Metabolic disturbances in non-alcoholic fatty liver disease

2009 ◽  
Vol 116 (7) ◽  
pp. 539-564 ◽  
Author(s):  
Christopher D. Byrne ◽  
Rasaq Olufadi ◽  
Kimberley D. Bruce ◽  
Felino R. Cagampang ◽  
Mohamed H. Ahmed

NAFLD (non-alcoholic fatty liver disease) refers to a wide spectrum of liver damage, ranging from simple steatosis to NASH (non-alcoholic steatohepatitis), advanced fibrosis and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10 g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple non-invasive diagnostic tests to facilitate an estimate of prevalence. In certain subgroups of patients, such as those with Type 2 diabetes, the prevalence of NAFLD, defined by ultrasound, may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH and, in particular, to develop strategies for interventions to treat this condition. Currently, the ‘gold standard’ for the diagnosis of NASH is liver biopsy, and the need to undertake a biopsy has impeded research in subjects in this field. Limited results suggest that the prevalence of NASH could be as high as 11% in the general population, suggesting there is a worsening future public health problem in this field of medicine. With a burgeoning epidemic of diabetes in an aging population, it is likely that the prevalence of NASH will continue to increase over time as both factors are important risk factors for liver fibrosis. The purpose of this review is to: (i) briefly discuss the epidemiology of NAFLD to describe the magnitude of the future potential public health problem; and (ii) to discuss extra- and intra-hepatic mechanisms contributing to the pathogenesis of NAFLD, a better understanding of which may help in the development of novel treatments for this condition.

2021 ◽  
Author(s):  
Dandan Shan ◽  
Jinming Wang ◽  
Qiannan Di ◽  
Qianqian Jiang ◽  
Qian Xu

Non-alcoholic fatty liver disease (NAFLD) has increasingly become a serious public health problem. There is growing evidence that nonylphenol (NP) exposure may cause steatosis, but the underlying mechanism is not...


2010 ◽  
Vol 69 (2) ◽  
pp. 211-220 ◽  
Author(s):  
J. Bernadette Moore

Non-alcoholic fatty liver disease (NAFLD) is now the most common liver disease in both adults and children worldwide. As a disease spectrum, NAFLD may progress from simple steatosis to steatohepatitis, advanced fibrosis and cirrhosis. An estimated 20–35% of the general population has steatosis, 10% of whom will develop the more progressive non-alcoholic steatohepatitis associated with markedly increased risk of cardiovascular- and liver-related mortality. Development of NAFLD is strongly linked to components of the metabolic syndrome including obesity, insulin resistance, dyslipidaemia and type 2 diabetes. The recognition that NAFLD is an independent risk factor for CVD is a major public health concern. There is a great need for a sensitive non-invasive test for the early detection and assessment of the stage of NAFLD that could also be used to monitor response to treatment. The cellular and molecular aetiology of NAFLD is multi-factorial; genetic polymorphisms influencing NAFLD have been identified and nutrition is a modifiable environmental factor influencing NAFLD progression. Weight loss through diet and exercise is the primary recommendation in the clinical management of NAFLD. The application of systems biology to the identification of NAFLD biomarkers and factors involved in NAFLD progression is an area of promising research.


Author(s):  
Claudio Tana ◽  
Stefano Ballestri ◽  
Fabrizio Ricci ◽  
Angelo Di Vincenzo ◽  
Andrea Ticinesi ◽  
...  

New evidence suggests that non-alcoholic fatty liver disease (NAFLD) has a strong multifaceted relationship with diabetes and metabolic syndrome, and is associated with increased risk of cardiovascular events, regardless of traditional risk factors, such as hypertension, diabetes, dyslipidemia, and obesity. Given the pandemic-level rise of NAFLD—in parallel with the increasing prevalence of obesity and other components of the metabolic syndrome—and its association with poor cardiovascular outcomes, the question of how to manage NAFLD properly, in order to reduce the burden of associated incident cardiovascular events, is both timely and highly relevant. This review aims to summarize the current knowledge of the association between NAFLD and cardiovascular disease, and also to discuss possible clinical strategies for cardiovascular risk assessment, as well as the spectrum of available therapeutic strategies for the prevention and treatment of NAFLD and its downstream events.


2019 ◽  
Vol 16 (1) ◽  
pp. 39-45
Author(s):  
Cemal Kemaloglu ◽  
Melek Didem Kemaloglu

Objective: The aim of this study is to identify the relationship between carotid intima-media thickness (c-imt) and non-alcoholic fatty liver disease (NAFLD), and to determine whether NAFLD is an independent predictor for the progression of atherosclerosis.  Method: This is a prospective randomized controlled study. 103 NAFLD patients who have hepatosteatosis with grade II and above were enrolled in this study. Patients were divided into NAFLD with metabolic syndrome (MS) and NAFLD without MS groups and compared with 50 healthy people. Basal demographic characteristics and C-imt of all patients and control group were measured.  Results: C-imt and carotid cross sectional area rates in the NAFLD groups were significantly higher than those in the control group. The mean and max. c-imt levels were significantly higher in the NAFLD group with metabolic syndrome (p<0,001). Homeostatic Model of Assessment-Insulin Resistance (HOMA-IR) levels were increased in the group with metabolic syndrome than those in the group without metabolic syndrome, with statistical significance (p<0.001). There was no difference in c-imt levels between HOMA-IR positive and negative groups (p=0.254) in patients with NAFLD and without metabolic syndrome. There was only a mild positive corelation between c-imt levels and high sensitive C-Reactive protein (hs-CRP) levels in metabolic syndrome positive group (p=0.026 r=0.30).  Conclusion: NAFLD was a significant predictor to determine the increased risk of carotid atherosclerosis. 


2019 ◽  
Vol 20 (9) ◽  
pp. 2215 ◽  
Author(s):  
Hamza El Hadi ◽  
Angelo Di Vincenzo ◽  
Roberto Vettor ◽  
Marco Rossato

With the progressive epidemics of obesity, non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in adults and children. The increasing prevalence and incidence of NAFLD with advanced fibrosis is concerning because patients appear to experience higher non-liver-related morbidity and mortality than the general population. Recent clinical evidence suggests that NAFLD is directly associated with an increased risk of cardio-metabolic disorders. This mini review describes briefly the current understanding of the pathogenesis of NAFLD, summarizing the link between NAFLD and cardio-metabolic complications, focusing mainly upon ischemic stroke, type 2 diabetes mellitus (DM), hypertension, chronic kidney disease (CKD) and cardiac arrhythmias. In addition, it describes briefly the current understanding of the pathogenesis of NAFLD.


2019 ◽  
Vol 78 (3) ◽  
pp. 290-304 ◽  
Author(s):  
J. Bernadette Moore

Non-alcoholic fatty liver disease (NAFLD) is now a major public health concern with an estimated prevalence of 25–30% of adults in many countries. Strongly associated with obesity and the metabolic syndrome, the pathogenesis of NAFLD is dependent on complex interactions between genetic and environmental factors that are not completely understood. Weight loss through diet and lifestyle modification underpins clinical management; however, the roles of individual dietary nutrients (e.g. saturated and n-3 fatty acids; fructose, vitamin D, vitamin E) in the pathogenesis or treatment of NAFLD are only partially understood. Systems biology offers valuable interdisciplinary methods that are arguably ideal for application to the studying of chronic diseases such as NAFLD, and the roles of nutrition and diet in their molecular pathogenesis. Although present in silico models are incomplete, computational tools are rapidly evolving and human metabolism can now be simulated at the genome scale. This paper will review NAFLD and its pathogenesis, including the roles of genetics and nutrition in the development and progression of disease. In addition, the paper introduces the concept of systems biology and reviews recent work utilising genome-scale metabolic networks and developing multi-scale models of liver metabolism relevant to NAFLD. A future is envisioned where individual genetic, proteomic and metabolomic information can be integrated computationally with clinical data, yielding mechanistic insight into the pathogenesis of chronic diseases such as NAFLD, and informing personalised nutrition and stratified medicine approaches for improving prognosis.


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