Effect of cofactors on NAFLD/NASH and MAFLD. A paradigm illustrating the pathomechanics of organ dysfunction

Lonardo, Amedeo; Singal, Ashwani K.; Osna, Natalia A.; Kharbanda, Kusum K.

doi:10.20517/mtod.2022.14

Cited by 34 publications

(28 citation statements)

References 131 publications

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“…Following the current directions, there is a need for adopting a better term for liver steatosis to emphasize what the disease "is", rather than what "it is not" when considering the burden of contributing metabolic abnormalities, pathophysiological mechanisms, diagnostic, and therapeutic strategies [84]. Since 2020 experts from 134 countries have proposed the transition of terminology from NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) [10] which points to the close association between fatty liver, metabolic disorders and target organ dysfunction (i.e., diabetes, chronic kidney disease, atherosclerosis, lung dysfunction, colon cancer, and both intrahepatic and extrahepatic events) [86], rather than on exclusion criteria [12]. The new terminology is not yet endorsed by international societies, including European Association for the Study of Liver Disease (EASL) and the American Association for the Study of Liver Disease AASLD) [87].…”

Section: Mafld: Debate About Nomenclaturementioning

confidence: 99%

“…3) [84]. The discussion has gone further with a novel taxonomic classification of NAFLD based on hepatic, pathogenic and systemic features of disease in the individual patient [86,128]. The liver-determinant-extrahepatic (LDE) system applies to NAFLD and MAFLD and combines information on liver status independently of histology (L), determinants which include sex and reproductive status, genetic, and endocrine assessment (D), and extrahepatic manifestations at a metabolic, cardiovascular, and tumor level (E).…”

Section: Fatty Liver Disease: More Acronyms On the Waymentioning

confidence: 99%

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NAFLD, MAFLD, and beyond: one or several acronyms for better comprehension and patient care

Portincasa

2023

Intern Emerg Med

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The term non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common type of chronic liver disease. NAFLD points to excessive hepatic fat storage and no evidence of secondary hepatic fat accumulation in patients with “no or little alcohol consumption”. Both the etiology and pathogenesis of NAFLD are largely unknown, and a definitive therapy is lacking. Since NAFLD is very often and closely associated with metabolic dysfunctions, a consensus process is ongoing to shift the acronym NAFLD to MAFLD, i.e., metabolic-associated fatty liver disease. The change in terminology is likely to improve the classification of affected individuals, the disease awareness, the comprehension of the terminology and pathophysiological aspects involved, and the choice of more personalized therapeutic approaches while avoiding the intrinsic stigmatization due to the term “non-alcoholic”. Even more recently, other sub-classifications have been proposed to concentrate the heterogeneous causes of fatty liver disease under one umbrella. While awaiting additional validation studies in this field, we discuss the main reasons underlying this important shift of paradigm.

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Section: Mafld: Debate About Nomenclaturementioning

confidence: 99%

Section: Fatty Liver Disease: More Acronyms On the Waymentioning

confidence: 99%

NAFLD, MAFLD, and beyond: one or several acronyms for better comprehension and patient care

Portincasa

2023

Intern Emerg Med

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“…Supplementary disease cofactors [33] and particularly lifestyle habits may also participate in fine-tuning the odds of extra-hepatic cancers among those with MFLS. These risk modifiers include epigenetics, alcohol consumption, eating habits (scarcity of fiber and an excess of saturated fats), and sedentary behavior which closely interact with viral infections, drugs, and immunological factors in predisposing to/protecting from extra-hepatic cancers.…”

Section: Abbreviationsmentioning

confidence: 99%

Extra-hepatic cancers in metabolic fatty liver syndromes

Lonardo

2023

Explor Dig Dis

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The liver operates an array of vital digestive, metabolic, immunological, and purificatory physiological functions including synthesis of albumin, regulation of glucose and lipid homeostasis, detoxification of ammonia and xenobiotics, choleresis and production of hepatokines and hormones [1]. However, in healthy states, it is not involved in the storage of fatty substrates and, whenever the normal liver threshold is exceeded, accumulated triglycerides will impair whole-body insulin sensitivity, trigger sterile low-grade hepatic metaflammation, and promote the progression of the fibrosing process that will eventually conduce to cirrhosis in a subset of individuals [2,3]. While the histopathological cascade described above was first recognized in the 1800s by distinguished liver pathologists, such as Addison, Rokitansky, Pepper, and Bartolow, until the years 1958-1971 the debate, with the contributions by Zelman and Thaler, mainly focused on such hepato-histopathological changes being indistinguishable irrespective of the inciting triggers: alcohol, obesity, and diabetes [4]. From the perspective of clinical nosography, this finding eventually led to coining the innovative definitions of "nonalcoholic steatohepatitis (NASH)" and "nonalcoholic fatty liver disease (NAFLD)" in the 1980s. "Nonalcoholic" is a composite word that, at least in the spelling used by Ludwig et al., and by Schaffner and Thaler; does not require any hyphens [4] at variance with the use that is sometimes encountered in contemporary literature ("non-alcoholic").To convert a "negative" definition (i.e., nonalcoholic) into a positive diagnosis highlighting the pathogenic (dysmetabolic) origin, while also avoiding stigmatizing alcohol consumption, a panel of international experts have proposed renaming NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD). Although endorsed to an unprecedented extent [5], MAFLD retains some elements of ambiguity and amplifies NAFLD's heterogeneity, therefore creating major implications for research arena and clinical practice [6,7].Compared to the history of NAFLD briefly summarized above, the notions that NAFLD and NAFLD-related metabolic conditions could also be a risk factor for the development of primary liver cancer (PLC) in a limited proportion of individuals are more recent (Table 1) [8-13].While it is logical and somewhat foreseeable that PLC may eventually develop in some individuals with NAFLD, more recent observations substantiate the probably unexpected theory that, further to PLCs, NAFLD

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“…This sub-grouping of patients may help in defining the heterogeneity of NAFLD. Dietary habits, physical activity, genetic, epigenetic, and immunological factors contribute to NAFLD heterogeneity [ 5 ]. Identification of these additional factors that could modulate the clinical outcomes of NAFLD may help in understanding the disease heterogeneity and approaches to personalized medicine.…”

Section: Introductionmentioning

confidence: 99%