The discovery, probiotic properties, and genome analysis of Lactiplantibacillus plantarum HP-B1280 with potential therapeutic application for the treatment of non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder, is diagnosed and managed not only by both pediatric gastroenterologists/hepatologists but also frequently by the general pediatrician. This article updates recent advances in diagnostic and therapeutic approach, which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the pediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical, and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach, but the compliance is poor and pharmacological treatment would be helpful; docosahexaenoic acid, some probiotics, and vitamin E are to be considered, but evidence is not sufficient to recommend widespread use.

Non-alcoholic fatty liver disease (NAFLD) is defined as the abnormal accumulation of triglycerides in the liver. NAFLD has a global prevalence of almost 30%, while incidence is rising with increasing levels of obesity, type 2 diabetes mellitus (T2DM) and metabolic syndrome. Nutrition plays a significant role in both the prevention and treatment of NAFLD. Therefore, the aim of this literature review is to explore the associations between dietary, lifestyle and other risk factors and the risk for developing NAFLD. Dietary patterns, lifestyle behaviours, comorbidities, or a combination of any may contribute to either the progression or prevention of NAFLD. Having diabetes, hypertension, or having obesity might increase the progression of NAFLD if not well treated and controlled. Diet influences the progression of NAFLD; following a western diet or simply a high-fat diet may contribute to the worsening of NAFLD and further progression to non-alcoholic steatohepatitis (NASH) and cirrhosis in later stages. On the other hand, the Mediterranean diet is the gold standard for both the treatment and prevention of NAFLD. Social behaviours, such as smoking, caffeine consumption and physical activity also play a role in the pathophysiology of NAFLD. Nutrition contributes significantly to the prevention or treatment of NAFLD, since this disease can be managed by diet and physical activity. However, further studies are still needed for a better understanding of the mechanisms of action. Randomized control trials are also needed to confirm findings in observational studies.

Nonalcoholic Fatty Liver Disease in Children: Where Are We?

Nonalcoholic Fatty Liver Disease: Its Mechanisms and Complications

Objective To analyze the pathogenetic status and risk factors of nonalcoholic fatty liver disease (NAFLD) in military airerews, in order to provide evidence for the treatment and prevention of NAFLD. Methods The study included collecting data as military airerew's age, flying hours and type of aircraft, calculating body mass index (BMI), measuring liver function [alanine transaminase (ALT), aspartase aminotransferase (AST), gamma-glutamyltransferase (GGT)], fasting blood glucose (FBG), uric acid (UA), total cholesterol (TC), triglyceride(TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (HDL-C), as well as examining liver by B-ultrasound. Results were processed by variance and Logistic regression analysis according to the groups that respectively divided by NAFLD (2 groups), BMI value (2 groups) and ALT value (3 groups by the ranges within ALT<40 U/L, 40 U/L≤ALT<80 U/L and ALT≥ U/L). Results Out of 426 male aircrews, 34.98% were overweight, 19.48% had NAFLD and 16.67% were with high ALT. Compared with normal weight group, morbidity rate of NAFLD and level of ALT were significantly higher than those in over weight group (X2=145.152, 58.959, P< 0.01). Aircrews in ALT≥40 U/L group showed statistical differences on BMI and TG compared to those in ALT<40 U/L group (F=13.476, 13.176, P<0.01). ATL, AST, C, GT, TG, TC, LDL-C, FBG and UA in NAFLD group were significantly higher than those in control group (t= 2.287-7.002, P<0.05 or 0.01), but HDL-C level was significantly lower (t=2.932, P<0.01). There were no statistical differences between fast jet and low speed aircraft (transporter, bomber, helicopter, etc.) aircrews in age, flying hours, BMI and other biochemical indexes. Logistic regression analysis showed that the factors that induced NAFLD were BMI, TG and type of aircraft (Z=37.353, 8.658, 4.486, P<0.05 or 0.01). Conclusions The aircrews have higher morbidity rate of NAFLD with such high risk factors as over weight, high blood lipid (high TG, high LDL-C and low HDLC). So early diagnosis and treatment of NAFLD would be one of the most important measures for limiting its growth and preventing cardiovascular and cerebrovaseular diseases. Key words: Fatty liver; Alanine transaminase; Body mass index; Overweight; Hyperlipidemias; Factor analysis, statistical

Nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance, obesity, and other features of metabolic syndrome and is known to be the most common cause for abnormal liver enzymes. The recent surge in the number of patients with NAFLD has been accompanied by an increase in research on potential treatment options, particularly weight loss and dietary interventions. Given the growing interest on the role of carbohydrates in the prevention and treatment of NAFLD, this review discusses the relationship between the amount of carbohydrates in the diet and effects on NAFLD, with special emphasis on a low-carbohydrate diet. We discuss the role of insulin resistance in the pathophysiology of NAFLD and provide an overview of various popular diets and their role as a treatment option for NAFLD. Additional large, longer-duration trials studying the efficacy of a low-carbohydrate diet in the treatment and prevention of NAFLD are eagerly awaited.

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the United States and, indeed, worldwide. It has become a global public health issue. In the United States, the prevalence in the general population is estimated at approximately 20%, while that in the morbidly obese population at approximately 75-92% and in the pediatric population at approximately 13-14%. The progressive form of NAFLD, nonalcoholic steatohepatitis, is estimated at approximately 3-5%, with approximately 3-5% of these having progressed to cirrhosis. Thus, the numbers of individuals at risk for end-stage liver disease and development of primary liver cancer is large. NAFLD is an independent risk factor for cardiovascular disease, leads to increased all-cause mortality, and to increased liver-related mortality. This review focuses on recent advances in our understanding of the NAFLD disease spectrum, including etiology, diagnosis, treatment, and genetic and environmental risk factors and suggests future directions for research in this important area.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreatic disease (NAFPD) develop against the background of metabolic syndrome, systemic insulin resistance, oxidative stress, changes in lipid and carbohydrate metabolism. There are a number of similarities between NAFLD and NAFPD: the natural course of diseases proceeds from steatosis through inflammation to fibrosis and cancer, one of the etiopathogenetic factors is the disbalance of bile acids synthesis and low expression of farnesoid receptor X (FXR). One of the possible methods of treatment NAFLD and NAFPD is a correction of the biosynthesis of bile acids and increase FXR expression with FXR agonists. Ursodeoxycholic acid (UDCA) is a selective FXR agonist. It has a multipled spectrum of actions: anticholestatic, anti-apoptic, antioxidant, cytoprotective, antifibrotic, hypocholesterolemic, immunomodulatory, hepatoprotective. The ability of UDCA correct lipid and carbohydrate metabolism in combination with anti-inflammatory and antiapoptic effects may be of great importance for the treatment of NAFLD and NAFPD. The article reviews the results of clinical and experimental studies describing the efficacy of UDCA in NAFLD and some pancreatic diseases. It has been suggested that the therapy of UDCA can reduce the severity of NAFLD and NAFPDand improve the functional activity of hepatocytes and β cells. The need for randomized clinical trials was emphasized in order to make an informed decision on the expediency of including UDCA in the treatment of NAFLD and NAFPD.

Shedding new light on vitamin D and fatty liver disease

Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level. Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics. Results: SLBZS intervention for 6weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS. Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

Chinese herbal medicines: The modulator of nonalcoholic fatty liver disease targeting oxidative stress

Objective To investigate the efficacy of different doses of vitamin C (VC) in prevention and treatment of non-alcoholic fatty liver disease (NAFLD) in mice. Methods C57BL/6 mice were fed with high-fat diet to establish NAFLD models. The experimental animals were divided into early prevention and later treatment groups. Both of these two experimental processes had five subgroups, including control, high-fat diet (HFD), low-dose vitamin C (LD-VC, 15 mg/kg per day), medium-dose vitamin C (MD-VC, 30 mg/kg per day) and high-dose vitamin C (HD-VC, 90 mg/kg per day) subgroup, with six mice in each subgroup. In the early prevention group, the mice were prophylactically received VC for 12 weeks. In the later treatment group, the mice were treated with different dose of VC for 12 weeks after fed with HFD for six weeks and confirmed NAFLD by liver pathology. The differences in body weight, perirenal adipose tissue mass and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triacylglycerol (TG) were observed among different groups. The scores of hepatocyte steatosis, lobular inflammation and ballooning in liver histopathology of mice in each group were evaluated by non-alcoholic fatty liver disease activity score (NAS) scoring system. Tukey′s multiple comparison test and Kruskal-Wallis H test were performed for statistical analysis. Results In the early prevention group, the body weight, perirenal adipose tissue mass, TG level and the score of liver steatosis of LD-VC subgroup were all lower than those of HFD subgroup ((30.27±0.94) g vs. (32.18±1.35) g, (0.25±0.05) g vs. (0.32±0.02) g, (0.25±0.02) mmol/L vs. (0.30±0.03) mmol/L, 0 vs. 1.0(1.0)). The body weight, perirenal adipose tissue mass, blood glucose level, TG level and score of liver steatosis of MD-VC subgroup were all lower than those of HFD subgroup ( (29.72±0.58) g vs. (32.18±1.35) g, (0.24±0.05) g vs. (0.32±0.02) g, (6.93±0.59) mmol/L vs. (8.33±1.02) mmol/L, (0.24±0.04) mmol/L vs. (0.30±0.03) mmol/L, 0 vs. 1.0(1.0)); meanwhile, the blood glucose level and TG level of HD-VC subgroup were both lower than those of HFD subgroup ((6.72±0.59) mmol/L vs. (8.33±1.02) mmol/L, (0.23±0.04) mmol/L vs. (0.30±0.03) mmol/L), and the differences were statistically significant (all P<0.05). In the later treatment group, TG level of LD-VC subgroup was lower than that of HFD subgroup ((0.25±0.07) mmol/L vs. (0.37±0.06) mmol/L); the body weight, perirenal adipose tissue mass, blood glucose level, TG level and liver steatosis score of MD-VC subgroup were lower than those of HFD subgroup ((29.93±1.28) g vs. (33.24±2.45) g, (0.29±0.08) g vs. (0.53±0.14) g, (7.63±0.57) mmol/L vs. (9.13±1.52) mmol/L, (0.23±0.03) mmol/L vs. (0.37±0.06) mmol/L, 0.5(1.0) vs. 2.0(1.0)); the blood glucose level and TG level of HD-VC subgroup were both lower than those of HFD subgroup ((7.20±0.72) mmol/L vs. (9.13±1.52) mmol/L, (0.19±0.03) mmol/L vs. (0.37±0.06) mmol/L); however the body weight, liver weight, perirenal adipose tissue mass and lobular inflammation score of HD-VC subgroup were all high than those of HFD subgroup( (36.34±2.44) g vs. (33.24±2.45) g, (1.18±0.07) g vs. (1.06±0.09) g, (0.78±0.17) g vs. (0.53±0.14) g, 1.0(1.0) vs.0(1.0)), and the differences were statistically significant (all P<0.05). The body weight, perirenal adipose tissue mass and the score of liver steatosis, lobular inflammation and ballooning of LD-VC subgroup of the early prevention group were all lower than those of LD-VC subgroup of the later treatment group ((30.27±0.94) g vs. (34.75±1.64) g, (0.25±0.05) g vs. (0.61±0.14) g, 0 vs.1.5(1.0), 0 vs. 0.5(1.0), 0 vs. 1.0(0)); and the body weight, liver weight, perirenal adipose tissue mass, ALT level, AST level and scores of liver steatosis and lobulor inflammation of HD-VC subgroup of the early prevention group were all lower than those of HD-VC subgroup of the late treatment group ((31.78±0.71) g vs. (36.34±2.44) g, (1.01±0.02) g vs. (1.18±0.07) g, (0.30±0.05) g vs. (0.78±0.17) g, (8.83±0.98) U/L vs. (12.75±2.05) U/L, (29.00±4.19) U/L vs. (41.88±14.36) U/L, 1.0(0) vs. 2.5(1.0), 0 vs. 1.0(1.0)), and the differences were statistically significant (all P<0.05). Conclusions MD-VC can prevent the occurrence of NAFLD in mice at an early stage, and it is also benefit to the later treatment of NAFLD in mice. However, HD-VC has potential risks in early prevention and later treatment of NAFLD in mice. Key words: Non-alcoholic fatty liver disease; Vitamin C; Prevention; Treatment; Mice

Fatty liver diseases, bile acids, and FXR

Nonalcoholic fatty liver disease (NAFLD) is leading chronic liver syndrome worldwide. Gut microbiota dysbiosis significantly contributes to the pathogenesis and severity of NAFLD. However, its role is complex and even unclear. Treatment of NAFLD through chemotherapeutic agents have been questioned because of their side effects on health. In this review, we highlighted and discussed the current understanding on the importance of gut microbiota, its dysbiosis and its effects on the gut-liver axis and gut mucosa. Further, we discussed key mechanisms involved in gut dysbiosis to provide an outline of its role in progression to NAFLD and liver cirrhosis. In addition, we also explored the potential role of probiotics as a treatment approach for the prevention and treatment of NAFLD. Based on the latest findings, it is evident that microbiota targeted interventions mostly the use of probiotics have shown promising effects and can possibly alleviate the gut microbiota dysbiosis, regulate the metabolic pathways which in turn inhibit the progression of NAFLD through the gut-liver axis. However, very limited studies in humans are available on this issue and suggest further research work to identify a specific core microbiome association with NAFLD and to discover its mechanism of pathogenesis, which will help to enhance the therapeutic potential of probiotics to NAFLD.