The EMRG Consortium: a gate to identify the burden of metabolic (dysfunction)-associated fatty liver disease in Egypt (original) (raw)
Related papers
2021
Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized public health problem worldwide. To emphasize the close pathophysiological links between NAFLD and overweight/obesity, insulin resistance, and related metabolic comorbidities, a consensus statement of international experts in 2020 has recommended to replace the old acronym NAFLD with “metabolic dysfunction-associated fatty liver disease” (MAFLD). A set of “positive” criteria to diagnose MAFLD, regardless of daily alcohol consumption, has also been proposed. A “positive” definition of MAFLD and its special focus on the metabolic causative drivers of this liver disease is expected to reduce patient confusion on disease etiology, which can, in turn, improve the identification and awareness of this common and burdensome liver disease among both primary care physicians and specialists. However, the proposal to change the terminology from NAFLD to MAFLD is still under intense discussion, as also recently highlighted by a panel of international experts (led by Dr. Polyzos and Mantzoros), which is the main topic of discussion of this commentary. Further studies are required to better understand whether, and how, the proposed changes to the diagnostic criteria for MAFLD may impact on the risk of adverse hepatic and extra-hepatic clinical outcomes.
Perspectives of nonalcoholic fatty liver disease research: a personal point of view
2020
Rational government of patient fluxes from primary care to hepatology clinic is a priority of nonalcoholic fatty liver disease (NAFLD) research. Estimating pre-test probability of disease, risk of fibrosis progression, and exclusion of competing causes of liver disease must be addressed. Here we propose a novel taxonomic classification of NAFLD based on hepatic, pathogenic and systemic features of disease in the individual patient. The variable course of disease in any given patient remains a clinical enigma. Therefore, future studies will have to better characterize the role of genetic polymorphisms, family and personal history, diet, alcohol, physical activity and drugs as modifiers of the course of disease and clues to the early diagnosis of hepatocellular carcinoma. A better understanding of these, together with a taxonomic diagnosis, may prompt a more accurate personalization of care. For example, understanding the putative role of psycho-depression in NAFLD promises to revolutionize disease management in a proportion of cases. Similarly, sex differences in outcome and response to treatment are insufficiently characterized. More studies are awaited regarding those forms of NAFLD which occur secondary to endocrine derangements. The intersections between NAFLD and the lung must better be defined. These include the bi-directional associations of NAFLD and chronic obstructive pulmonary disease and sleep apnoea syndrome, as well as the totally unexplored chapter of NAFLD and coronavirus disease 2019 (COVID-19). Finally, the therapeutic roles of intermittent fasting and anticoagulation must be assessed. In conclusion, over the last 20 years, NAFLD has taught us a lot regarding the pathogenic importance of insulin resistance, the limitations of correcting this in the treatment of NAFLD, the root causes of diabetes and the metabolic syndrome, sex differences in disease and the role of nuclear receptors. However, the overwhelming COVID-19 pandemic is now expected to reset the priorities of public health.
Nonalcoholic Fatty Liver Disease (NAFLD) Name Change: Requiem or Reveille?
2021
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 ...
Journal of Hepatology, 2021
cell death in AML-12 hepatocytes. Details surrounding cellular/ molecular mechanisms are still under investigation. Unlike ALD with a known etiology, the etiology for non-alcoholic fatty liver disease (NAFLD) is very heterogeneous. Acyl-CoA oxidase 2 (Acox2) encodes a branched-chain acyl-CoA oxidase, a peroxisomal enzyme involved in the metabolism of branched-chain fatty acids and bile acid intermediates. 5 Homozygous Acox2 knockout (Acox2-/-) mice in a C57BL/6N background spontaneously developed clinical symptoms of NAFLD including steatosis, inflammation, and fibrosis at the age of 4 months. Combined with proteomic and metabolomic analysis, Zhang and colleagues discovered that Acox2-/mice showed significantly reduced 1-MNA levels in both the blood and liver in comparison to wild-type mice. Given the critical role of NNMT in regulating both SAM-and NAD +-dependent metabolism, the findings by Zhang and colleagues are exciting and of great interest. However, much research is needed to determine if 1-MNA reduction is derived from NNMT downregulation or an overactivation of its degradation, and furthermore if 1-MNA reduction is a cause for NAFLD development and progression in Acox2-/mice or simply a consequence of Acox2 absence, accumulation of C27 intermediate metabolites, and failure of C24 bile acid synthesis in these mice. NNMT upregulation in obesity and metabolic syndrome has been reported and NNMT knockdown alleviates obesity-related hepatic steatosis. 6,7 Clinically, NAFLD development and progression are closely associated with excess energy intake, increased visceral fat accumulation, and insulin resistance. 8 However, none of these features manifest in Acox2-/mice. Therefore, it is difficult to conclude that the depletion of NNMT and that of 1methylnicotinamide are risk factors for NAFLD development. We agree that NNMT downregulation may contribute to NAFLD progression to late-stage phenotypes, including hepatocellular carcinoma. Using liver samples from patients with severe alcoholic hepatitis, we observed a significant reduction of NNMT expression, at both mRNA and protein levels. Moreover, consistent with several previous reports, 9,10 we have unpublished data confirming that, unlike many other types of human cancers, NNMT expression is dramatically downregulated in human hepatocellular carcinoma samples. What causes this change in expression, and whether this change promotes NAFLD progression and carcinogenesis remain open questions.
Redefining fatty liver disease: an international patient perspective
The Lancet Gastroenterology & Hepatology
Despite its increased recognition as a major health threat, fatty liver disease associated with metabolic dysfunction remains largely underdiagnosed and undertreated. An international consensus panel has called for the disease to be renamed from non-alcoholic fatty liver disease (NAFLD) to metabolic-associated fatty liver disease (MAFLD) and has suggested how the disease should be diagnosed. This Viewpoint explores the call from the perspective of patient advocacy groups. Patients are well aware of the negative consequences of the NAFLD acronym. This advocacy group enthusiastically endorses the call to reframe the disease, which we believe will ultimately have a positive effect on patient care and quality of life and, through this effect, will reduce the burden on health-care systems. For patients, policy makers, health planners, donors, and non-hepatologists, the new acronym MAFLD is clear, squarely placing the disease as a manifestation of metabolic dysfunction and improving understanding at a public health and patient level. The authors from representative patient groups are supportive of this change, particularly as the new acronym is meaningful to all citizens as well as governments and policy makers, and, above all, is devoid of any stigma.
Aisf Position Paper on Nonalcoholic Fatty Liver Disease (Nafld): Updates and Future Directions
Digestive and Liver Disease, 2017
This review summarizes our current understanding of nonalcoholic fatty liver disease (NAFLD), a multifactorial systemic disease resulting from a complex interaction between a specific genetic background and multiple environmental/metabolic "hits". The role of gut microbiota, lipotoxicity, inflammation and their molecular pathways is reviewed indepth. We also discuss the epidemiology and natural history of NAFLD by pinpointing the remarkably high prevalence of NAFLD worldwide and its inherent systemic complications: hepatic (steatohepatitis, advanced fibrosis and cirrhosis), cardio-metabolic (cardiovascular disease, cardiomyopathy, arrhythmias and type 2 diabetes) and neoplastic (primary liver cancers and extra-hepatic cancers). Moreover, we critically report on the diagnostic role of non-invasive biomarkers, imaging techniques and liver biopsy, which remains the reference standard for diagnosing the disease, but cannot be proposed to all patients with suspected NAFLD. Finally, the management of NAFLD is also reviewed, by highlighting the lifestyle changes and the pharmacological options, with a focus on the innovative drugs. We conclude that the results of ongoing studies are eagerly expected to lead to introduce into the clinical arena new diagnostic and prognostic biomarkers, prevention and surveillance strategies as well as to new drugs for a tailored approach to the management of NAFLD in the individual patient.
The OMICs Window into Nonalcoholic Fatty Liver Disease (NAFLD)
Metabolites, 2019
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.
With the increasing prevalence of obesity and type 2 diabetes, fatty liver disease associated with metabolic dysfunction is a global health problem, especially because it is one of the earliest consequences of obesity and it precedes diabetes development. Fatty liver disease associated with metabolic dysfunction is of particular concern in the Middle East and north Africa, where its prevalence is greater than that in the rest of the world. Despite the magnitude of the problem, no regional guidelines have been developed to address this disease. This Review describes suggestions of redefining fatty liver disease associated with metabolic dysfunction, including its terminology and criteria for diagnosis. Experts have raised serious concerns on the current nomenclature, which labels the disease as non-alcoholic fatty liver disease (NAFLD), and its diagnostic criteria. The panel reached a consensus that the disease should be renamed as metabolicassociated fatty liver disease (MAFLD) and that the disease should be diagnosed by positive criteria. The aim is now to work with authorities across the region to implement these proposed changes and reflect them in health-care policy and to improve health care for patients in this region.
What’s Past Is Prologue: History of Nonalcoholic Fatty Liver Disease
Metabolites, 2020
Since the initial descriptions in the early 1980s by Dr. Ludwig et al. and Drs. Schaffner and Thaler, who firstly coined the terms nonalcoholic steatohepatitis (NASH) and nonalcoholic fatty liver disease (NAFLD), this liver disease has become a global health problem worldwide, causing considerable liver-related and extra-hepatic morbidity and mortality. Based on pathophysiological insights gained from the past decades, it has been clearly established that NAFLD is a metabolic liver disease whose etiology and pathogenesis extends beyond the liver and that NAFLD has important clinical implications, especially in terms of an increased risk of developing both cardiovascular disease (which represents the leading cause of death in this patient population) and other extra-hepatic manifestations, such as type 2 diabetes mellitus, chronic kidney disease, and some extra-hepatic cancers. The aim of this brief commentary is to discuss a recent review article written by Dr. Lonardo and colleague...