Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development

NAFLD is the world’s most common chronic liver disease, and its increasing prevalence parallels the global rise in diabetes and obesity. It is characterised by fat accumulation in the liver evolving to non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead to liver fibrosis and cirrhosis. Currently, there is no effective pharmacotherapeutic treatment for NAFLD. Treatment is therefore based on lifestyle modifications including changes to diet and exercise, although it is unclear what the most effective form of intervention is. The aim of this review, then, is to discuss the role of specific nutrients and the effects of different dietary interventions on NAFLD. It is well established that an unhealthy diet rich in calories, sugars, and saturated fats and low in polyunsaturated fatty acids, fibre, and micronutrients plays a critical role in the development and progression of this disease. However, few clinical trials have evaluated the effects of nutrition interventions on NAFLD. We, therefore, summarise what is currently known about the effects of macronutrients, foods, and dietary patterns on NAFLD prevention and treatment. Most current guidelines recommend low-calorie, plant-based diets, such as the Mediterranean diet, as the most effective dietary pattern to treat NAFLD. More clinical trials are required, however, to identify the best evidence-based dietary treatment approach.     

The role of diet and nutrient composition in nonalcoholic Fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world. NAFLD is tightly linked to insulin resistance and considered to be the hepatic manifestation of the metabolic syndrome. The cornerstone of any treatment regimen for patients with NAFLD is lifestyle modification focused on weight loss, exercise, and improving insulin sensitivity. Here we review the literature and discuss the role of diet and nutrient composition in the management of NAFLD. Because there are currently no specific dietary guidelines for NAFLD, this review proposes a dietary framework for patients with NAFLD based on the available evidence and extrapolates from dietary guidelines aimed at reducing insulin resistance and cardiovascular risk.     

Beyond the Paradigm of Weight Loss in Non-Alcoholic Fatty Liver Disease: From Pathophysiology to Novel Dietary Approaches

Current treatment recommendations for non-alcoholic fatty liver disease (NAFLD) rely heavily on lifestyle interventions. The Mediterranean diet and physical activity, aiming at weight loss, have shown good results in achieving an improvement of this liver disease. However, concerns related to compliance and food accessibility limit the feasibility of this approach, and data on the long-term effects on liver-related outcomes are lacking. Insulin resistance is a central aspect in the pathophysiology of NAFLD; therefore, interventions aiming at the improvement of insulin sensitivity may be preferable. In this literature review, we provide a comprehensive summary of the available evidence on nutritional approaches in the management of NAFLD, involving low-calorie diets, isocaloric diets, and the novel schemes of intermittent fasting. In addition, we explore the harmful role of single nutrients on liver-specific key metabolic pathways, the role of gene susceptibility and microbiota, and behavioral aspects that may impact liver disease and are often underreported in clinical setting. At present, the high variability in terms of study populations and liver-specific outcomes within nutritional studies limits the generalizability of the results and highlights the urgent need of a tailored and standardized approach, as seen in regulatory trials in Non-Alcoholic Steatohepatitis (NASH).     

Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis

Pharmacological treatment modalities for non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are scarce, and discoveries are challenged by lack of predictive animal models adequately reflecting severe human disease stages and co-morbidities such as obesity and type 2 diabetes. To mimic human NAFLD/NASH etiology, many preclinical models rely on specific dietary components, though metabolism may differ considerably between species, potentially affecting outcomes and limiting comparability between studies. Consequently, understanding the physiological effects of dietary components is critical for high translational validity. This study investigated the effects of high fat, cholesterol, and carbohydrate sources on NASH development and metabolic outcomes in guinea pigs. Diet groups (n = 8/group) included: low-fat low-starch (LF-LSt), low-fat high-starch (LF-HSt), high-fat (HF) or HF with 4.2%, or 8.4% sugar water supplementation. The results showed that caloric compensation in HF animals supplied with sugar water led to reduced feed intake and a milder NASH phenotype compared to HF. The HF group displayed advanced NASH, weight gain and glucose intolerance compared to LF-LSt animals, but not LF-HSt, indicating an undesirable effect of starch in the control diet. Our findings support the HF guinea pig as a model of advanced NASH and highlights the importance in considering carbohydrate sources in preclinical studies of NAFLD.     

Quelle alimentation proposer aux patients présentant une stéatohépatite non-alcoolique ?

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a quarter of the world's population, some of whom will progress to a more severe form called non-alcoholic steatohepatitis (NASH). The main factor leading to this condition is an unbalanced diet. No drug treatment is approved to date and only dietary management can improve the histological lesions of NASH through weight loss. However, the efficacy of standard diets, patient compliance and the ability to maintain weight loss over the long term are common difficulties. In this review, we analyze recent scientific data on different types of diet (Mediterranean diet, intermittent fasting, ketogenic diet), which can bring benefits on general and liver health. Drawbacks or limitations are also listed. The possible benefit of other nutritional strategies (coffee consumption, omega-3, polyphenols…) is discussed. The value of dietary change could be tailored to the patient's needs without necessarily imposing an intense weight loss.     

Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)

Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD.     

Temporal Development of Dyslipidemia and Nonalcoholic Fatty Liver Disease (NAFLD) in Syrian Hamsters Fed a High-Fat,High-Fructose,High-Cholesterol Diet

The use of translationally relevant animal models is essential, also within the field of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Compared to frequently used mouse and rat models, the hamster may provide a higher degree of physiological similarity to humans in terms of lipid profile and lipoprotein metabolism. However, the effects in hamsters after long-term exposure to a NASH diet are not known. Male Syrian hamsters were fed either a high-fat, high-fructose, high-cholesterol diet (NASH diet) or control diets for up to 12 months. Plasma parameters were assessed at two weeks, one, four, eight and 12 months and liver histopathology and biochemistry was characterized after four, eight and 12 months on the experimental diets. After two weeks, hamsters on NASH diet had developed marked dyslipidemia, which persisted for the remainder of the study. Hepatic steatosis was present in NASH-fed hamsters after four months, and hepatic stellate cell activation and fibrosis was observed within four to eight months, respectively, in agreement with progression towards NASH. In summary, we demonstrate that hamsters rapidly develop dyslipidemia when fed a high-fat, high-fructose, high-cholesterol diet. Moreover, within four to eight months, the NASH-diet induced hepatic changes with resemblance to human NAFLD.     

Supplementation with a Specific Combination of Metabolic Cofactors Ameliorates Non-Alcoholic Fatty Liver Disease,Hepatic Fibrosis,and Insulin Resistance in Mice

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have emerged as the leading causes of chronic liver disease in the world. Obesity, insulin resistance, and dyslipidemia are multifactorial risk factors strongly associated with NAFLD/NASH. Here, a specific combination of metabolic cofactors (a multi-ingredient; MI) containing precursors of glutathione (GSH) and nicotinamide adenine dinucleotide (NAD⁺) (betaine, N-acetyl-cysteine, L-carnitine and nicotinamide riboside) was evaluated as effective treatment for the NAFLD/NASH pathophysiology. Six-week-old male mice were randomly divided into control diet animals and animals exposed to a high fat and high fructose/sucrose diet to induce NAFLD. After 16 weeks, diet-induced NAFLD mice were distributed into two groups, treated with the vehicle (HFHFr group) or with a combination of metabolic cofactors (MI group) for 4 additional weeks, and blood and liver were obtained from all animals for biochemical, histological, and molecular analysis. The MI treatment reduced liver steatosis, decreasing liver weight and hepatic lipid content, and liver injury, as evidenced by a pronounced decrease in serum levels of liver transaminases. Moreover, animals supplemented with the MI cocktail showed a reduction in the gene expression of some proinflammatory cytokines when compared with their HFHFr counterparts. In addition, MI supplementation was effective in decreasing hepatic fibrosis and improving insulin sensitivity, as observed by histological analysis, as well as a reduction in fibrotic gene expression (Col1α1) and improved Akt activation, respectively. Taken together, supplementation with this specific combination of metabolic cofactors ameliorates several features of NAFLD, highlighting this treatment as a potential efficient therapy against this disease in humans.     

Mediterranean diet and nonalcoholic fatty liver disease: molecular mechanisms of protection

Nutritional habits modifications have shown an important impact in preventing and ameliorating metabolic alterations, such as nonalcoholic fatty liver disease (NAFLD). Among several dietary approaches that exert positive effects in NAFLD patients, the Mediterranean dietary pattern has shown notable benefits. This review explores the molecular mechanisms through which the Mediterranean diet would improve risk factors associated with metabolic syndrome and NAFLD. The main features of the Mediterranean diet acting on metabolism are represented by its whole-grain and low glycemic index cereal-based items, its fatty acid profile, and its content in phytochemical compounds. Carbohydrate-rich foods high in dietary fiber inducing low glycemic response are able to interact with glucose and insulin metabolism. Unsaturated fatty acids are associated with better hepatic lipid metabolism. Finally, phytochemical compounds, such as dietary polyphenols, are thought to ameliorate inflammation, which is considered one of the mechanisms through which NALFD may evolve into nonalcoholic steatohepatitis (NASH).     

Place de l’Activité Physique Adaptée dans le parcours de soins : cas du patient présentant une stéatose hépatique non-alcoolique (NAFLD)

Non-Alcoholic Fatty Liver Disease (NAFLD) is estimated to affect 26% of men and 11% of women in France. NAFLD is a continuum of liver damage ranging from, simple steatosis, to non-alcoholic steatohepatitis (NASH), NASH with liver fibrosis and sometimes post-NASH cirrhosis. NAFLD is favored by excess weight (overweight or obesity) associated with systemic metabolic abnormalities affecting particularly, adipose tissue and striated muscles. The preventive and curative treatment of NAFLD is based on hygienic and dietary measures. These measures have proven to be effective in terms of resolution of NASH and stabilization or even regression of liver fibrosis. The implementation of a program of adapted physical activity (APA), by a competent professional, contributes significantly to the improvement of the clinical state independently of weight loss. At the molecular level, the current literature emphazises the pleiotropic effect of this management, particularly through its direct or indirect action on local (e.g. hepatic) and systemic metabolism, the systemic inflammatory state and rheological activity. Beyond these pathophysiological repercussions, the APA professional accompanies the patient with a chronic disease, in this case NAFLD, to induce a sustainable lifestyle change by focusing on his or her motivational state. These measures appear to be beneficial for both adults and children.     

La stéatopathie dysmétabolique ou NASH : faut-il dépister les patients à haut risque atteints de diabète de type 2 ou d’obésité ?

Nonalcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. It encompasses a spectrum of phenotypes including benign hepatic steatosis (NAFL) and nonalcoholic steatohepatitis (NASH) which is considered as the progressive form with higher risk of progression towards liver fibrosis, cirrhosis or hepatocellular carcinoma. NAFLD remains asymptomatic until end-stage of the disease and is largely underdiagnosed. In the last decades, populations at high risk of progression to advanced fibrosis, such as obese and type 2 diabetic (T2D) patients, have been identified. The presence of advanced fibrosis has been identified as the major determinant of overall and hepatic mortality. Liver biopsy remains the gold standard for the diagnosis of NASH and hepatic fibrosis, however several noninvasive blood-based and imaging-based biomarkers have been developed for the assessment and screening for liver fibrosis. Finally, the lifestyle modification and weight loss intervention improve steatosis, NASH and liver fibrosis, and therapeutic clinical trials for the treatment of NASH are an area of intensive research. This review article will summarize the current evidence supporting the systematic screening for advanced fibrosis in high-risk population such as T2D and obese patients. Several modalities are available for such screening. However, additional studies are needed to determine the optimal strategy for a systematic screening in high risk population and to allow efficient and cost-effectiveness pathway referral in hepatology clinics.     

Nonalcoholic fatty liver disease: a review of the spectrum of disease, diagnosis, and therapy

Worldwide, there is an epidemic of obesity and overweight, with two-thirds of Americans affected. A strong association exists between excessive body weight and nonalcoholic fatty liver disease (NAFLD), the most common etiology of abnormal liver function tests. Nonalcoholic fatty liver disease is a spectrum of liver disease, from a "bland" fatty infiltration to chronic hepatitis (nonalcoholic steatohepatitis or NASH), that can result in cirrhosis and organ failure. With the increasing prevalence of obesity in the world, the proportion of people affected by NAFLD is only expected to be parallel. Although primarily noted in obese individuals, NAFLD has also been associated with a number of surgical procedures, metabolic conditions, and medications. NASH is commonly underdiagnosed as most affected patients are symptom free, and routine screening is not performed. Noninvasive diagnostic testing is not sensitive in diagnosis or staging the severity of disease. Fatty infiltration and oxidative injury to the hepatocytes are believed to be the major factors behind the progression of disease from simple fatty infiltration of the liver to chronic hepatitis. Understanding the inflammatory pathways involved in NASH is a subject of extensive research. Currently, few proven treatment options exist, and controlled weight reduction is the only safe modality recommended for treatment of NASH.     

Mega-Dose Vitamin C Ameliorates Nonalcoholic Fatty Liver Disease in a Mouse Fast-Food Diet Model

In previous studies, the increasing clinical importance of nonalcoholic fatty liver disease (NAFLD) has been recognized. However, the specific therapeutic strategies or drugs have not been discovered. Vitamin C is a water-soluble antioxidant and is a cofactor in many important biosynthesis pathways. Recently, many researchers have reported that the mega-dose vitamin C treatment had positive effects on various diseases. However, the precise relationship between mega-dose vitamin C and NAFLD has not been completely elucidated. This study has been designed to discover the effects of mega-dose vitamin C on the progression of NAFLD. Twelve-week-old wild-type C57BL6 mice were fed chow diets and high-fat and high-fructose diet (fast-food diet) ad libitum for 11 weeks with or without of vitamin C treatment. Vitamin C was administered in the drinking water (1.5 g/L). In this study, 11 weeks of the mega-dose vitamin C treatment significantly suppressed the development of nonalcoholic steatohepatitis (NASH) independently of the catabolic process. Vitamin C supplements in fast-food diet fed mice significantly decreased diet ingestion and increased water intake. Histopathological analysis revealed that the mice fed a fast-food diet with vitamin C water had a mild renal injury suggesting osmotic nephrosis due to fructose-mediated purine derivatives. These data suggest that the mega-dose vitamin C treatment suppresses high-fructose-diet-mediated NAFLD progression by decreasing diet ingestion and increasing water intake.     

Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD) has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.     

Metabolic-Associated Fatty Liver Disease (MAFLD), Diabetes,and Cardiovascular Disease: Associations with Fructose Metabolism and Gut Microbiota

Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition associated with type 2 diabetes (T2DM) and cardiovascular disease (CVD). Since systemic metabolic dysfunction underlies NAFLD, the current nomenclature has been revised, and the term metabolic-associated fatty liver disease (MAFLD) has been proposed. The new definition emphasizes the bidirectional relationships and increases awareness in looking for fatty liver disease among patients with T2DM and CVD or its risk factors, as well as looking for these diseases among patients with NAFLD. The most recommended treatment method of NAFLD is lifestyle changes, including dietary fructose limitation, although other treatment methods of NAFLD have recently emerged and are being studied. Given the focus on the liver–gut axis targeting, bacteria may also be a future aim of NAFLD treatment given the microbiome signatures discriminating healthy individuals from those with NAFLD. In this review article, we will provide an overview of the associations of fructose consumption, gut microbiota, diabetes, and CVD in patients with NAFLD.     

Update on non-alcoholic fatty liver disease in children

Non-alcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the pediatric community. It is closely associated with obesity and insulin resistance. NAFLD may lead to non-alcoholic steatohepatitis (NASH). Although NASH is a prerequisite for the definition of NAFLD in adults and children, distinct differences are often apparent in the extent or location of fat, inflammation and fibrosis. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to summarize what is known about pediatric NAFLD in terms of prevalence, pathogenesis, diagnosis, histology and treatment.     

Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis.     

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.     

Nonalcoholic fatty liver disease: the potential role of nutritional management

PURPOSE OF REVIEW: To review available data pertaining to dietary imbalances and metabolic alterations leading to the development of fatty liver disease and nutritional managements. RECENT FINDINGS: The importance of treating fatty liver disease is now firmly recognized not only because of the risk of progression toward a more aggressive liver disease but also because the fatty liver is an important provider of cardiovascular risks. The ideal diet for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis patients should reduce fat mass and inflammation in the adipose tissue, restore insulin sensitivity, and provide low amounts of substrates for de-novo lipogenesis, but scientific evidence to recommend specific diets is currently lacking. Moderate weight loss, low-calorie diets, reduction in saturated fatty acids intake, together with an increase in monosaturated and n-3 polyunsaturated fatty acids appear to be beneficial. Excessive consumption of high glycemic index carbohydrates appears deleterious, as it favors hyperglycemia and hyperinsulinemia and stimulates de-novo lipogenesis. Physical exercise is an important component of the approach, as it improves insulin sensitivity. Behavioral therapy promotes long-term compliance to lifestyle modifications. SUMMARY: One panacea is unlikely to be found, the more useful approach is probably multimodal and includes tailored lifestyle modifications. Randomized controlled trials are needed to establish dietary recommendations. While awaiting such trials, reduced consumption of simple sugar, especially sweetened beverages, and incremental increase in physical activity must be encouraged.