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      Non-alcoholic fatty liver disease (NAFLD) as a neglected metabolic companion of psychiatric disorders: common pathways and future approaches

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          Abstract

          Background

          Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in over 5% of the parenchyma in the absence of excessive alcohol consumption. It is more prevalent in patients with diverse mental disorders, being part of the comorbidity driving loss of life expectancy and quality of life, yet remains a neglected entity. NAFLD can progress to non-alcoholic steatohepatitis (NASH) and increases the risk for cirrhosis and hepatic carcinoma. Both NAFLD and mental disorders share pathophysiological pathways, and also present a complex, bidirectional relationship with the metabolic syndrome (MetS) and related cardiometabolic diseases.

          Main text

          This review compares the demographic data on NAFLD and NASH among the global population and the psychiatric population, finding differences that suggest a higher incidence of this disease among the latter. It also analyzes the link between NAFLD and psychiatric disorders, looking into common pathophysiological pathways, such as metabolic, genetic, and lifestyle factors. Finally, possible treatments, tailored approaches, and future research directions are suggested.

          Conclusion

          NAFLD is part of a complex system of mental and non-communicable somatic disorders with a common pathogenesis, based on shared lifestyle and environmental risks, mediated by dysregulation of inflammation, oxidative stress pathways, and mitochondrial function. The recognition of the prevalent comorbidity between NAFLD and mental disorders is required to inform clinical practice and develop novel interventions to prevent and treat these complex and interacting disorders.

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          Most cited references64

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          The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population

          Background Fatty liver (FL) is the most frequent liver disease in Western countries. We used data from the Dionysos Nutrition & Liver Study to develop a simple algorithm for the prediction of FL in the general population. Methods 216 subjects with and 280 without suspected liver disease were studied. FL was diagnosed by ultrasonography and alcohol intake was assessed using a 7-day diary. Bootstrapped stepwise logistic regression was used to identify potential predictors of FL among 13 variables of interest [gender, age, ethanol intake, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase (GGT), body mass index (BMI), waist circumference, sum of 4 skinfolds, glucose, insulin, triglycerides, and cholesterol]. Potential predictors were entered into stepwise logistic regression models with the aim of obtaining the most simple and accurate algorithm for the prediction of FL. Results An algorithm based on BMI, waist circumference, triglycerides and GGT had an accuracy of 0.84 (95%CI 0.81–0.87) in detecting FL. We used this algorithm to develop the "fatty liver index" (FLI), which varies between 0 and 100. A FLI < 30 (negative likelihood ratio = 0.2) rules out and a FLI ≥ 60 (positive likelihood ratio = 4.3) rules in fatty liver. Conclusion FLI is simple to obtain and may help physicians select subjects for liver ultrasonography and intensified lifestyle counseling, and researchers to select patients for epidemiologic studies. Validation of FLI in external populations is needed before it can be employed for these purposes.
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            Interactions between the microbiota, immune and nervous systems in health and disease

            The diverse collection of microorganisms that inhabit the gastrointestinal tract, collectively called the gut microbiota, profoundly influences many aspects of host physiology, including nutrient metabolism, resistance to infection and immune system development. Studies investigating the gut-brain axis demonstrate a critical role for the gut microbiota in orchestrating brain development and behavior, and the immune system is emerging as an important regulator of these interactions. Intestinal microbes modulate the maturation and function of tissue-resident immune cells in the CNS. Microbes also influence the activation of peripheral immune cells, which regulate responses to neuroinflammation, brain injury, autoimmunity and neurogenesis. Accordingly, both the gut microbiota and immune system are implicated in the etiopathogenesis or manifestation of neurodevelopmental, psychiatric and neurodegenerative diseases, such as autism spectrum disorder, depression and Alzheimer's disease. In this review, we discuss the role of CNS-resident and peripheral immune pathways in microbiota-gut-brain communication during health and neurological disease.
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              Nonalcoholic Steatohepatitis: A Review

              Nonalcoholic steatohepatitis (NASH) is the inflammatory subtype of nonalcoholic fatty liver disease (NAFLD) and is associated with disease progression, development of cirrhosis, and need for liver transplant. Despite its importance, NASH is underrecognized in clinical practice.
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                Author and article information

                Contributors
                osoto@vhebron.net
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                1 October 2020
                1 October 2020
                2020
                : 18
                : 261
                Affiliations
                [1 ]GRID grid.411083.f, ISNI 0000 0001 0675 8654, Department of Psychiatry, , Vall d’Hebron University Hospital, ; Passeig de la Vall d’Hebron, 119-129, 08035 Barcelona, Catalonia Spain
                [2 ]GRID grid.414257.1, ISNI 0000 0004 0540 0062, Deakin University, IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, , Barwon Health, ; Geelong, Australia
                [3 ]Bipolar and Depressive Disorders Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, 170 Villarroel st, 12-0, 08036 Barcelona, Catalonia Spain
                [4 ]GRID grid.411375.5, ISNI 0000 0004 1768 164X, UGC Salud Mental, , Hospital Universitario Virgen Macarena, ; Seville, Spain
                [5 ]GRID grid.411057.6, ISNI 0000 0000 9274 367X, Department of Psychiatry, , Hospital Clínico Universitario de Valladolid, ; Castilla y León, Spain
                [6 ]GRID grid.17063.33, ISNI 0000 0001 2157 2938, Department of Psychiatry, , University of Toronto, ; Toronto, ON Canada
                [7 ]GRID grid.155956.b, ISNI 0000 0000 8793 5925, Centre for Addiction and Mental Health (CAMH), ; Toronto, ON Canada
                [8 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, , Amsterdam University Medical Center/Vrije Universiteit & GGZinGeest, ; Amsterdam, the Netherlands
                [9 ]GRID grid.1008.9, ISNI 0000 0001 2179 088X, Orygen, The National Centre of Excellence in Youth Mental Health, the Department of Psychiatry, and the Florey Institute of Neuroscience and Mental Health, , The University of Melbourne, ; Parkville, Australia
                Article
                1713
                10.1186/s12916-020-01713-8
                7528270
                32998725
                622b9b6d-cd41-40f9-8315-91ec61859f7b
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 13 May 2020
                : 17 July 2020
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Medicine
                non-alcoholic fatty liver disease,metabolic syndrome,mental disorders,psychiatry,non-alcoholic steatohepatitis,non-communicable disorders,lifestyle,inflammation,oxidative stress,mitochondrial

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