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      Non-alcoholic Fatty Liver Disease Causing Platypnea-Orthodeoxia Syndrome

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          Abstract

          Non-alcoholic fatty liver disease (NAFLD) with cryptogenic liver cirrhosis is uncommonly linked to platypnea-orthodeoxia syndrome (POS). Traditionally, this syndrome has been described in correlation to intracardiac shunting like patent foramen ovale. 

          We report a case of a 70-year-old female, with a previous history of NAFLD and heart failure presenting with acute hypoxic respiratory failure secondary to fluid overload. Further investigations revealed cryptogenic presentation of POS, which was masked by her heart failure. The patient was not able to maintain her oxygen saturation levels in an upright position, with marked improvement when lying down. Her echocardiogram was significant for positive bubble study without any intracardiac shunt, hence making NAFLD as a cause of this rare presentation of POS a more likely diagnosis.

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          Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study.

          Joseph D. Williams, Margarita C. T. Slof-Op’t Landt, Thomas Harrison … (2010)
          Prevalence of nonalcoholic fatty liver disease (NAFLD) has not been well established. The purpose of this study was to prospectively define the prevalence of both NAFLD and nonalcoholic steatohepatitis (NASH). Outpatients 18 to 70 years old were recruited from Brooke Army Medical Center. All patients completed a baseline questionnaire and ultrasound. If fatty liver was identified, then laboratory data and a liver biopsy were obtained. Four hundred patients were enrolled. Three hundred and twenty-eight patients completed the questionnaire and ultrasound. Mean age (range, 28-70 years) was 54.6 years (7.35); 62.5% Caucasian, 22% Hispanic, and 11.3% African American; 50.9% female; mean body mass index (BMI) (calculated as kg/m(2)) was 29.8 (5.64); and diabetes and hypertension prevalence 16.5% and 49.7%, respectively. Prevalence of NAFLD was 46%. NASH was confirmed in 40 patients (12.2% of total cohort, 29.9% of ultrasound positive patients). Hispanics had the highest prevalence of NAFLD (58.3%), then Caucasians (44.4%) and African Americans (35.1%). NAFLD patients were more likely to be male (58.9%), older (P = .004), hypertensive (P < .00005), and diabetic (P < .00005). They had a higher BMI (P < .0005), ate fast food more often (P = .049), and exercised less (P = 0.02) than their non-NAFLD counterparts. Hispanics had a higher prevalence of NASH compared with Caucasians (19.4% vs 9.8%; P = .03). Alanine aminotransferase, aspartate aminotransferase, BMI, insulin, Quantitative Insulin-Sensitivity Check Index, and cytokeratin-18 correlated with NASH. Among the 54 diabetic patients, NAFLD was found in 74% and NASH in 22.2%. Prevalence of NAFLD and NASH is higher than estimated previously. Hispanics and patients with diabetes are at greatest risk for both NAFLD and NASH. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
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            Non-alcoholic fatty liver disease (NAFLD) – pathogenesis, classification, and effect on drug metabolizing enzymes and transporters

            Fatemeh Akhlaghi, Enoch Cobbina (2017)
            Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disorders. It is defined by the presence of steatosis in more than 5 % of hepatocytes with little or no alcohol consumption. Insulin resistance, the metabolic syndrome or type 2 diabetes and genetic variants of PNPLA3 or TM6SF2 seem to play a role in the pathogenesis of NAFLD. The pathological progression of NAFLD follows tentatively a ‘three-hit’ process namely steatosis, lipotoxicity and inflammation. The presence of steatosis, oxidative stress and inflammatory mediators like TNF-α and IL-6 have been implicated in the alterations of nuclear factors such as CAR, PXR, PPAR-α in NAFLD. These factors may results in altered expression and activity of drug metabolizing enzymes (DMEs) or transporters. Existing evidence suggests that the effect of NAFLD on CYP3A4, CYP2E1 and MRP3 are more consistent across rodent and human studies. CYP3A4 activity is down-regulated in NASH whereas the activity of CYP2E1 and the efflux transporter MRP3 are up-regulated. However, it is not clear how the majority of CYPs, UGTs, SULTs and transporters are influenced by NAFLD either in vivo or in vitro . The alterations associated with NAFLD could be a potential source of drug variability in patients and could have serious implications for the safety and efficacy of xenobiotics. In this review, we summarize the effects of NAFLD on the regulation, expression and activity of major drug metabolizing enzymes and transporters. We also discuss the potential mechanisms underlying these alterations.
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              The multiple dimensions of Platypnea-Orthodeoxia syndrome: A review

              Abhinav Agrawal, Atul V Palkar, Arunabh Talwar (2017)
              Platypnea-Orthodeoxia syndrome (POS) is a rare clinical entity characterized by dyspnea and arterial desaturation while in the upright position. The various pathophysiologic mechanisms leading to POS has puzzled clinicians for years. The hypoxia in POS has been attributed to the mixing of the deoxygenated venous blood with the oxygenated arterial blood via a shunt. The primary mechanisms of POS in these patients can be broadly classified based on intracardiac abnormalities, extracardiac abnormalities and miscellaneous etiologies. A Patent Foramen Ovale (PFO) was the most common reported site of an intracardiac shunt. In addition to PFO, intracardiac shunt leading to POS has been reported from either an Atrial Septal Defect (ASD) or an Atrial Septal Aneurysm (ASA). Most patients with an intracardiac shunt also demonstrated a secondary anatomic or a functional defect. Extracardiac causes of POS included intra-pulmonary arteriovenous malformations and lung parenchymal diseases. A systematic evaluation is necessary to identify the underlying cause and institute an appropriate intervention. We conducted a review of literature and reviewed 239 cases of POS. In this article, we review the etiology and pathophysiology of POS and also summarize the diagnostic algorithms and treatment modalities available for early diagnosis and prompt treatment of patients presenting with symptoms of platypnea and/or orthodeoxia.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cureus
                Journal ID (iso-abbrev): Cureus
                Journal ID (issn): 2168-8184
                Title: Cureus
                Publisher: Cureus (Palo Alto (CA) )
                ISSN (Electronic): 2168-8184
                Publication date (Electronic, pub): 27 November 2020
                Publication date (Electronic, collection): November 2020
                Volume: 12
                Issue: 11
                Electronic Location Identifier: e11727
                Affiliations
                [1 ] Internal Medicine, East Carolina University, Greenville, USA
                [2 ] Internal Medicine, Quaid-E-Azam Medical College, Bahawalpur, PAK
                [3 ] Internal Medicine, United Medical and Dental College, Karachi, PAK
                Author notes
                Article
                DOI: 10.7759/cureus.11727
                PMC ID: 7772170
                SO-VID: f44dce1e-d6f3-4043-a5af-af6addbac8f2
                Copyright © Copyright © 2020, Ali et al.
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date accepted : 26 November 2020
                Categories
                Subject: Cardiology
                Subject: Internal Medicine
                Subject: Gastroenterology

                Keywords: nonalcoholic fatty liver disease (nafld),platypnea,orthodeoxia,heart failure,heart failure with preserved ejection fraction,hypoxic respiratory failure,hepatopulmonary syndrome
                Data availability:
                Keywords: nonalcoholic fatty liver disease (nafld), platypnea, orthodeoxia, heart failure, heart failure with preserved ejection fraction, hypoxic respiratory failure, hepatopulmonary syndrome

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