NASH / NAFLD

Non-alcoholic fatty liver disease (NAFLD) is a growing health problem due to the increased obesity rates, among other factors. In its more severe stage (NASH), inflammation, hepatocellular ballooning and fibrosis are present in the liver, which can further evolve to total liver dysfunction or even hepatocarcinoma. As a metabolic disease, is associated to environmental factors such as diet and lifestyle conditions, which in turn can influence the epigenetic landscape of the cells, affecting to the gene expression profile and chromatin organization...

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails...

BACKGROUND AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is characterized by ectopic deposition of fat in the liver, in the absence of other secondary causes of fat buildup. The relationship between NAFLD, including alanine aminotransferase (ALT), and glycated haemoglobin (HbA1c), is important for predicting the severity of disease and prognosis. This study aims to investigate the association of HbA1c in type 2 diabetes mellitus (T2DM) patients with NAFLD via measuring the ALT levels...

The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50  = 4...

Nonalcoholic fatty liver disease (NAFLD) is a common liver disorder affecting a quarter of the global residents. Progression of NAFL into nonalcoholic steatohepatitis (NASH) may cause cirrhosis, liver cancer, and failure. Gut microbiota imbalance causes microbial components translocation into the circulation, triggering liver inflammation and NASH-related fibrosis. MicroRNAs (miRNAs) regulate gene expression via repressing target genes. Exosomal miRNAs are diagnostic and prognostic biomarkers for NAFL and NASH liver damage...

A family of Peptidyl-prolyl isomerases (PPIases), called Cyclophilins, localize to numerous intracellular and extracellular locations where they contribute to a variety of essential functions. We previously reported that non-immunosuppressive pan-cyclophilin inhibitor drugs like reconfilstat (CRV431) or NV556 decreased multiple aspects of non-alcoholic fatty liver disease (NAFLD) in mice under two different non-alcoholic steatohepatitis (NASH) mouse models. Both CRV431 and NV556 inhibit several cyclophilin isoforms, among which cyclophilin D (CypD) has not been previously investigated in this context...

Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition observed globally, with the potential to progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and even hepatocellular carcinoma. Currently, the US Food and Drug Administration (FDA) has not approved any drugs for the treatment of NAFLD. NAFLD is characterized by histopathological abnormalities in the liver, such as lipid accumulation, steatosis, hepatic balloon degeneration, and inflammation. Dysbiosis of the gut microbiota and its metabolites significantly contribute to the initiation and advancement of NAFLD...

There is increasing appreciation of the complex interaction between nonalcoholic fatty liver disease (NAFLD) with type 2 diabetes (T2D) and insulin resistance. Not only is the prevalence of NAFLD disease high among patients with T2D, the liver disease is also more progressive. Currently, the global prevalence of NAFLD in the general population (2016-2019) is 38 %. The prevalence of T2D among those with NAFLD is approximately 23 % while the prevalence of NAFLD among those with T2D can be as high as 70 %...

Circulating lactate is a fuel source for liver metabolism but may exacerbate metabolic diseases such as nonalcoholic steatohepatitis (NASH). Indeed, haploinsufficiency of lactate transporter monocarboxylate transporter 1 (MCT1) in mice reportedly promotes resistance to hepatic steatosis and inflammation. Here, we used adeno-associated virus (AAV) vectors to deliver thyroxin binding globulin (TBG)-Cre or lecithin-retinol acyltransferase (Lrat)-Cre to MCT1fl/fl mice on a choline-deficient, high-fat NASH diet to deplete hepatocyte or stellate cell MCT1, respectively...

BACKGROUND: Based on the rapidly growing global burden of non-alcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH), in order to evaluate the efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of NAFLD or NASH this paper presents a systematic review and meta-analysis of randomized controlled trials(RCTs). METHODS: In this systematic review and meta-analysis, We searched PubMed, Medline, Web of Science and The Cochrane Library databases...

Identifying effective, feasible, low-cost interventions that promote sustainable lifestyle changes in nonalcoholic fatty liver disease (NAFLD) is a key unmet need. The aim of this study was to assess predictors of lifestyle practice patterns of NAFLD patients and evaluate the implementation of a mobile technology-based intervention. We prospectively enrolled adults with NAFLD (diagnosed by imaging or biopsy). Individuals with additional liver diseases or decompensated cirrhosis were excluded. Patient were randomized to usual care or a FitBit based program for 6-months...

BACKGROUND: Non-invasive scores have been proposed to identify patients with fibrotic, metabolic dysfunction associated steatohepatitis (MASH), who are at the highest risk of progression to complications of cirrhosis and may benefit from pharmacologic treatments. However, data in type 2 diabetes (T2DM) patients are lacking. The aim of this multicenter prospective study was to compare head-to-head FAST (FibroScan-aspartate aminotransferase [AST]), MAST (magnetic resonance imaging [MRI]-AST), MEFIB (magnetic resonance elastography [MRE] plus FIB-4), and FNI (fibrotic NASH index) for detecting fibrotic MASH in T2DM patients...

BACKGROUND: Fatty liver disease (FLD) poses a significant global health concern worldwide, with its classification into nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (AFLD) contingent upon the presence or absence of chronic and excessive alcohol consumption. The absence of specific therapeutic interventions tailored to FLD at various stages of the disease renders its treatment exceptionally arduous. Despite the fact that FLD and hyperlipidemia are intimately associated, there is still debate over how lipid-lowering medications affect FLD...

PURPOSE: Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), which has a high risk of cirrhosis, liver failure, and hepatocellular carcinoma. Piperine (Pip) is an extract of plants with powerful anti-inflammatory effects, however, the function of Pip in NASH remains elusive. Here, we aim to explore the role of Pip in NASH and to find the possible mechanisms. METHODS: Methionine and choline-deficient (MCD) diets were used to induce steatohepatitis, methionine- and choline-sufficient (MCS) diets were used as the control...

The onset of metabolic dysfunction-associated steatohepatitis (MASH) or non-alcoholic steatohepatitis (NASH) represents a tipping point leading to liver injury and subsequent hepatic complications in the natural progression of what is now termed metabolic dysfunction-associated steatotic liver diseases (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD). With no pharmacological treatment currently available for MASH/NASH, the race is on to develop drugs targeting multiple facets of hepatic metabolism, inflammation, and pro-fibrotic events, which are major drivers of MASH...

Nonalcoholic fatty liver disease (NAFLD) exponentially affects the global healthcare burden, and it is currently gaining increasing interest in relation to its potential impact on central nervous system (CNS) diseases, especially concerning cognitive deterioration and dementias. Overall, scientific research nowadays extends to different levels, exploring NAFLD's putative proinflammatory mechanism of such dysmetabolic conditions, spreading out from the liver to a multisystemic involvement. The aim of this review is to analyze the most recent scientific literature on cognitive involvement in NAFLD, as well as understand its underlying potential background processes, i...

Background and Objectives : Non-alcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. It progresses from simple steatosis to non-alcoholic steatohepatitis (NASH). Fibrosis is often present during NAFLD progression; however, factors determining which subjects develop NASH or fibrosis are unclear. Insulin-like growth factor binding proteins (IGFBPs) are a family of secreted proteins involved in senescence and scarring, mainly synthetized in the liver. Here, we aimed to study the association of IGFBPs and their induced senescence with the progression of NAFLD and liver fibrosis...

Non-alcoholic steatohepatitis (NASH, also known as MASH) is a severe form of non-alcoholic fatty liver disease (NAFLD, also known as MASLD). Emerging data indicate that the progression of the disease to MASH is higher in postmenopausal women and that genetic susceptibility increases the risk of MASH-related cirrhosis. This study aimed to investigate the association between genetic polymorphisms in MASH and sexual dimorphism. We applied whole-exome sequencing (WES) to identify gene variants in 8 age-adjusted matched pairs of livers from both male and female patients...

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are closely related liver conditions that have become more prevalent globally. This review examines the intricate interplay between microbiome dysbiosis and mitochondrial dysfunction in the development of NAFLD and NASH. The combination of these two factors creates a synergistic situation referred to as "double trouble", which promotes the accumulation of lipids in the liver and the subsequent progression from simple steatosis (NAFLD) to inflammation (NASH)...

Hepatobiliary diseases have a high prevalence worldwide, with a wide range of diseases involved in the liver and biliary system. Modifications in gut microbiota have been proven to have an association with unbalanced intestinal homeostasis and the dysfunction of host metabolism and the immune system, which can be the risk factors for many hepatobiliary diseases, such as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), nonalcoholic fatty steatohepatitis (NASH), hepatitis, cirrhosis, hepatocellular carcinoma (HCC) and cholestasis, as well as infection due to liver transplantation...