Background and Objectives: The prevalence of pediatric non-alcoholic fatty liver disease is increasing. A lot of new data are published regularly. Materials and Methods: Original clinical studies, review articles, and guidelines in children were searched for and the most relevant included in this review. Results: A total of 138 retrieved papers were classified into pathogenesis, epidemiology, diagnosis, and treatment. Pathogenesis is currently explained with the "multi hit hypothesis", with complex interactions of genetic and environmental factors which trigger inflammation in steatotic liver. The prevalence is rising. A diagnosis can be made with laboratory tests, imaging, and liver biopsy after the exclusion of other causes of liver steatosis. The mainstay of treatment is lifestyle modification consisting of dietary intervention and increased physical activity. The progression to liver cirrhosis can occur even in children. Conclusions: Non-alcoholic fatty liver disease in children is a part of a metabolic syndrome in the majority of patients. Due to its complex etiology and high prevalence, multidisciplinary teams, together with public health professionals, should be involved in its treatment.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. It occurs with a prevalence of up to 25%, of which 10-20% cases progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. The histopathology of NASH is characterized by neutrophilic infiltration, and endotoxins from gram-negative rods have been postulated as a contributing factor. Elevations in endotoxin levels in the blood can be classified as intestinal and hepatic factors. In recent years, leaky gut syndrome, which is characterized by impaired intestinal barrier function, has become a significant issue. A leaky gut may prompt intestinal bacteria dysbiosis and increase the amount of endotoxin that enters the liver from the portal vein. These contribute to persistent chronic inflammation and progressive liver damage. In addition, hepatic factors suggest that liver damage can be induced by low-dose endotoxins, which does not occur in healthy individuals. In particular, increased expression of CD14, an endotoxin co-receptor in the liver, may result in leptin-induced endotoxin hyper-responsiveness in obese individuals. Thus, elevated blood endotoxin levels contribute to the progression of NASH. The current therapeutic targets for NASH treat steatosis and liver inflammation and fibrosis. While many clinical trials are underway, no studies have been performed on therapeutic agents that target the intestinal barrier. Recently, a randomized placebo-controlled trial examined the role of the intestinal barrier in patients with NAFLD. To our knowledge, this study was the first of its kind and study suggested that the intestinal barrier may be a novel target in the future treatment of NAFLD.

For the detection of steatosis, quantitative ultrasound imaging techniques have achieved great progress in past years. Magnetic resonance imaging proton density fat fraction is currently the most accurate test to detect hepatic steatosis. Some blood biomarkers correlate with non-alcoholic steatohepatitis, but the accuracy is modest. Regarding liver fibrosis, liver stiffness measurement by transient elastography (TE) has high accuracy and is widely used across the world. Magnetic resonance elastography is marginally better than TE but is limited by its cost and availability. Several blood biomarkers of fibrosis have been used in clinical trials and hold promise for selecting patients for treatment and monitoring treatment response. This article reviews new developments in the non-invasive assessment of non-alcoholic fatty liver disease (NAFLD). Accumulating evidence suggests that various non-invasive tests can be used to diagnose NAFLD, assess its severity, and predict the prognosis. Further studies are needed to determine the role of the tests as monitoring tools. We cannot overemphasize the importance of context in selecting appropriate tests.

Non-alcoholic fatty liver disease (NAFLD) has become the most frequently encountered chronic liver disease. NAFLD is associated with increased liver-related morbidity and mortality, but also contributes to cardiovascular disease, diabetes and non-liver-related malignancy. Non-alcoholic steatohepatitis (NASH) is considered the more severe subtype of NAFLD that drives most of these adverse outcomes. Lifestyle modification and associated weight loss can improve NASH but are not always sufficient and sustained results are difficult to obtain. There is hence an urgent need for pharmacological treatment. In this review we discuss some of the concepts and challenges in the development of pharmacological treatment. We also briefly summarise what can be achieved with some of the drugs that are currently available for other indications but have demonstrated benefit in the treatment of NASH. Finally we present an overview of some of the main drugs or types of drugs, mainly based on their mode of action, that are now being developed specifically to treat NASH and that might soon result in the availability of drugs licensed for NASH.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

This patient guideline is intended for all patients at risk of or living with non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent chronic liver disease worldwide and comes with a high disease burden. Yet, there is a lot of unawareness. Furthermore, many aspects of the disease are still to be unravelled, which has an important impact on the information that is given (or not) to patients. Its management requires a close interaction between patients and their many healthcare providers. It is important for patients to develop a full understanding of NAFLD in order to enable them to take an active role in their disease management. This guide summarises the current knowledge relevant to NAFLD and its management. It has been developed by patients, patient representatives, clinicians and scientists and is based on current scientific recommendations, intended to support patients in making informed decisions.

Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease, and it is associated with numerous extra-hepatic manifestations or additional co-occurring diseases. The aim of the present review was the identification and management of the hematologic manifestations of NAFLD. One of the triggers is considered to be iron abnormalities. Increased ferritin levels, hepatic iron deposits and iron overload are associated with NAFLD. The iron overload degree and severity are associated with the level of liver fibrosis and with the risk for hepatocellular carcinoma. Excess iron deposits refers to the dysmetabolic iron overload syndrome (DIOS) and it is characterized by steatosis associated with moderate tissue iron deposition and increased levels of serum ferritin, while the serum transferrin saturation was normal. Further prospective studies are necessary to determine whether NAFLD has an independent risk for hematologic symptoms, besides the known risk factors. Future studies are also needed in order to assess the increasing impact of NAFLD on the micro- and macro-vascular complications of this systemic disease.

In non-alcoholic steatohepatitis (NASH), the function of urea cycle enzymes (UCEs) may be affected, resulting in hyperammonemia and the risk of disease progression. We aimed to determine whether the expression and function of UCEs are altered in an animal model of NASH and in patients with non-alcoholic fatty liver disease (NAFLD), and whether this process is reversible.

Background: Adolescent non-alcoholic fatty liver disease (NAFLD) is associated with cardiometabolic risk factors. The association between adolescent NAFLD and a wide range of metabolic biomarkers is unclear. We have attempted to determine the differences in metabolic profile of adolescents with and without markers of NAFLD. Methods: We performed cross-sectional analyses in a sample of 3,048 participants from the Avon Longitudinal Study of Parents and Children at age 17. We used three indicators of NAFLD: ALT >40 U/l; AST >40 U/l and ultrasound scan-assessed steatosis. Associations between each measure of NAFLD and 154 metabolic traits, assessed by Nuclear Magnetic Resonance, were analyzed by multivariable linear regression, adjusting for age, sex and BMI. Results: All three indicators of NAFLD were associated with ~0.5 standard deviation (SD) greater concentrations of all extremely large to small very low-density lipoproteins (VLDL) measures. ALT >40U/l was associated with ~0.5SD greater concentrations of very small VLDLs, intermediate-density lipoproteins and low-density lipoproteins. Concentrations of most cholesterols, including remnant cholesterol, all triglycerides and monounsaturated fatty acids, in addition to glycoprotein acetyls (inflammatory marker), were also higher in participants with NAFLD. Conclusions: We have identified differing metabolic profiles between adolescents with and without indicators of NAFLD. These results provide the foundations for future research to determine whether these differences persist and result in adverse future cardiometabolic health.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with obesity and may progress to non-alcoholic steatohepatitis (NASH) and liver fibrosis. The deficit of pharmacological therapies for the latter mainly results from an incomplete understanding of involved pathological mechanisms. Herein, we identify apoptosis signal-regulating kinase 1 (ASK1) as a suppressor of NASH and fibrosis formation. High-fat diet-fed and aged chow-fed liver-specific ASK1-knockout mice develop a higher degree of hepatic steatosis, inflammation, and fibrosis compared to controls. In addition, pharmacological inhibition of ASK1 increased hepatic lipid accumulation in wild-type mice. In line, liver-specific ASK1 overexpression protected mice from the development of high-fat diet-induced hepatic steatosis and carbon tetrachloride-induced fibrosis. Mechanistically, ASK1 depletion blunts autophagy, thereby enhancing lipid droplet accumulation and liver fibrosis. In human livers of lean and obese subjects, ASK1 expression correlated negatively with liver fat content and NASH scores, but positively with markers for autophagy. Taken together, ASK1 may be a novel therapeutic target to tackle NAFLD and liver fibrosis.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD.

Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple hepatic steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which may progress to cirrhosis and liver cancer. NAFLD is rapidly becoming a global health challenge, and there is a need for improved diagnostic- and prognostic tools and for effective pharmacotherapies to treat NASH. The molecular mechanisms of NAFLD development and progression remain incompletely understood, though ample evidence supports a role of microRNAs (miRNAs) - small non-coding RNAs regulating gene expression - in the progression of metabolic liver disease.

Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States and globally. The currently understood model of pathogenesis consists of a 'multiple hit' hypothesis in which environmental and genetic factors contribute to hepatic inflammation and injury.

Although sarcopenia is known to be a risk factor for non-alcoholic fatty liver disease (NAFLD), whether NAFLD is a risk factor for the development of sarcopenia is not clear. We investigated relationships between NAFLD and low skeletal muscle mass index (LSMI) using three different datasets. Participants were classified into LSMI and normal groups. LSMI was defined as a body mass index (BMI)-adjusted appendicular skeletal muscle mass <0.789 in men and <0.512 in women or as the sex-specific lowest quintile of BMI-adjusted total skeletal muscle mass. NAFLD was determined according to NAFLD liver fat score or abdominal ultrasonography. The NAFLD groups showed a higher hazard ratios (HRs) with 95% confidence intervals (CIs) for LSMI than the normal groups (HRs = 1.21, 95% CIs = 1.05-1.40). The LSMI groups also showed a higher HRs with 95% CIs for NAFLD than normal groups (HRs = 1.56, 95% CIs = 1.38-1.78). Participants with NAFLD had consistently less skeletal muscle mass over 12 years of follow-up. In conclusion, LSMI and NAFLD showed a relationship. Maintaining muscle mass should be emphasized in the management of NAFLD.

The accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.

Danshao Shugan Granules (DSSG), a traditional Chinese medicine (TCM), is given to protect the liver. The objective is to evaluate the mechanisms of the effects of DSSG on non-alcoholic fatty liver disease (NAFLD).

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent cause of liver disease in Western countries. The development of non-alcoholic steatohepatitis (NASH) and fibrosis identifies an at-risk group with increased risk of cardiovascular and liver-related deaths. The identification and management of this at-risk group remains a clinical challenge.

Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data.