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1.
Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease.
Valenti, L, Pedica, F, Colombo, M
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver. 2022;(2):154-163
Abstract
Hepatocellular carcinoma (HCC) is on the rise globally, causing more than 800 thousand deaths annually, with an estimated annual percent change of 0.51 for causes other than viral hepatitis, including nonalcoholic fatty liver disease (NAFLD). The incidence of NAFLD-related HCC is peaking in several Far East regions (6-12% vs. 2-3% in Western Europe and USA), HCC risk being mainly driven by the epidemic of obesity and diabetes, both favored by an unhealthy diet and sedentary lifestyle. Under inherited susceptibility outlined by such genetic markers as variants in PNPLA3, TM6SF2 and MBOAT7, neoplastic transformation of NAFLD is driven by sublethal lipotoxicity consequent to hepatocyte lipid overload, whereas a myriad of factors spanning from subverted circadian homeostasis and gut dysbiosis to alcohol abuse and tobacco may interact as risk modifiers. At variance with viral HCC, NAFLD-HCC shows a frequent association with cardiovascular co-morbidities, absence of cirrhosis in up to half of patients and an association with persistently normal transaminase values. All these misleading features of NAFLD-related HCC account for the low uptake of surveillance and linkage to curative treatments that has been reported in patients with this cancer, a downside that could be attenuated when scores for cost-effective risk stratification become available.
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2.
Fit mothers for a healthy future: Breaking the intergenerational cycle of non-alcoholic fatty liver disease with maternal exercise.
Stevanović-Silva, J, Beleza, J, Coxito, P, Costa, RC, Ascensão, A, Magalhães, J
European journal of clinical investigation. 2022;(3):e13596
Abstract
UNLABELLED SPECIAL ISSUE 'FOIEGRAS-Bioenergetic Remodelling in the Pathophysiology and Treatment of Non-Alcoholic Fatty Liver Disease'. BACKGROUND Non-alcoholic fatty liver disease (NAFLD) emerges as significant health burden worldwide. Lifestyle changes, unhealthy dietary habits and physical inactivity, can trigger NAFLD development. Persisting on these habits during pregnancy affects in utero environment and prompts a specific metabolic response in foetus resulting in offspring metabolic maladjustments potentially critical for developing NAFLD later in life. The increasing prevalence of NAFLD, particularly in children, has shifted the research focus towards preventive and therapeutic strategies. Yet, designing effective approaches that can break the NAFLD intergenerational cycle becomes even more complicated. Regular physical exercise (PE) is a powerful non-pharmacological strategy known to counteract deleterious metabolic outcomes. In this narrative review, we aimed to briefly describe NAFLD pathogenesis focusing on maternal nutritional challenge and foetal programming, and to provide potential mechanisms behind the putative intergenerational effect of PE against metabolic diseases, including liver diseases. METHODS Following detailed electronic database search, recent existing evidence about NAFLD development, intergenerational programming and gestational exercise effects was critically analysed and discussed. RESULTS PE during pregnancy could have a great potential to counteract intergenerational transmission of metabolic burden. The interplay between different PE roles-metabolic, endocrine and epigenetic-could offer a more stable in utero environment to the foetus, thus rescuing offspring vulnerability to metabolic disturbances. CONCLUSIONS The better understanding of maternal PE beneficial consequences on offspring metabolism could reinforce the importance of PE during pregnancy as an indispensable strategy in improving offspring health.
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3.
Is there an 'ideal' diet for patients with NAFLD?
Pugliese, N, Plaz Torres, MC, Petta, S, Valenti, L, Giannini, EG, Aghemo, A
European journal of clinical investigation. 2022;(3):e13659
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic that encompasses three distinct clinical phenotypes: uncomplicated fatty liver, nonalcoholic steatohepatitis (NASH) and NASH-related cirrhosis with its complications, including hepatocellular carcinoma. To date, no pharmacological treatments have been approved and lifestyle modifications including reduced caloric intake targeting a 7%-10% weight loss from baseline assessment represent the standard approach. Mediterranean diet has been recommended as the best dietary pattern since it is easy to follow and, independently of caloric intake its nutritional components have beneficial metabolic effects that not only improve steatosis but also risk factors for cardiovascular events, the leading cause of morbidity/mortality in individuals with NAFLD. Other dietary patterns such as ketogenic diet and Dietary Approach to Stop Hypertension (DASH) diet can be used in patients with NAFLD. Recently, intermittent fasting diets have gained popularity among healthy individuals and have been proposed as a safe and effective treatment for the metabolic syndrome in experimental and in a few human studies. In this narrative review, we aim to summarize the evidence for the available dietary approaches for patients with NAFLD.
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4.
Role of the mTOR-autophagy-ER stress pathway in high fructose-induced metabolic-associated fatty liver disease.
Wang, YL, Zhou, X, Li, DL, Ye, JM
Acta pharmacologica Sinica. 2022;(1):10-14
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Abstract
Metabolic-associated fatty liver disease (MAFLD) is the most common metabolic disease with a global prevalence of 25%. While MAFLD is serious and incurable at the later stage, it can be controlled or reversed at the early stage of hepatosteatosis originating from unhealthy diets. Recent laboratory evidence implicates a critical role of the mammalian target of rapamycin (mTOR)-autophagy signaling pathway in the pathogenesis of MAFLD induced by a high-fructose diet mimicking the overconsumption of sugar in humans. This review discusses the possible molecular mechanisms of mTOR-autophagy-endoplasmic reticulum (ER) stress in MAFLD. Based on careful analysis of recent studies, we suggest possible new therapeutic concepts or targets that can be explored for the discovery of new anti-MAFLD drugs.
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The role of nutrition in non-alcoholic fatty liver disease treatment in obese children.
Guimber, D, Debray, D, Bocquet, A, Briend, A, Chouraqui, JP, Darmaun, D, Feillet, F, Frelut, ML, Hankard, R, Lapillonne, A, et al
Archives de pediatrie : organe officiel de la Societe francaise de pediatrie. 2022;(1):1-11
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease that occurs mostly in the context of insulin resistance and obesity. It has rapidly evolved into the most common cause of liver disease among children. The incidence is high in obese children and a greater risk of disease progression is associated with severe obesity, highlighting the role of nutrition. To date, there is no consensus on NAFLD management. This is a narrative review of clinical studies on the potential benefit of nutritional interventions, including lifestyle modifications, vitamins, docosahexaenoic acid, and probiotics in children with NAFLD. The Comité de nutrition de la Société Française de Pédiatrie (CN-SFP) emphasizes the effect of limiting added sugar intake, i.e., fructose or sucrose-containing beverages, and promoting physical activity in the care of NAFLD.
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Adipose tissue insulin resistance and lipidome alterations as the characterizing factors of non-alcoholic steatohepatitis.
Guerra, S, Mocciaro, G, Gastaldelli, A
European journal of clinical investigation. 2022;(3):e13695
Abstract
BACKGROUND The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe forms, that is non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma leading to death. METHODS In this narrative review, we have discussed the current knowledge in the pathophysiology of fatty liver disease, including both metabolic and non-metabolic factors, insulin resistance, mitochondrial function, as well as the markers of liver damage, giving attention to the alterations in lipid metabolism and production of lipotoxic lipids. RESULTS Insulin resistance, particularly in the adipose tissue, is the main driver of NAFLD due to the excess release of fatty acids. Lipidome analyses have shown that several lipids, including DAGs and ceramides, and especially if they contain saturated lipids, act as bioactive compounds, toxic to the cells. Lipids can also affect mitochondrial function. Not only lipids, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, as branched-chain and aromatic amino acids, glutamate, serine and glycine, have been linked to impaired metabolism, insulin resistance and severity of NAFLD and serine is a precursor of ceramides. CONCLUSIONS The measurement of lipotoxic species and adipose tissue dysfunction can help to identify individuals at risk of progression to NASH.
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The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.
Robeva, R, Mladenović, D, Vesković, M, Hrnčić, D, Bjekić-Macut, J, Stanojlović, O, Livadas, S, Yildiz, BO, Macut, D
Maturitas. 2021;:22-30
Abstract
The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.
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Defining comprehensive models of care for NAFLD.
Lazarus, JV, Anstee, QM, Hagström, H, Cusi, K, Cortez-Pinto, H, Mark, HE, Roden, M, Tsochatzis, EA, Wong, VW, Younossi, ZM, et al
Nature reviews. Gastroenterology & hepatology. 2021;(10):717-729
Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease globally. Despite the increased demand placed on health-care systems, little attention has been given to the design and implementation of efficient and effective models of care for patients with NAFLD. In many health-care settings, no formal pathways exist and, where pathways are in place, they are often not standardized according to good practices. We systematically searched the peer-reviewed literature with the aim of identifying published examples of comprehensive models of care that answered four key questions: what services are provided? Where are they provided? Who is offering them? How are they coordinated and integrated within health-care systems? We identified seven models of care and synthesized the findings into eight recommendations nested within the 'what, where, who and how' of care models. These recommendations, aimed at policy-makers and practitioners designing and implementing models of care, can help to address the increasing need for the provision of good practice care for patients with NAFLD.
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Efficacy of Dietary Manipulations for Depleting Intrahepatic Triglyceride Content: Implications for the Management of Non-alcoholic Fatty Liver Disease.
Sandby, K, Geiker, NRW, Dalamaga, M, Grønbæk, H, Magkos, F
Current obesity reports. 2021;(2):125-133
Abstract
PURPOSE OF REVIEW Understanding the effects of dietary manipulations on intrahepatic triglyceride (IHTG) balance will have important implications for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). RECENT FINDINGS Reducing calorie intake to induce weight loss is the most potent intervention to decrease IHTG. Carbohydrate restriction during the initial stages of weight loss may be particularly beneficial, but at later stages, the amount of weight loss predominates over diet composition. By contrast, during weight stability, restricting calories from fat seems to be optimal for depleting liver fat. The degree of dietary fat saturation and the glycemic index of the carbohydrate have inconsistent effects on IHTG. Recently, the matrix of some foods (e.g., dairy) has been inversely associated with NAFLD. Dietary macronutrients differ in their effects on liver fat depending on the energy balance and the matrix of the food in which they are consumed. Therefore, investigations into dietary approaches for managing NAFLD should shift their perspective from that of isolated nutrients to that of whole foods and diets and include useful mechanistic insights.
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Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology.
Della Torre, S
Cells. 2021;(9)
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.