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the evolution, over time, of our understanding of the association of NAFLD with metabolic syndrome, spanning from the outdated concept of “NAFLD as a manifestation of the Metabolic Syndrome”, to the more appropriate consideration that NAFLD has, with metabolic syndrome, a mutual and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.

Highlights

  • 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

  • A retrospective analysis yielded 49 cases of Nonalcoholic steatohepatitis (NASH) out of 543 liver biopsies diagnosed as alcoholic hepatitis

  • Forty-two NASH patients were followed for a median of 4.5 yrs

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Summary

Introduction

Definition Formerly named nonalcoholic fatty liver disease (NAFLD), the spectrum of fatty liver disorders not resulting from alcohol abuse, viral, autoimmune, drug-induced and genetic etiologies, has recently been renamed metabolic (dysfunction) associated fatty liver disease (MAFLD) [1]. Obesity is an independent predictor of disease, accounting for the incremental changes in NAFLD over time in the USA [23]. As a result of its epidemic distribution, NAFLD has become a major clinical and public health issue worldwide [26,27,28,29,30,31]

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