Nonalcoholic Fatty Liver Disease (NAFLD): Pathogenesis and Noninvasive Diagnosis.
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ABSTRACT:
SUBMITTER: Dorairaj V
PROVIDER: S-EPMC8773432 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) comprises hepatic alterations with increased lipid accumulation (steatosis) without or with inflammation (nonalcoholic steatohepatitis, NASH) and/or fibrosis in the absence of other causes of liver disease. NAFLD is developing as a burgeoning health challenge, mainly due to the worldwide obesity and diabetes epidemics.Scope of reviewThis review summarizes the knowledge on the pathogenesis underlying NAFLD by focusing on studies in humans and on hypercaloric nutrition, including effects of saturated fat and fructose, as well as adipose tissue dysfunction, leading to hepatic lipotoxicity, abnormal mitochondrial function, and oxidative stress, and highlights intestinal dysbiosis. These mechanisms are discussed in the context of current treatments targeting metabolic pathways and the results of related clinical trials.Major conclusionsRecent studies have provided evidence that certain conditions, for example, the severe insulin-resistant diabetes (SIRD) subgroup (cluster) and the presence of an increasing number of gene variants, seem to predispose for excessive risk of NAFLD and its accelerated progression. Recent clinical trials have been frequently unsuccessful in halting or preventing NAFLD progression, perhaps partly due to including unselected cohorts in later stages of NAFLD. On the basis of this literature review, this study proposed screening in individuals with the highest genetic or acquired risk of disease progression, for example, the SIRD subgroup, and developing treatment concepts targeting the earliest pathophysiolgical alterations, namely, adipocyte dysfunction and insulin resistance.
| S-EPMC8324683 | biostudies-literature
Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and is the most common liver disease in the developed world. In children with suspected NAFLD, present guidelines suggest consideration of alternative diagnoses via extensive blood testing, though the yield of this work up is unknown. Furthermore, the gold standard diagnostic test for NAFLD remains liver biopsy, making the development of non-invasive tests critically important.ObjectivesOur objectives are: 1) to determine the accuracy of elastography and multiple serum biomarkers - each assessed individually and as algorithms (including those previously tested in adults) - for the diagnosis of nonalcoholic steatohepatitis (NASH) and early fibrosis in children and (2) to examine the utility of extensive testing for rare alternative diagnoses in overweight or obese children with elevated alanine aminotransferase (ALT) suspected to have NAFLD.DesignThis is an ongoing, cross-sectional study in children 2-18 years of age with up to 2 years of prospective follow up. Eligible patients are asymptomatic, overweight or obese, and have an ALT ≥35 U/L upon enrollment. Two forms of elastography are obtained serially along with anthropometric data and routine laboratory tests. Elastography and serum biomarkers are also performed immediately prior to any clinically-indicated biopsy.MethodsBetween April 2015 and April 2018, 193 children have been enrolled in this ongoing study and 71 have undergone liver biopsy. Here we carefully report the rationale, methodology, and preliminary data for this study.
| S-EPMC6249118 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver diseases and can progress to advanced fibrosis and end-stage liver disease. Thus, intensive research has been performed to develop noninvasive methods for the diagnosis of nonalcoholic steatohepatitis (NASH) and fibrosis. Currently, no single noninvasive tool covers all of the stages of pathologies and conditions of NAFLD, and the cost and feasibility of known techniques are also important issues. Blood biomarkers for NAFLD may be useful to select subjects who need ultrasonography (US) screening for NAFLD, and noninvasive tools for assessing fibrosis may be helpful to exclude the probability of significant fibrosis and to predict advanced fibrosis, thus guiding the decision of whether to perform liver biopsy in patients with NAFLD. Among various methods, magnetic resonance-based methods have been shown to perform better than other methods in assessing steatosis as well as in detecting hepatic fibrosis. Many genetic markers are associated with the development and progression of NAFLD. Further well-designed studies are needed to determine which biomarker panels, imaging studies, genetic marker panels, or combinations thereof perform well for diagnosing NAFLD, differentiating NASH and fibrosis, and following-up NAFLD, respectively.
| S-EPMC7386127 | biostudies-literature
Project description:The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing recently and has become one of the most common clinical liver diseases. Since the pathogenesis of NAFLD has not been completely elucidated, few effective therapeutic drugs are available. As the "second genome" of human body, gut microbiota plays an important role in the digestion, absorption and metabolism of food and drugs. Gut microbiota can act as an important driver to advance the occurrence and development of NAFLD, and to accelerate its progression to cirrhosis and hepatocellular carcinoma. Growing evidence has demonstrated that gut microbiota and its metabolites directly affect intestinal morphology and immune response, resulting in the abnormal activation of inflammation and intestinal endotoxemia; gut dysbiosis also causes dysfunction of gut-liver axis via alteration of bile acid metabolism pathway. Because of its composition diversity and disease-specific expression characteristics, gut microbiota holds strong promise as novel biomarkers and therapeutic targets for NAFLD. Intervening intestinal microbiota, such as antibiotic/probiotic treatment and fecal transplantation, has been a novel strategy for preventing and treating NAFLD. In this article, we have reviewed the emerging functions and association of gut bacterial components in different stages of NAFLD progression and discussed its potential implications in NAFLD diagnosis and therapy.
| S-EPMC9679376 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic abnormalities worldwide. Nonalcoholic steatohepatitis (NASH) is part of the spectrum of NAFLD and leads to progressive liver disease, such as cirrhosis and hepatocellular carcinoma. In NASH patient, fibrosis represents the major predictor of liver-related mortality; therefore, it is important to have an early and accurate diagnosis of NASH. The current gold standard for the diagnosis of NASH is still liver biopsy. The development of biomarkers able to predict disease severity, prognosis, as well as response to therapy without the need for a biopsy is the focus of most up-to-date genomic, transcriptomic, proteomic, and metabolomic research. In the future, patients might be diagnosed and treated according to their molecular signatures. In this short review, we discuss how information from genomics, proteomics, and metabolomics contribute to the understanding of NAFLD pathogenesis.
| S-EPMC6409793 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is on the rise and has become a major etiology for chronic liver disease. It is frequently associated with obesity, insulin resistance, hypertension, and dyslipidemia and is considered the hepatic manifestation of metabolic syndrome. In this review, we present a summary of the epidemiology and pathogenesis of NAFLD, and discuss the clinical evaluation and stratification of NAFLD patients into low, intermediate, and high risk with respect to liver-related outcomes. While diet and exercise are the cornerstone of treatment in all patients, the low rate of adherence and inadequacy of these recommendations necessitate pharmacologic intervention, especially in intermediate- and high-risk patients. We discuss vitamin E and pioglitazone which are often used as first-line therapy by many practitioners, with pentoxifylline and liraglutide as backup agents. Several drugs are in advanced-phase clinical trials and will likely change the landscape for management of NAFLD in the very near future.
| S-EPMC5491796 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is estimated to afflict approximately 1 billion individuals worldwide. In a subset of NAFLD patients, who have the progressive form of NAFLD termed nonalcoholic steatohepatitis (NASH), it can progress to advanced fibrosis, cirrhosis, hepatocellular carcinoma, and liver-related morbidity and mortality. NASH is typically characterized by a specific pattern on liver histology, including steatosis, lobular inflammation, and ballooning with or without peri-sinusoidal fibrosis. Thus, key issues in NAFLD patients are the differentiation of NASH from simple steatosis and identification of advanced hepatic fibrosis. Until now, liver biopsy has been the gold standard for identifying these 2 critical end points, but has well-known limitations, including invasiveness; rare but potentially life-threatening complications; poor acceptability; sampling variability; and cost. Furthermore, due to the epidemic proportion of individuals with NAFLD worldwide, liver biopsy evaluation is impractical, and noninvasive assessment for the diagnosis of NASH and fibrosis is needed. Although much of the work remains to be done in establishing cost-effective strategies for screening for NASH, advanced fibrosis, and cirrhosis, in this review, we summarize the current state of the noninvasive assessment of liver disease in NAFLD, and we provide an expert synthesis of how these noninvasive tools could be utilized in clinical practice. Finally, we also list the key areas of research priorities in this area to move forward clinical practice.
| S-EPMC7505052 | biostudies-literature
Project description:Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual's susceptibility to NAFLD. Modifications of the histones amino-terminal ends are key factors in the maintenance of chromatin structure and gene expression (cAMP-responsive element binding protein H (CREBH) or SIRT1). Activation of SIRT1 showed potential against the physiological mechanisms related to NAFLD. Abnormal DNA methylation represents a starting point for cancer development in NAFLD patients. Besides, the evaluation of circulating miRNA profiles represents a promising approach to assess and non-invasively monitor liver disease severity. To date, there is no approved pharmacologic therapy for NAFLD and the current treatment remains weight loss with lifestyle modification and exercise. In this review, the status of research into relevant genetic and epigenetic modifiers of NAFLD progression will be discussed.
| S-EPMC5877772 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) affects about a quarter of the world's population and poses a major health and economic burden globally. Recently, there have been hasty attempts to rename NAFLD to metabolic-associated fatty liver disease (MAFLD) despite the fact that there is no scientific rationale for this. Quest for a "positive criterion" to diagnose the disease and destigmatizing the disease have been the main reasons put forth for the name change. A close scrutiny of the pathogenesis of NAFLD would make it clear that NAFLD is a heterogeneous disorder, involving different pathogenic mechanisms of which metabolic dysfunction-driven hepatic steatosis is only one. Replacing NAFLD with MAFLD would neither enhance the legitimacy of clinical practice and clinical trials, nor improve clinical care or move NAFLD research forward. Rather than changing the nomenclature without a strong scientific backing to support such a change, efforts should be directed at understanding NAFLD pathogenesis across diverse populations and ethnicities which could potentially help develop newer therapeutic options.
| S-EPMC8666378 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is a multifactorial metabolic disorder that was first described in 1980. It has been prevalent and on the rise for many years and is associated with other metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). NAFLD can be best described as a metabolic dysfunction that stems from insulin resistance-induced hepatic lipogenesis. This lipogenesis increases oxidative stress and hepatic inflammation and is often potentiated by genetic and gut microbiome dysfunction. As NAFLD progresses from simple steatosis to non-alcoholic steatohepatitis (NASH) and to cirrhosis and hepatocellular carcinoma (HCC), the odds of complications including cardiovascular disease (CVD), chronic kidney disease (CKD), and overall mortality increase. The aim of this review is to describe the metabolic causes and consequences of NAFLD while examining the risks that each stage of NAFLD poses. In this review, the etiology of "lean" NAFLD, the impact of obesity, T2DM, genetics, and microbiome dysbiosis on NAFLD progression are all explored. This review will also discuss the core issue behind the progression of NAFLD: insulin resistance (IR). Upon describing the causes and consequences of NAFLD, the effectiveness of diet modification, lifestyle changes, and glucagon-like peptide 1 receptor (GLP-1) agonists to retard NAFLD progression and stem the rate of complications is examined.
| S-EPMC8626571 | biostudies-literature