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Non alcoholic steatohepatitis is the major cause or chronic liver diseases in Western countries. Over the past decade,its prevalence has been constantly increasing in parallel with the obesity and type 2 diabetes. Furthermore, its ability to progress to a more severe stage makes it a major public health problem. There is currently no approved treatment for the management of NAFLD but it seems to be directly linked to the lifestyle; it is thus consistent to think that a change of lifestyle habits may slow the disease progression. In order to highlight this lack of treatment, 28 studies have been analyzed in order to evaluate dietary intervention's effects with or without physical activity. Despite several limitations such as a low number of patients included in the studies, a lack of randomization or a wide range of diagnostic criteria; this analysis allowed us to emphasize the benefits of a weight loss ranging from 5 to 10% of the initial weight in the decrease of both hepatic TG and inflammation. In order to achieve this weight loss, we recommend a hypocaloric diet with carbohydrate restriction and a better fat consumed management. Regular physical activity is also advised for the maintenance of weight loss and improvement of parameters linked to insulin resistance. Finally, we will never stress enough the importance of an early intervention adapted to individuals' needs. La stéatose hépatique non alcoolique représente la première cause de maladie chronique du foie dans les pays occidentaux. Depuis cette dernière décennie, sa prévalence ne cesse d'augmenter en parallèle avec une augmentation de l'obésité et du diabète de type 2. De plus, sa possibilité d'évoluer vers un stade plus sévère de la maladie en fait aujourd'hui un problème de santé publique majeur. Il n'existe actuellement aucun traitement validé dans la gestion de la NAFLD, mais, visiblement liée au mode de vie, il est cohérent de penser qu'une modification des habitudes hygiéno-d diététiques pourrait freiner l'évolution de la maladie. En vue de répondre à cette problématique, 28 études ont été analysées afin d'évaluer les effets de diverses prises en charge diététiques associées ou non à de l'exercice physique. Malgré un certain nombre de limites telles qu'un trop petit nombre de patients inclus dans les études, une absence de randomisation ou encore la grande diversité des critères diagnostiques, cette analyse nous a permis de mettre en avant les bénéfices d'une perte de poids comprise entre 5 et 10% du poids initial dans la diminution des TG hépatiques et de l'inflammation. Pour ce faire, nous recommandons une diète hypocalorique, avec restriction glucidique et un changement qualitatif des graisses consommées. La pratique d'une activité physique régulière est également préconisée pour le maintien de la perte de poids et l'amélioration des paramètres relatifs à l'insulino-résistance. Pour finir soulignons l'importance d'une prise en charge précoce, adaptée à la compliance de chacun.

Non-alcoholic Fatty Liver Disease --- Diet Therapy

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Il semble indéniable que la NASH soit devenue un sujet de préoccupation de santé publique pour lequel la mise en place de solutions spécifiques se trouve être nécessaire au vue des épidémies actuelles d'obésité et de diabète de type II qui s'observent dans les pays développés. La NASH complication hépatique de l'obésité et du syndrome métabolique est une pathologie hépatique qui se caractérise par l'accumulation de graisses sous forme de triglycérides dans les hépatocytes, s'y associe une inflammation, des lésions hépatocellulaires avec ou sans fibrose pouvant évoluer en cirrhose et en hépato carcinome. De plus, la NASH augmente les risques de maladies cardiovasculaires. Au vu de la gravité des diverses complications, un grand besoin de traitements existe puisque actuellement aucun traitement n'a été validé pour cette indication. Genfit a élaboré pour ce faire un candidat médicament, Elafibranor. C'est un double agoniste des PPARs qui possède une activité préférentielle pour PPAR-a et une activité supplémentaire pour PPAR-/ô. Les PPARs ont plusieurs effets métaboliques favorables tels que l'amélioration de la -oxydation des acides gras, du catabolisme des lipides, de la sensibilité à l'insuline et bien d'autres, tout en atténuant l'inflammation hépatique ce qui en font des cibles d'intérêt dans le traitement de la NASH. Actuellement, Elafibranor est rentrée en étude de phase III, au vu des différents résultats prometteurs obtenus lors des phases' précliniques et cliniques. Elafibranor a démontré divers effets bénéfiques prometteurs tels que l'amélioration de l'inflammation, de la stéatose et de la fibrose pour les traitements de la NASH tout en ayant un profil de sécurité satisfaisant. Des questions restent cependant en suspens et nous attendons avec impatience les résultats de la phase III pour déterminer l'avenir d'Elafibranor dans le traitement de la stéatose hépatique non alcoolique. Non-alcoholic fatty liver disease (NAFLD) is a hepatic complication of obesity and metabolic syndrome that affect a wide ride of individuals. As well as, it increases the risk of cardio-vascular diseases. It’ characterized by the accumulation of fat the form of triglycerides in the hepatocytes and is considered to be the most common cause of liver dysfunction in the western countries. It could progress to a more severe disease of hepatic inflammation leading to the development of a non-alcoholic steato-hepatitis (NASH), with or without fibrosis; as well as the development of liver fibrosis and hepatocarcinoma. The diagnosis is based on the histological findings of steatosis and inflammation of the hepatocytes, leading to their damage. Currently there is not approved therapy for NASH; and trials are being held to find the appropriate treatment and thus help decrease the burden of the disease. Genfit has developed a drug called Elafibranor. It is dual PPAR-α/δ agonist. PPARs are lipid-activated nuclear receptors. Activation of different PPARs represents an important pharmacological target because of multiple metabolic effects on carbohydrate and lipid metabolism, as well as on inflammatory response. This is a promising drug for the treatment of NASH seeing the promising results of the preclinical and clinical phases. Initial results have showed the beneficial effect of Elafibranor such as the improvement of inflammation, steatosis and fibrosis. It has also a good safety profile. The whole overall efficacy of Elafibranor in the treatment of NASh is still to be proved, and we are looking forward to the results of phase III trials to determine the future of this promising drug.

Non-alcoholic Fatty Liver Disease --- Obesity --- Liver Diseases

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Liver Diseases. --- Liver Dysfunction --- Disease, Liver --- Diseases, Liver --- Dysfunction, Liver --- Dysfunctions, Liver --- Liver Disease --- Liver Dysfunctions

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The aim of this Special Issue focusing on “Nutritional Intake and the Risk of Non-Alcoholic Fatty Liver Disease” is to provide an in-depth overview of the role of the intake of different macro- and micronutrients in the development and progression of non-alcoholic fatty liver disease, as well as in its prevention and treatment. General over-nutrition but also alterations of the dietary pattern (e.g., towards a higher intake of fat, cholesterol, and sugar—and herein especially fructose) are discussed as being critical in the development of non-alcoholic fatty liver disease (NAFLD). However, it has also been suggested that a general reduction of caloric intake and/or modulation of dietary composition, be it in regard to fat or to sugar intake, may have beneficial effects on the liver status in settings of NAFLD. Furthermore, in more recent years, the intake of pre- and probiotics, but also of specific micronutrients or secondary plant compounds, has also been considered a means in the prevention and therapy of this disease. Despite intense research efforts during the last decades, our understanding of the effects of nutritional intake on the development as well as on the prevention and cure of NAFLD is still limited. Providing a better understanding of the effects of diet and especially of specific macro- and micronutrients as well as pre- and probiotics and secondary plant compounds in the context of the development of NAFLD and its progression could lead to novel prevention and therapeutic strategies for this metabolic liver disease. This Special Issue will thus include original research and scientific perspectives on the relationship between NAFLD and dietary constituents that may 1) be involved in the development of the disease and 2) prevent its onset and progression. Mechanistic insights defining the contribution of certain nutritional factors (e.g., macronutrients like fat and sugar but also micronutrients and secondary plant compounds as well as pre- and probiotics) to the occurrence and management of NAFLD will improve our understanding of the disease and eventually lead to the development of universally accepted prevention and therapeutic strategies.

Nutrition --- Dietary pattern --- Sarkopenia --- Non-alcoholic fatty liver disease --- Diabetes and Insulin resistance

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

Medicine --- Immunology --- liver disease --- innate immunity --- myeloid-derived cells --- inflammation --- macrophage