Abstract
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.
Highlights
Definitions and historyNonalcoholic fatty liver disease (NAFLD) is a clinico-pathological syndrome which covers a large gamut of hepatic and extra-hepatic manifestations and complications associated with and predisposing to either individual features of the metabolic syndrome (MetS) [typically type 2 diabetes (T2D) and obesity] or to the full-blown MetS [1,2,3,4,5,6,7]
Over the last 20 years, nonalcoholic fatty liver disease (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
A study supporting the notion that genetic and metabolic drivers dictate the severity of NAFLD as well as indicating a novel risk stratification based on pathogenic determinants of disease
Summary
Nonalcoholic fatty liver disease (NAFLD) is a clinico-pathological syndrome which covers a large gamut of hepatic and extra-hepatic manifestations and complications associated with and predisposing to either individual features of the metabolic syndrome (MetS) [typically type 2 diabetes (T2D) and obesity] or to the full-blown MetS [1,2,3,4,5,6,7]. The epidemiological surge of NAFLD is, at least in part, spurious, [i.e. fuelled by our ever increasing ability to discover this common condition in asymptomatic individuals as well as in cases of otherwise “cryptogenic” cirrhosis and hepatocellular carcinoma (HCC)] [8, 9] and, to a larger extent, due to (western-type) lifestyle and lifestyle changes (in developing countries) [10] Irrespective of this academic contention (spurious phenomenon versus true increase), hard data support the notion that NAFLD accounts for > 30% of deaths due to liver disease and diabetes and ~8% of all-cause mortality in the USA [11]. Additional aspects of NAFLD’s history have been focused in their excellent article by Fouad et al [15]
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