Hepatopulmonary Syndrome Research Articles

Tea polyphenols and Levofloxacin alleviate the lung injury of hepatopulmonary syndrome in common bile duct ligation rats through Endotoxin -TNF signaling

Background & AimsHepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and arterial blood oxygen desaturation in patients with chronic liver disease. Generally, common bile duct ligation (CBDL) rats are a suitable experimental model for studying hepatopulmonary syndrome. Our previous study demonstrated that endotoxin surges markedly, followed by bacterial translocation and the loss of liver immune function in all the stages of CBDL, thereby contributing to the pathogenesis of HPS. However, the mechanisms behind the increase of the endotoxin and how to alleviate it have not yet been elucidated. Pulmonary injury induced by increased bilirubin, endotoxin, and inflammatory mediators occurs in the early and later stages of CBDL. This study assessed the effects of Tea polyphenols (TP) and Levofloxacin on endotoxin reduction and suppression of lung injury in HPS rats in the long and short term, respectively. MethodsMorphological change of pulmonary injury, HPS relative index, endotoxin concentration, and the activation extent of Malondialdehyde (MDA) and Myeloperoxidase (MPO) were evaluated in CBDL rats with or without TP and Levofloxacin for three weeks or six weeks. The inflammation factors of serum, lung tissue, and BALF were then compared at the same condition for the two time periods. This was followed by adoption of the network pharmacology approach, which was mainly composed of active component gathering, target prediction, HPS gene collection, network analysis, and gene enrichment analysis. Finally, the mRNA and protein levels of the inflammatory factors were studied and relative signaling expression was assessed using RT-PCR and Western blot analysis. ResultsThe obtained results indicated that the pulmonary injury manifestation was perceived and endotoxin, MDA, and MPO activation were markedly increased in the early and later stages of CBDL. TP and Levofloxacin treatment alleviated endotoxin infection and inflammation factor expression three weeks and six weeks after CBDL. In addition, Levofloxacin displayed a short time anti-bacterial effect, while TP exerted a long period function. TP and Levofloxacin also reduced TNF-α, TGF-β, IL-1β, PDGF-BB, NO, ICAM-1, and ET-1 expression on the mRNA or protein expression. With regard to the pharmacological mechanism, the network analysis indicated that 12 targets might be the therapeutic targets of TP and Levofloxacin on HPS, namely ET-1, NOs3, VEGFa, CCl2, TNF, Ptgs2, Hmox1, Alb, Ace, Cav1, and Mmp9. The gene enrichment analysis implied that TP and Levofloxacin probably benefited patients with HPS by modulating pathways associated with the AGE-RAGE signaling pathway, the TNF signaling pathway, the HIF-1 signaling pathway, the VEGF signaling pathway, and the IL-17 signaling pathway, Rheumatoid arthritis, Fluid shear stress, and atherosclerosis. Finally, the TNF-α level was mainly diminished on the protein level following CBDL. ConclusionsTP and Levofloxacin could alleviate pulmonary injury for short and long period, respectively, while at the same time preventing endotoxin and the development of HPS in CBDL rats. These effects are possibly associated with the regulation of the Endotoxin -TNF-α pathways.

50 Years Ago in TheJournalofPediatrics: Hepatopulmonary Syndrome: Transplantation Is the Big Difference

50 Years Ago in TheJournalofPediatrics: Hepatopulmonary Syndrome: Transplantation Is the Big Difference

Congenital portosystemic shunt occlusion with an Amplatzer PFO occlusion device: a case report

BackgroundCongenital portosystemic shunts are embryological malformations in which portal venous flow is diverted to the systemic circulation. High morbidity and mortality are seen in patients with concurrent hepatic encephalopathy, hepatopulmonary syndrome, and pulmonary hypertension. Endovascular therapy, in the correct patient population, offers a less invasive method of treatment with rapid relief of symptoms.Case presentationIn this report, we discuss the treatment of a two-year-old male with abnormal chorea-like movements, altered mental status, anisocoria and hyperammonemia diagnosed with an intrahepatic congenital portosystemic shunt between the inferior vena cava and right portal vein. Given the patient’s amenable anatomy and shunt type, embolization was performed with an 18 mm Amplatzer patent foramen ovale occlusion device.ConclusionsPortosystemic shunts are a rare congenital abnormality without universal treatment guidelines. An Amplatzer PFO occlusion device can provide a novel method of shunt closure given appropriate shunt type, size and anatomy.

Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.

Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive biomarkers. The aim of this study was to determine if serum metabolite profiles in patients with NAFLD associate with future liver‐related events. We performed a retrospective single‐center cohort study of 187 participants with biopsy‐proven NAFLD. Metabolomic analysis was performed on serum using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified liver‐related events (variceal bleeding, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatocellular carcinoma, hepatopulmonary or hepatorenal syndrome) by manual chart review between index biopsy (2007‐2013) and April 1, 2018. Generalized linear models and Cox proportional hazards models were used to test the association of metabolites with liver‐related events and time to first liver‐related event, controlling for covariates and fibrosis stage. Over a mean ± SD follow‐up of 6.9 ± 3.2 years, 11 participants experienced 22 liver‐related events. Generalized linear models revealed 53 metabolites significantly associated with liver‐related events (P < 0.05). In Cox proportional hazards modeling, 69 metabolites were significantly associated with time to future liver‐related events (P < 0.05), seven of which met the false discovery rate threshold of 0.10: vitamin E metabolites gamma‐carboxyethyl‐hydroxychroman (gamma‐CEHC) and gamma‐CEHC glucuronide; primary bile acid metabolite taurochenodeoxycholate; serotonin metabolite 5‐hydroxyindoleacetate; and lipid metabolites (i) 2‐hydroxyglutarate, (ii) 3beta,17beta‐diol disulfate 1, and (iii) eicosenoyl sphingomyelin. Conclusion: Metabolites of a primary bile acid, vitamin E, and serotonin were associated with future liver‐related events. Our results suggest metabolite pathways may be useful for predicting which patients with NAFLD are at higher risk for hepatic decompensation.

Патофизиологические аспекты формирования «порочного круга» при повреждении клеток печени и развитии цирроза

This review highlights fundamental knowledge about the processes within a damaged liver cell, mechanisms of fi bro- and angiogenesis, as well as hypoxia and hypoxemia. Th e causes and consequences of endothelial dysfunction, the role of cytokines in vascular remodeling and the formation of hemodynamic disorders are described. Th ese changes lead to disorder of local and systemic hemodynamics in case of liver cirrhosis. Such complications as: hepatopulmonary syndrome and portopulmonary hypertension are also described.

Cardiovascular disorders in patients with congenital portosystemic shunts: 23 years of experience in a tertiary referral centre

Congenital portosystemic shunts are rare vascular malformations that may have an impact on the heart-lung system. Associated congenital and/or acquired heart diseases are poorly reported. To analyse cardiovascular disorders within a large congenital portosystemic shunt population, and develop a diagnostic strategy. Among the 168 consecutive fetuses and children referred for congenital portosystemic shunt (1996-2019), patients presenting with at least one cardiovascular disorder, including congenital heart disease, heart failure, portopulmonary hypertension and/or hepatopulmonary syndrome, were reviewed retrospectively. Cardiovascular disorders were detected using echocardiography and one or more of the following: right-sided heart catheterization; contrast-enhanced transthoracic echocardiography; or lung perfusion radionuclide scan. Overall, 46/168 patients with a congenital portosystemic shunt (27.4%) had one or more clinically significant cardiovascular disorders. Congenital heart disease was present in 28 patients, including six with left heterotaxy. Heart failure was present in six fetuses and 21 neonates (eight without congenital heart disease, and 13 with congenital heart disease). In neonates without congenital heart disease, heart function recovered by the age of 3years. Portopulmonary hypertension was identified in 11 patients (mean age at diagnosis: 9years); it was fatal in one patient, and remained stable in five of six patients after congenital portosystemic shunt closure. In six patients, hepatopulmonary syndrome presented as hypoxia (mean age at diagnosis: 5.3years), which reversed after congenital portosystemic shunt closure. Evaluation and monitoring of the cardiopulmonary status of patients with a congenital portosystemic shunt is mandatory to detect and prevent cardiovascular complications. Furthermore, congenital portosystemic shunts must be sought in patients with unexplained cardiovascular disorders, especially when malformations are present.

Pentoxyfylline for hepatopulmonary syndrome after liver transplantation: case report

Pentoxyfylline for hepatopulmonary syndrome after liver transplantation: case report

A novel application of pulmonary transit time to differentiate between benign and malignant pulmonary nodules using myocardial contrast echocardiography.

Malignant pulmonary nodules (PNs) are often accompanied by vascular dilatation and structural abnormalities. Pulmonary transit time (PTT) measurement by contrast echocardiograghy has used to assess the cardiopulmonary function and pulmonary vascular status, such as hepatopulmonary syndrome and pulmonary arteriovenous fistula, but has not yet been attempted inthe diagnosis and differential diagnosis of PNs. The aim of this work was to evaluate the feasibility and performance of myocardial contrast echocardiography (MCE) for differentiating malignant PNs from benign ones. The study population consisted of 201 participant: 66 healthy participants, 65 patients with benign PNs and 70 patients with malignant PNs. Their clinical and conventional echocardiographic characteristics were collected. MCE with measurements of PTT were performed. There was no difference in age, sex, heart rate, blood pressure, smoking rate, background lung disease, pulmonary function, ECG, myocardial enzymes, cardiac size and function among the healthy participant, patients with benign and malignant PNs (P > 0.05). PTT did not differ significantly in patients with PNs of different sizes, nor did they differ in patients with PNs of different enhancement patterns (P > 0.05). However, the PTT were far shorter (about one half) in patients with malignant PNs than in patients with benign ones (1.88 ± 0.37 vs. 3.73 ± 0.35, P < 0.001). There was no significantly different between patients with benign PNs and healthy participant (3.73 ± 0.35 vs.3.89 ± 0.36, P > 0.05). The area under the receiver operating characteristics curve (AUC) of PTT was 0.99(0.978-1.009) in discriminating between benign and malignant PNs. The optimal cutoff value was 2.78s, with a sensitivity of 98.52%, a specificity of 97.34%, and a accuracy of 97.69%. MCE had a powerful performance in differentiating between benign and malignant PNs, and a pulmonary circulation time of < 2.78s indicated malignant PNs.

Acute Neurological Symptoms After a Liver Transplant

Acute Neurological Symptoms After a Liver Transplant

Analogies and differences between cirrhotic cardiomyopathy and hepatopulmonary syndrome.

Cirrhotic cardiomyopathy and hepatopulmonary syndrome are two quite frequent clinical entities that may complicate the course of liver cirrhosis. The common pathophysiological origin and the same clinical presentation make them difficult to compare. Cirrhotic cardiomyopathy and hepatopulmonary syndrome may start with dyspnea and breathlessness but the former is characterized by a chronic cardiac dysfunction and the latter by a defect of oxygenation due to pulmonary shunts formation. The focus is to differentiate them as soon as possible since the treatment is different until the patient undergoes liver transplant that is the real unique cure for them.

Largest Cohort Study of Gaucher Disease Type 3 from a Single Center in Egypt Spanning Two Decades

Background and objectives:Gaucher disease (GD) is renowned for genotype/phenotype studies and therapeutic innovation. However, the vast majority of the literature is focused on Type 1 GD related to the founder mutation, p.Asn409Ser in GBA gene although p.Leu483Pro GBA mutation associated GD may be far more prevalent across the world. In Egypt GD represents as high as 14.7% of all reported lysosomal disorders with the neuronopathic forms. Therefore, a large single center cohort study of a highly consanguineous GD population has the potential to inform genotype/phenotype, natural history studies and illuminate unmet needs. Methods:At University of Cairo's Pediatric Hematology Clinic since 1998, we have managed a total of 156 patients with GD with longitudinal data captured under an approved IRB protocol. In the present study, we focused analysis on 85 patients in whom we had long-term outcome after 20 years of enzyme replacement therapy (ERT). GBA gene analysis was performed by whole exome sequencing of DNA isolated from dry blood spots. Data on the clinical phenotype indicators at baseline and during ERT were collected including liver and spleen volumes, growth parameters, bone status, neurological assessment and eye movement. SPSS (Statistical Package for the Social Sciences) version 24 was used to compile data, assess significance and survival by Kaplan Meier analysis. Overall survival (OS) is defined as date of diagnosis till date of death, patients alive or lost during follow up was considered censored till the last date of follow up. Results:The median age at diagnosis was 1 year (IQR: 0.08-15 years) with majority (64.7%) diagnosed in first 2 years of life (range 0.5-2 yrs). The patient population was highly consanguineous and 51% of the patients reported positive family history of GD. The most prevalent genotype (75% of patients) was p.Leu483Pro homozygous. Homozygosity for p.Asp448His was present in 11% of patients. Other GBA mutations included: p.Leu483Pro homozygous in 3 patients, one heteroallelic with p.Leu483Pro; pArg87Trp homozygous in 2 patients; p.Arg398Gln homozygous in one patient). Hematological features of patients at diagnosis revealed anemia in 76% and thrombocytopenia in 22%. Massive splenomegaly (˃15 Multiples of Normal by ultrasonography) was present in 49%, 4 patients were splenectomised, hepatomegaly (˃2.5 MN) in 11%, liver cirrhosis with hepatopulmonary syndrome in one patient. Skeletal findings included multiple fractures in 3 patients and kyphosis in 3 patients. The most common neurological findings were oculomotor apraxia, squint and bulbar symptoms (48%, 30.6% and 29.4% respectively). Bone marrow examination showed Gaucher cell infiltration in 76% of the patients. Patients received Imiglucerase (Cerezyme) dose individualized by baseline disease severity. Debilitating and potentially life-threatening visceral and hematologic disease was reversed with ERT (table 1). One splenectomized patient with massive hepatomegaly and hepatopulmonary syndrome showed complete reversal on high dose ERT. Preliminary observer reported outcomes (by clinician and parent) with respect to neurological findings including oculomotor apraxia appeared to show mild improvement. Follow-up of 10 patients in whom ERT was initiated early had striking overall outcomes progressing through school and university. At 20 years, the overall survival was 71%; 20 patients died from disease complications mostly pulmonary and progressive neurological disease. Comparison of the OS in relation to gender, age at diagnosis, severity of hematological and visceral parameters showed that none of the studied variables affects OS (p˃0.05) (fig. 1). Conclusion:This study represents the largest and most extensive single-center cohort of GD3 patients with predominant p.Leu483Pro homozygous GBA genotype, without presence of a complex allele. Patients had uniformly very early-onset disease before age 2 years with devastating hematological and visceral disease which was effectively reversed by ERT. During 20 year-follow up of the cohort, there was striking reversal of hematovisceral disease and about a third of the patients succumbed to complications of GD3. OS was not correlated with severity of baseline disease underscoring the potential role of modifier genes. Disclosures No relevant conflicts of interest to declare.

Correlation between hepatopulmonary syndrome and oxygen saturation pulse oximetry in cirrhotic patients.

Hepatopulmonary Syndrome (HPS) is a complication of cirrhosis that worsens the disease's prognosis, pre and post liver transplant. The objective of this study is to analyze the prevalence of HPS in cirrhotic patients at our service and to correlate it with oxygen saturation (SatO2) using a pulse oximeter to evaluate if this is useful as a screening test for HPS. A prospective study was conducted in patients with hepatic cirrhosis conventionally selected from 2014 to 2016. All the patients underwent an echocardiogram with microbubbles and oxygen saturation measurement by pulse oximetry. Those with intrapulmonary shunt were submitted to arterial blood gas analysis. The relationship between oxygen saturation and HPS was assessed by the multivariate model of binary logistic regression. We analyzed 77 patients, and 23.3% (18 patients) had all criteria for HPS. The relationship between HPS and SatO2 did not show statistical significance, even after the variables were adjusted for sex, age, and smoking. Oxygen saturation alone was not able to detect HPS in the sample of cirrhotic patients. More accurate methods for screening and diagnosis of the syndrome should be used.

Особливості перебігу алкогольної хвороби печінки на стадії цирозу у поєднанні з неалкогольною жировою хворобою печінки

SummaryThe purpose was to study the features of clinical and laboratory manifestations ofalcoholic liver disease at the cirrhosis stage associated with non-alcoholic fatty liverdisease.Material and methods. Clinical, laboratory and instrumental examinations wereperformed for 204 patients with hepatic cirrhosis. 78 persons had alcoholic liver disease(Group I) and 126 persons had a combination of alcoholic liver disease with nonalcoholic fatty liver disease (Group II). Group I included 24 women and 54 men(53.2±7.6) years old; 22 women and 104 men (47.8±6.4) years old belonged to GroupII. Patients of Groups I and II were allocated to subgroups according to the classes ofhepatic cirrhosis compensation according to the Child-Pugh criteria: IA (17 patients),IB (38 patients), IC (23 patients); IIA (44 patients), ІІВ (48 patients), ІІС (34 patients).Results and discussion. It was found that the signs of astheno-vegetative, pain,dyspeptic, hepatorenal, hepatopulmonary syndromes, jaundice, medically uncontrolledascites, and manifestations of hepatic encephalopathy were shown more often amongpatients in combination with non-alcoholic fatty liver disease. Somatometric indicessignificantly differed among all patients depending on the degree of compensation. Thethickness of the skin and fat fold are reliable indicators that reflect the state of the fatdepot of the body; the circumference of shoulder muscles is a reliable indicator of thereduction of the somatic protein pool, accompanied by a decrease in the syntheticfunction of the liver and a decrease in the somatic protein pool, especially amongpatients associated with non-alcoholic fatty liver disease.Conclusions. During examining patients with liver cirrhosis, the study of the trophicstatus, synthetic function, and functional state of the liver are recommended for timelycorrection of the revealed disorders.

High-flow nasal cannula oxygen therapy: Alternative respiratory therapy for severe post-transplant hypoxemia in children with hepatopulmonary syndrome.

Severe post-transplant hypoxemia, which is defined as <50mmHg of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F) ratio, is a major post-operative complication with high mortality rates in patients with hepatopulmonary syndrome (HPS). Non-invasive positive pressure ventilation therapy and mechanical ventilation are options for respiratory support of patients with severe post-transplant hypoxemia. However, these therapies are associated with several problems, such as compliance, ventilator-associated pneumonia, and lung injury. We here firstly described two children with HPS who developed severe post-transplant hypoxemia (lowest post-operative P/F ratio, 49.7 and 34.0mmHg, respectively) that was successfully managed with high-flow nasal cannula (HFNC) oxygen therapy and vasodilation drugs without adverse complications or necessity of reintubation. We consider that HFNC oxygen therapy could become a safe alternative respiratory therapy or be added to the other such as inhaled nitric oxide (iNO), methylene blue (MB), inhaled epoprostenol, embolization of abnormal pulmonary vessels, and combination of iNO and MB for severe post-transplant hypoxemia in children with HPS.

Transjugular intrahepatic portosystemic shunt in cirrhosis: An exhaustive critical update

More than five decades after it was originally conceptualized as rescue therapy for patients with intractable variceal bleeding, the transjugular intrahepatic portosystemic shunt (TIPS) procedure continues to remain a focus of intense clinical and biomedical research. By the impressive reduction in portal pressure achieved by this intervention, coupled with its minimally invasive nature, TIPS has gained increasing acceptance in the treatment of complications of portal hypertension. The early years of TIPS were plagued by poor long-term patency of the stents and increased incidence of hepatic encephalopathy. Moreover, the diversion of portal flow after placement of TIPS often resulted in derangement of hepatic functions, which was occasionally severe. While the incidence of shunt dysfunction has markedly reduced with the advent of covered stents, hepatic encephalopathy and instances of early liver failure continue to remain a significant issue after TIPS. It has emerged over the years that careful selection of patients and diligent post-procedural care is of paramount importance to optimize the outcome after TIPS. The past twenty years have seen multiple studies redefining the role of TIPS in the management of variceal bleeding and refractory ascites while exploring its application in other complications of cirrhosis like hepatic hydrothorax, portal hypertensive gastropathy, ectopic varices, hepatorenal and hepatopulmonary syndromes, non-tumoral portal vein thrombosis and chylous ascites. It has also been utilized to good effect before extrahepatic abdominal surgery to reduce perioperative morbidity and mortality. The current article aims to review the updated literature on the status of TIPS in the management of patients with liver cirrhosis.

Modeling Outcomes in Children With Biliary Atresia With Native Liver After 2 Years of Age.

Approximately 50% of infants with biliary atresia (BA) undergoing Kasai portoenterostomy show survival with native liver (SNL) at age 2 years. Predictors of disease progression after age 2 years are unknown, despite estimates of 20%‐30% undergoing liver transplant (LT) between age 2 and 18 years. We sought to address this knowledge gap by developing prognostic models in participants of the multicenter prospective National Institutes of Health‐supported Childhood Liver Disease Research Network. We extracted 14 clinical and biochemical variables at age 2 years to develop two models for future outcomes: 1) LT or death (LTD) and 2) first sentinel event (SE), either new onset ascites, hepatopulmonary syndrome (HPS), or gastrointestinal (GI) bleed. A total of 240 participants, enrolled between 2004 and 2017, were followed until a median age of 5.1 years (range, 2.0‐13.3 years). Of these participants, 38 underwent LT (n = 37) or death (n = 1); cumulative incidence, 23.7% (95% confidence interval [CI], 16.2%‐32.0%). Twenty‐seven experienced either new‐onset ascites (n = 13), HPS (n = 1), or GI bleed (n = 14). One participant had ascites and GI bleed concurrently; cumulative incidence, 21.5% (95% CI, 14.2%‐29.8%) by age 10 years. The Cox proportional hazard model predicted risk of LTD, using total bilirubin, albumin, platelet count, and history of either ascites or cholangitis (BA LTD model), with a C‐index of 0.88 (range, 0.86‐0.89). A cause‐specific hazard competing risk model predicted SE using platelet count and gamma glutamyltransferase levels (BA SE model) with a C‐index of 0.81 (range, 0.80‐0.84). Internal model validity was assessed using Harrell’s C‐index with cross‐validation. Conclusion: Stratification using these models identified risk of poor outcomes in patients with BA SNL after age 2 years. The models may identify those who would benefit from enhanced clinical surveillance and prioritization in clinical trials.

S2693 Outcome of Hepatitis C Virus-Positive Liver Transplantation for Telomere-Mediated HPS-Noncirrhotic Portal Hypertension After Bone Marrow Transplantation: A Case Report

INTRODUCTION: Short telomere syndromes are disorders caused by germline mutations in genes regulating telomere maintenance. Their phenotypes and severity vary and depend on the extent of telomere shortening. Dyskeratosis congenita (DC) is a prototypic short telomere syndrome, characterized by bone marrow failure, liver disease (noncirrhotic portal hypertension, cryptogenic cirrhosis), pulmonary fibrosis and an increased risk of malignancy. With contemporary hematopoietic stem cell transplantation (HSCT) regimens, non-cirrhotic portal hypertension with hepatopulmonary syndrome (HPS) is the most common morbidity. We describe successful HCV-positive liver transplantation (LT) for telomere-mediated noncirrhotic portal hypertension with HPS after HSCT. CASE DESCRIPTION/METHODS: A 27-year-old female with DC complicated by noncirrhotic portal hypertension and HPS underwent LT at age 25, from a 23-year-old, HCV-positive, female donor. The recipient was diagnosed with bone marrow failure and DC at age 17. At that time, telomere length was below the 1st age-adjusted percentile, but she had no identifiable mutation. She underwent a non-myeloablative HSCT at age 19. Three years later, she presented with progressive dyspnea and was found to have stigmata of portal hypertension and intrapulmonary shunt. A trans-jugular liver biopsy confirmed the absence of significant fibrosis with a hepatic venous pressure gradient of 10 mmHg. Her dyspnea continued to progress with minimal evidence of parenchymal pulmonary fibrosis but worsening HPS. She was on 10 L oxygen prior to LT with room air PO2 55 mmHg, qualifying for UNOS upgrade to MELD 29. Liver explant pathology revealed focal parenchymal nodularity and absence of significant fibrosis. She had a prolonged recovery due to respiratory failure and malnutrition, which she recovered from and completely weaned off oxygen four months post-LT. She was successfully treated for HCV post-LT. She had recurrent low-level CMV viremia and presumed mild graft rejection episode. Sixteen months post-LT, she continues to be on room air with stable lung and liver graft function. DISCUSSION: The natural history of short telomere syndromes is marked by progressive noncirrhotic portal hypertension with HPS, a frequent long-term complication after HSCT. We report a successful LT and reversal of hypoxemia after an HCV-positive LT in a patient with DC. Sequential transplant may be feasible option for post-HSCT patients who develop end-stage liver disease.

S2501 Cardiopulmonary Failure and Stroke in a Patient With PFO Following Liver Transplant: A Case Report

INTRODUCTION: Patent foramen ovale (PFO) is the most common congenital heart anomaly, and currently affects roughly 20–25% of adults worldwide. This defect allows direct blood flow between the right and left atria with interatrial shunting and increased risk of stroke due to paradoxical embolism. These potential complications are particularly concerning in patients undergoing liver transplant especially those with hepatopulmonary syndrome (HPS) and when using the piggyback operative technique. Two studies evaluated short-term outcomes including neurologic events in patients undergoing liver transplant surgery. Both reported no statistically significant difference in outcomes/neurologic events between patients with or without PFO undergoing transplant. The purpose of this case report is to discuss a patient with known PFO without closure who underwent liver transplantation, and suffered from an MRI-proven stroke and significant cardiopulmonary compromise. CASE DESCRIPTION/METHODS: A 60-year-old female with history of NASH cirrhosis, HPS, and atrial fibrillation with known, asymptomatic PFO as evidenced by interatrial shunting on transthoracic echocardiogram underwent liver transplant with uncomplicated surgery. However, her hospital course was complicated by pneumonia. She was difficult to wean from the ventilator, prompting initiation of extracorporeal membranous oxygenation (ECMO) ten days post-transplant. She remained on ECMO for eleven days, and due to her continued desaturation when weaning from ECMO, underwent percutaneous PFO closure. Roughly two-weeks post-PFO closure, she was noted to have right-sided weakness and right-sided facial droop when weaned from sedation. MR brain showed infarction in the anterior left medulla. DISCUSSION: The etiology of this patient's complicated post-operative course is multifactorial including pneumonia, underlying HPS and underlying PFO. This case questions the current standard of care for patients pre-transplant with known PFO. While the existing data suggests there is no indication for prophylactic PFO closure, some authors recommend considerations for closure in the presence of HPS. Some liver transplant centers recommend routine closure of PFO prior to liver transplant. Further studies are needed to define the population at high risk for paradoxical embolization and other complications of shunting that would benefit from PFO closure prior to liver transplant.

S2722 Abernethy Malformation Causing Recurrent Hepatic Encephalopathy

INTRODUCTION: Hepatic encephalopathy (HE) is a spectrum of neuropsychiatric abnormalities in patients with underlying liver dysfunction such as acute liver failure (type A) or cirrhosis (type C). Less commonly, it involves patients with acquired or congenital portosystemic shunt (PSS) in the absence of hepatocellular disease (type B). CASE DESCRIPTION/METHODS: A 70-year-old female with a past medical history of chronic pain, CHF, lymphedema and prior recurrent encephalopathy, presented with altered mental status and seizure-like activity. Vital signs were stable and laboratory studies including CBC, BMP and LFTs were normal except for an ammonia level of 272 umol/L. She denied any prior history of liver disease and was previously informed that the hyperammonemia was secondary to her use of narcotics for chronic pain. CT chest and abdomen was obtained which revealed normal appearing liver, prominent azygos vein and side-to-side porto-azygos shunt (Figures 1 and 2). A liver US indicated normal echotexture with patent vasculature. Liver biopsy showed normal portal triads with mild steatosis and minimal sinusoidal dilatation. She was treated with lactulose until resolution of HE and was eventually discharged. Given the absence of liver disease, the PSS likely represent a congenital malformation that has been perpetuating the HE. DISCUSSION: In the presence of a PSS, underlying liver disease should be excluded to ensure the etiology of the shunt is not a result of portal hypertension. Congenital PSS were first described in 1793 by J. Abernethy and are classified as type 1 which involves an end-to-side porto-caval shunt with absence of the portal vein (PV), and type 2 which consists in a side-to-side shunt with an intact PV. Congenital PSS may also be associated with other abnormalities including biliary atresia, polysplenia, in addition to cardiac, skeletal and renal malformations. HE, which occurs as a complication of the shunt bypassing the hepatic conversion of ammonia to urea, is the most common neurologic complication. In addition, acquired cardiopulmonary complications are also common due to volume overload. Patients with symptomatic congenital PSS should be considered for PSS closure, whether endovascular or surgical. In patients with type 2 shunt, obliteration of the PSS can reverse HE from hyperammonemia and potentially resolve heart failure and hepatopulmonary syndrome but rarely causes regression of pulmonary hypertension. Acute portal hypertension as well as thrombosis have been reported after closure.Figure 1.: Prominent Azygos vein on coronal view.Figure 2.: Side to side portal to azygos vein shunt.

PLATYPNEA-ORTHODEOXIA SYNDROME DUE TO A BIDIRECTIONAL SHUNT

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Platypnea-orthodeoxia syndrome is a rare disorder characterized by dyspnea and arterial desaturation in an upright position with improvement in the supine position (1). Our case highlights a known but rather uncommon and reversible cause of hypoxia which can potentially be misdiagnosed. CASE PRESENTATION: A 62-year-old male with a history of hypertension and type 2 diabetes mellitus presented to the emergency department with gradual, progressive, intermittent, dyspnea for 2 months, which was worse with standing and walking, and better after laying flat. The patient stated that he used to walk a few miles without any discomfort approximately one year ago. But now the dyspnea had limited his ability to walk less than one block. As per records, the patient had a cardiac catheterization 1 month back for an abnormal stress test and it showed angiographically normal coronaries and 60% ejection fraction. No recent sick contacts and no family history of cardiac conditions. Vitals on presentation revealed tachycardia, respiratory rate of 20/min, 99% O2 saturation on lying flat, and 84% on standing up which dropped to 78% after walking 10 steps. The hypoxia while standing up didn't resolve with nasal cannula oxygenation. Labs were within normal limits. Chest X-ray showed normal lung fields and normal heart shadow, CT pulmonary angiogram was normal. 2D Echocardiography with a bubble study showed a left ventricular ejection fraction of 55 % and a patent foramen ovale (PFO). Transesophageal echocardiography (TEE) showed large atrial septal defect with left-to-right shunting and no right-to-left shunting. The patient was scheduled to undergo surgical closure of the defect. DISCUSSION: PFO was found in 25 to 30 percent of individuals in an autopsy study and a community-based transesophageal echocardiography (TEE) study (2). Two required components of a PFO are an interatrial shunt or an intrapulmonary shunt as in the hepatopulmonary syndrome, and a functional component that promotes abnormal shunting when the patient rises from a recumbent to an upright position. Our patient had both these components due to a left to right shunt. CONCLUSIONS: Platypnea-orthodeoxia syndrome can be presented as mere dyspnea on effort. A clinician should check the positional change of symptoms and/or oxygenation when he or she sees a patient with dyspnea on effort of undetermined origin. Preexisting bidirectional shunting precipitated in its right-to-left component by Valsalva maneuver, coughing, or straining might explain the occurrence of a paradoxical embolism in Secundum atrial septal defect patients(3). Definitive treatment in the form of closure is recommended in such cases. Reference #1: 1. Cheng TO. Platypnea-orthodeoxia syndrome: etiology, differential diagnosis, and management. Catheter Cardiovasc Interv. 1999;47(1):64-66. https://doi.org/10.1002/(SICI1522-726X(199905)47:1<64::AID-CCD15>3.0.CO;2-6) Reference #2: 2. Hagen PT, Scholz DG, Edwards WD. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc. 1984;59(1):17-20. https://doi.org/10.1016/s0025-6196(1260336-x) Reference #3: 3. Rigatelli G, Dell'avvocata F, Tarantini G, Giordan M, Cardaioli P, Nguyen T. Clinical, hemodynamic, and intracardiac echocardiographic characteristics of secundum atrial septal defects-related paradoxical embolism in adulthood. J Interv Cardiol. 2014;27(6):542-547. https://doi.org/10.1111/joic.12159 DISCLOSURES: No relevant relationships by Sanya Chandna, source=Web Response No relevant relationships by Monarch Shah, source=Web Response