History of Nonalcoholic Fatty Liver Disease

Abstract

Based on the assumption that characterizing the history of a disease will help in improving practice while offering a clue to research, this article aims at reviewing the history of nonalcoholic fatty liver disease (NAFLD) in adults and children. To this end, we address the history of NAFLD histopathology, which begins in 1980 with Ludwig’s seminal studies, although previous studies date back to the 19th century. Moreover, the principal milestones in the definition of genetic NAFLD are summarized. Next, a specific account is given of the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of “NAFLD as a manifestation of the Metabolic Syndrome”, to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and bi-directional relationship. In addition, we also report on the evolution from first intuitions to more recent studies, supporting NAFLD as an independent risk factor for cardiovascular disease. This association probably has deep roots, going back to ancient Middle Eastern cultures, wherein the liver had a significance similar to that which the heart holds in contemporary society. Conversely, the notions that NAFLD is a forerunner of hepatocellular carcinoma and extra-hepatic cancers is definitely more modern. Interestingly, guidelines issued by hepatological societies have lagged behind the identification of NAFLD by decades. A comparative analysis of these documents defines both shared attitudes (e.g., ultrasonography and lifestyle changes as the first approaches) and diverging key points (e.g., the threshold of alcohol consumption, screening methods, optimal non-invasive assessment of liver fibrosis and drug treatment options). Finally, the principal historical steps in the general, cellular and molecular pathogenesis of NAFLD are reviewed. We conclude that an in-depth understanding of the history of the disease permits us to better comprehend the disease itself, as well as to anticipate the lines of development of future NAFLD research.

Prevalence of nonalcoholic fatty liver disease in mental disorder inpatients in China: an observational study

“…The prevalence of NAFLD was especially high when schizophrenia comorbid with diabetes (41.33%). Our result was consistent with the previous studies, which showed that diabetes and other metabolic dysfunction were risk factors of NAFLD [ 11 , 12 ]. The association of NAFLD with metabolic syndrome was mutual and bi-directional [ 12 ].…”

“…Our result was consistent with the previous studies, which showed that diabetes and other metabolic dysfunction were risk factors of NAFLD [ 11 , 12 ]. The association of NAFLD with metabolic syndrome was mutual and bi-directional [ 12 ]. Recent study demonstrated that NAFLD was an early predictor of metabolic dysfunction, even in healthy populations without metabolic dysfunction [ 35 ].…”

“…NAFLD is closely associated with metabolic syndrome, obesity, type 2 diabetes, and dyslipidemia [ 8 – 10 ]. As the epidemics of obesity and type 2 diabetes increase worldwide, NAFLD is increasing proportionately, and has become a major public health issue worldwide [ 11 , 12 ].…”

Renaming NAFLD to MAFLD: Could the LDE System Assist in This Transition?

“…NAFLD, comprising the whole gamut of alcohol-like liver lesions (i.e., steatosis, steatohepatitis with/without fibrosis, cirrhosis and hepatocellular carcinoma (HCC)) though observed in the nonalcoholic [ 14 ], was formerly believed to be “the hepatic manifestation of the Metabolic Syndrome”. However, this old notion is, at best, incomplete and accumulating data strongly indicate that the association of NAFLD with Metabolic Syndrome is indeed mutual and bi-directional [ 15 , 16 , 17 ].…”

“…As alluded to above, a consistent body of evidence supports the notion that a bi-directional relationship links NAFLD with (features of) Metabolic Syndrome, with insulin resistance being the shared common pathophysiological denominator [ 48 ]. In the medical literature, the historical “chicken and egg” debate regarding the chronological association of NAFLD with Metabolic Syndrome, [ 41 ] eventually found its answer through novel data showing that NAFLD is both the cause and the effect of the Metabolic Syndrome (reviewed in [ 16 , 17 ]). However, it soon became clear that addressing the key pathogenic determinants of NASH would not necessarily improve disease outcomes.…”