for HPS in BA patients in multivariate analysis. The Pediatric End-Stage Liver Disease score was not associated with the development of HPS. Children with severe HPS undergoing LT had excellent outcomes. Screening for HPS in children with BA is required regardless of the severity of liver diseases.

Endothelin-1 level as a predictor of hepatopulmonary syndrome in liver cirrhosis.

Aim To determine the role of endothelin (ET)-1 in predicting hepatopulmonary syndrome (HPS) in patients with liver cirrhosis. Methods A cross sectional study involving 80 liver cirrhosis patients aged 18 years or older was conducted in Adam Malik General Hospital Medan, Indonesia between July 2017 and June 2018. HPS diagnosis was confirmed from the presence of liver cirrhosis, abnormal oxygenation, and intrapulmonary vascular dilatations (IPVD). ET-1 level was measured from serum sample using ELISA method. Patients with coexisting primary pulmonary pathology and intrinsic heart disease were active smokers, and those who declined to participate were excluded. Statistical analysis was conducted at 95% confidence interval. p<0.05 was considered significant. Results Majority the patients were male (56.3%) and had higher educational background (62.5%). Mean age of the patients was 51.3 (SD=12.6) years. The prevalence of HPS was 21.2%. The patients with HPS had higher ET-1 level compared to those without HPS (p<0.001). The patients with hepatic encephalopathy had 2.917 times higher risk for suffering from HPS, while the patients with Child Pugh score A had lower risk (0.738 times) for having HPS compared to subjects with Child Pugh score B and C. ET-1 level >187.5 mg/L had sensitivity and specificity for predicting HPS in subjects with liver cirrhosis of 82.35% and 81.25%, respectively. Conclusion ET-1 could be used as a promising marker for HPS in patients with liver cirrhosis. ET-1 level of >187.5 mg/l had a good accuracy in predicting HPS in liver cirrhosis patient.

ESOPHAGEAL VARICEAL-PULMONARY VENOUS FISTULA: A RARE CAUSE OF RIGHT TO LEFT SHUNT

SESSION TITLE: Wednesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Esophageal varices are dilated submucosal venous plexus in the lower esophagus due to increased pressure in the portal venous system. We present a patient with esophageal varices which fistularized with a left pulmonary vein, thus creating a right to left shunt. The complications of right to left shunt include predominantly hypoxia, cyanosis and sometimes paradoxical emboli in case of intracardiac shunts. CASE PRESENTATION: 64-year-old gentleman who had a liver transplant in 2013 for Hepatitis C virus and hepatocellular cancer (HCC) which was complicated by HCC recurrence with metastasis. On his routine surveillance imaging he was noted to have an incidental finding of a fistula between his esophageal varices and the left pulmonary vein. This created a right to left shunt. Patient denied any significant respiratory symptoms. He denied orthopnea, platypnea, hemoptysis or cough. The patient was offered referral to Interventional Radiology for possible treatment options; however, he declined interventions and wanted to pursue conservative approach. He was continued on maintenance therapy with regorafenib. DISCUSSION: Right to Left shunts occur due to anatomic or physiologic causes. Anatomic shunts occur when the alveoli are completely bypassed as in the case of intracardiac shunts, intrapulmonary arteriovenous malformations. Physiologic shunts occur due to wasted perfusion of non-ventilated alveoli creating a ventilation-perfusion mismatch. Pulmonary manifestations of liver disease include hepatopulmonary syndrome, porto-pulmonary hypertension and hepatic hydrothorax. Hepatopulmonary syndrome is the most common of these and is a special variant of a right to left shunt. It is associated with intrapulmonary vascular dilatations and arteriovenous connections which are more common in lung bases. These are postulated to be secondary to vasoactive mediators like nitric oxide and inability of the liver to clear pulmonary vasodilators resulting in dyspnea and hypoxia. Classically hepatopulmonary syndrome is associated with platypnea and orthodeoxia. This refers to increased dyspnea and drop in O2 tension respectively from supine to upright positions. Our patient did not have any clinical manifestations as a result of this detected fistula, likely due to the volume of blood shunted being minimal and inadequate to cause symptoms. Hence, he did not need any intervention. Hypothetically though, a variceo-pulmonary venous fistula could become significant in a patient with hepatopulmonary manifestations and may necessitate an intervention based upon symptoms. CONCLUSIONS: This case report brings to light a very rare imaging finding that was incidentally detected which to the best of our knowledge has not been reported before. In the right clinical setting the presence of such a fistula could have clinical relevance and require treatment as well. Reference #1: 1. Krowka MJ, Fallon MB, Kawut SM, et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation 2016; 100:1440. Reference #2: 2. Hopkins WE, Waggoner AD, Barzilai B. Frequency and significance of intrapulmonary right-to-left shunting in end-stage hepatic disease. Am J Cardiol 1992; 70:516. Reference #3: 3. Schenk P, Schöniger-Hekele M, Fuhrmann V, et al. Prognostic significance of the hepatopulmonary syndrome in patients with cirrhosis. Gastroenterology 2003; 125:1042 DISCLOSURES: No relevant relationships by Siddique Chaudhary, source=Web Response No relevant relationships by Neeraja Swaminathan, source=Web Response

9. Prevalence of hepatopulmonary syndrome in patients undergoing pre-liver transplant evaluation in a tertiary hospital in Chennai

Background and Aims: Cirrhosis and portal hypertension are accompanied by vascular alterations in multiple organs. HPS is defined as a widened age-corrected alveolar- arterial oxygen gradient (Aapo2) on room air in the presence or absence of hypoxemia (normal Aapo2 = 15 mm Hg, or 20 mm Hg in patients > 64 years) as a result of intrapulmonary vasodilation. Methods: This was a cross sectional studyconducted at a tertiary care center at Government Stanley Medical College, Chennai, in 63 patients with cirrhosis listed for liver transplantation. Results: Fifteen out of 63 (23.8%) patients were females and 48 out of 63 (76.2%) were males. The range of ages was 12 to 73 years with a mean of 44.42 years with a SD of 11.959 years. The average duration of DCLD was 22.83 months with a SD of 16.2 months. The average MELD score was 16.4 with a SD of 4.937. 1 out of 63 (1.6%) patient was CP class A. 33 out of 63 (52.38%) were CP class B and 29 of 63 (46%) were in CP class C. 12 out of 63 (19.04%) had contrast ECHO showing presence of extra-cardiac shunt suggestive of HPS. Conclusions: The purpose of doing this study was to assess the prevalence of HPS in the cases of DCLD who were undergoing pre liver transplantation evaluation in our centre. We found out that there was a 19.04% prevalence of HPS in our cohort. This is broadly similar to the prevalence of HPS described in other studies. However, there was no significant correlation between the severity of liver disease and the presence of HPS. The authors have none to declare.

38. Prevalence and determinants of hepatopulmonary syndrome in patients with decompensated chronic liver disease

38. Prevalence and determinants of hepatopulmonary syndrome in patients with decompensated chronic liver disease

Hepatopulmonary syndrome

Hepatopulmonary syndrome

Impact of Bacterial Translocation on Hepatopulmonary Syndrome: A Prospective Observational Study.

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. 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>15mmHg). 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. 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±2032ng/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±0.34pg/mL, p<0.001), demonstrating a significant difference between each grade (p<0.05). 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.

Schistosomiasis and hepatopulmonary syndrome: the role of concomitant liver cirrhosis.

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.

MIR196A2 rs11614913 C>T polymorphism correlates with an increased risk of hepatopulmonary syndrome in liver cirrhosis: a case-control study in China.

This case-control study is designed to explore the relationship between microRNA-196a2 (MIR196A2) rs11614913 C>T polymorphism and the risk of hepatopulmonary syndrome (HPS) in liver cirrhosis. From January 2013 to January 2015, 163 liver cirrhosis patients with HPS (case group), 264 liver cirrhosis patients without HPS (control group), and 195 healthy people (normal group) were selected. A DNA extraction kit was used to extract plasma DNA from peripheral blood. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the allele and genotype frequencies of MIR196A2 C>T polymorphism. Real-time quantitative polymerase chain reaction was adopted to detect the relative expression of MIR196A. The frequencies of C allele in the case group were higher than those in the control and normal groups (all P <0.05), whereas no significant difference was found between the control and normal groups, which indicated that MIR196A2 C>T polymorphism was closely associated with an increased risk of HPS in patients with liver cirrhosis. Compared with the normal group, the relative expression of MIR196A in the case group was significantly increased (P <0.05), but there was no significant difference in the control group (P >0.05). In the case group, compared with patients carrying the TT genotype, the relative expression of MIR196A of patients carrying the C allele (CT + CC) evidently increased (P <0.05). The MIR196A2 rs11614913 C>T polymorphism may contribute to an increased risk of HPS in liver cirrhosis patients.

Prevalence, Severity, and Prognostic Effect of Hepatopulmonary Syndrome in Liver Transplant Candidates.

Hepatopulmonary syndrome (HPS) is commonly encountered in the setting of end-stage liver disease (ESLD). Past studies have reported conflicting results in terms of demonstrating an association between HPS and mortality. The aim of this study was to determine the prevalence of HPS in patients with ESLD referred for assessment of transplantation suitability. In addition, we investigated survival rates in the setting of HPS, with and without liver transplantation. The medical records of 524 consecutive patients with ESLD evaluated for potential liver transplantation were retrospectively reviewed. HPS was defined by a reduced partial pressure of oxygen or an elevated alveolar-arterial oxygen gradient and the presence of intrapulmonary vascular dilatation on contrast-enhanced echocardiography. In total, 57 subjects (12%) fulfilled the diagnostic criteria of HPS; 88% of these had mild to moderate HPS. For patients with HPS, the overall survival rates at 1 and 3 years were 95% and 92%, respectively. Liver transplants were received by 245 patients (53%), 26 of whom had HPS. For transplant recipients with HPS, the overall survival rates at 1 and 3 years were 96% and 91%, respectively, compared to 85% and 80% in subjects without HPS. Post-transplantation survival in patients with and without HPS did not differ significantly (HR=0.489, 95% CI: 0.153-1.564; p=0.228). This study demonstrated a high prevalence of IPVD and HPS among patients who were potential candidates for liver transplantation. HPS was mild to moderate in the majority of those affected and had no significant effect on overall survival.

Frequency of Hepatopulmonary Syndrome (HPS) Among Patients With Liver Cirrhosis: A Letter to Editor.

Dear Editor, Hepatopulmonary syndrome (HPS) is a complication of liver disease. It is most frequently related to portal hypertension (with or without cirrhosis), although chronic liver disease of almost any etiology could be related to HPS (1, 2). Moreover, some acute liver diseases are related to HPS, such as ischemic hepatitis (3). HPS can be diagnosed when the following disorders have been approved (1, 4, 5); liver disorder, impaired oxygenation, intrapulmonary vascular anomalies, referred to as intrapulmonary vascular dilatations (IPVDs) and lack of intrinsic cardiopulmonary problem. HPS patients finally develop dyspnea on exertion, at rest, or both, commonly after years of liver disease. Dyspnea may be accompanied by pulmonary findings that are more specific for HPS (1, 6) such as platypnea and orthodeoxia. The frequency of hepatopulmonary syndrome in patients with chronic liver disease is about 4 to 47% regarding the criteria of diagnosis and used methods (7-12). The current study evaluated the prevalence of this complication in patients with cirrhosis. Thirty eight patients with cirrhosis were included in this study. Chest X-ray, air-contrast echocardiography, ABG in supine and standing positions, Tc99 MAA lung perfusion scan, PFT (pulmonary function test), serum bilirubin, PT and albumin were evaluated in patients. Hepatopulmonary syndrome was diagnosed in patients who had intrapulmonary vascular shunting and pulmonary gas exchange abnormalities. Among 38 patients, 28 persons were male (%73.7) and 10 females (%26.3). The mean age was 46.2 ± 13.6 (ranged 18 - 64 years). The most common cause of cirrhosis was hepatitis B. Among 29 patients (%76.3), hepatitis B and among 3 patients (%7.6) hepatitis C was diagnosed. Six patients (%15.8) had cryptogenic cirrhosis. Eleven patients (%28.9) had significant hypoxemia (pa O2 < 70) and 24 patients (%71.1) had not hypoxemia. Using echocardiography, 9 patients (23.7%) had pulmonary shunt. Also using radio isotope scan, 2 patients (%5.3) had pulmonary shunt. No patients with positive results in scan had contrast echocardiography. Therefore, pulmonary shunt frequency was %23.7. Six patients (15.8%) had HPS. Three patients (9.9%) had pulmonary shunt without hypoxemia or elevated p(A-a)O2 that are introduced subclinical HPS or IPVDs. Fourteen patients (%36.8) had child score A, 19 patients (%50) child score B and 5 (%13.2) child score C. The findings of the present study showed the prevalence of HPS and intrapulmonary vascular dilatation syndrome in patients with cirrhosis. Air-contrast echocardiography was more effective in diagnosis of intrapulmonary vascular shunting compared to Tc99 MAA lung perfusion scan. No significant relation was found between sex, age, duration, severity, and primary reason of cirrhosis with hepatopulmonary syndrome, but intrapulmonary vascular shunting was more usual in women patients. Spider angioma, orthodeoxia, low serum albumin, and ascites were determined to be suitable clinical indicators for hepatopulmonary syndrome.

Hepatopulmonary syndrome in children-an update

Hepato-pulmonary syndrome (HPS) is an uncommon complication of liver disease. It can be acute or chronic and occur with or without portal hypertension. The reported frequency of HPS in patients with liver disease ranges between 4% and 32%. It occurs as a result of vasodilatation of the pulmonary vasculature which is most likely to be mediated by nitric oxide (NO). Three components are essential to the definition of HPS: 1. liver disease, 2. intra-pulmonary vascular dilatation (IPVD) and 3. impaired oxygenation. .Disease severity is determined by quantifying the degree of oxygenation impairment. Contrast enhanced echocardiography (CE-TTE) and Tc-99 labeled macro-aggregated albumin lung scan with uptake in brain are the gold standard investigations to diagnose HPS and plan management. Clinical features which are characteristic of HPS include orthodeoxia and platypnea in the presence of liver disease. Although there are anecdotal reports on the use of several drugs in the medical management of HPS, none have been shown to result in either sustained improvement in oxygenation or reduce mortality. Liver transplantation is possible and no longer considered to be contraindicated in HPS. However it is important to carefully select and prioritize patients with HPS for liver transplantation for optimum results.

Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis

Hepatopulmonary syndrome (HPS) occurs in 20-30% of patients with liver cirrhosis and is associated with a >2 fold increased mortality. Endothelial dysfunction seems to play a central role in its pathogenesis. von Willebrand factor antigen (vWF-Ag), an established marker of endothelial dysfunction, is significantly elevated in patients with liver cirrhosis, portal hypertension, and in experimental HPS. Aim of the present study was to evaluate the impact of vWF-Ag as a screening marker for presence of HPS in patients with stable cirrhosis. 145 patients with stable liver cirrhosis were screened for presence of HPS in this prospective cohort type cross sectional diagnostic study. vWF-Ag and SaO2 levels were assessed at time of screening for HPS. Criteria of HPS were fulfilled in 31 (21%) patients. vWF-Ag levels were significantly higher in patients with HPS compared to patients without HPS (p<0.001). Furthermore, vWF-Ag correlated significantly with gas exchange in HPS positive patients (p<0.05). vWF-Ag is an independent predictor of HPS after correction for sex, age, model for endstage-liver disease (MELD), and hepatic venous pressure gradient (HVPG) (OR per 1% increase of vWF-Ag: 1.02, 95% CI: 1.00-1.04, p<0.05). The best cut-off was 328% at a sensitivity of 100% and specificity of 53.5%; positive predictive value: 36.9%; negative predictive value: 100%. HPS is associated with elevated vWF-Ag levels. vWF-Ag may be a useful screening tool for early detection of HPS. Further studies investigating vWF-Ag in HPS will be needed to confirm our findings.

Endothelin-1 Activation of the Endothelin B Receptor Modulates Pulmonary Endothelial CX3CL1 and Contributes to Pulmonary Angiogenesis in Experimental Hepatopulmonary Syndrome

Hepatic production and release of endothelin-1 (ET-1) binding to endothelin B (ETB) receptors, overexpressed in the lung microvasculature, is associated with accumulation of pro-angiogenic monocytes and vascular remodeling in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). We have recently found that lung vascular monocyte adhesion and angiogenesis in HPS involve interaction of endothelial C-X3-C motif ligand 1 (CX3CL1) with monocyte CX3C chemokine receptor 1 (CX3CR1), although whether ET-1/ETB receptor activation influences these events is unknown. Our aim was to define if ET-1/ETB receptor activation modulates CX3CL1/CX3CR1 signaling and lung angiogenesis in experimental HPS. A selective ETB receptor antagonist, BQ788, was given for 2 weeks to 1-week CBDL rats. ET-1 (±BQ788) was given to cultured rat pulmonary microvascular endothelial cells overexpressing ETB receptors. BQ788 treatment significantly decreased lung angiogenesis, monocyte accumulation, and CX3CL1 levels after CBDL. ET-1 treatment significantly induced CX3CL1 production in lung microvascular endothelial cells, which was blocked by inhibitors of Ca(2+) and mitogen-activated protein kinase (MEK)/ERK pathways. ET-1-induced ERK activation was Ca(2+) independent. ET-1 administration also increased endothelial tube formation in vitro, which was inhibited by BQ788 or by blocking Ca(2+) and MEK/ERK activation. CX3CR1 neutralizing antibody partially inhibited ET-1 effects on tube formation. These findings identify a novel mechanistic interaction between the ET-1/ETB receptor axis and CX3CL1/CX3CR1 in mediating pulmonary angiogenesis and vascular monocyte accumulation in experimental HPS.