LAUSR

Following the worldwide epidemics of obesity and metabolic disorders, and thanks to the recent therapeutic advancements in the field of viral hepatitis, fatty liver disease (FLD) is taking the scene as leading cause of liver-related morbidity and mortality.1,2 Traditionally, FLD has been classified as nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD) and fatty liver due to secondary and uncommon causes. However, converging evidence from epidemiological, genetics, pathophysiological and therapeutic studies published in the last few months has refocused the attention on the metabolic component of FLD, highlighting hepatic fat accumulation as the common denominator of this condition independently of the triggers.3,4 Due to the frequent coexistence of dysmetabolism and at-risk drinking, the difficulty in accurately assessing alcohol intake, the synergy among risk factors in determining FLD, and last but not least the possible role of endogenous alcohol production in non-drinkers,5 an international consensus panel has recently suggested to overcome the NAFLD/ALD dichotomy, converging on metabolically associated FLD (MAFLD) as the most appropriate umbrella term to define FLD associated with metabolic comorbidities.6 This new positive definition of what we still use to call ‘NAFLD’, based on the classification of causes rather than on a frequently inaccurate guess of the absence of just one risk factor, will hopefully improve phenotyping, thereby facilitating the discovery of new biomarkers and treatments.6 In parallel, a causal role for both quantitative and qualitative alterations of hepatic fat in determining progressive liver disease has imposed itself in view of the latest genetics findings,3-4,7,8 However, controversy still remains as to whether reduction in the quantity of hepatic fat can be used as therapeutic target.9 The detrimental impact of excessive liver fat seems to extend to the development of insulin resistance and type 2 diabetes (T2D),7,10,11 while the independent effect on cardiovascular disease remains controversial.10,12 On the other hand, the classical classification of NAFLD based on the dichotomy ‘uncomplicated steatosis/NASH’ 13 cannot improve prognosis prediction over fibrosis stage.14,15 This was also demonstrated in a perspective analysis of a large cohort NAFLD patients from Sweden.16 Within this context, Nasr et al from the same Swedish research group now report that, in 129 patients with biopsy proven NAFLD prospectively re-evaluated on two occasions, the severity of hepatic fat accumulation was able to predict both T2D development in those who were free at baseline, and the overall survival.17 Remarkably, automated quantification of hepatic fat by stereological point counting (SPC) predicted these outcomes independently of adiposity, histological steatosis grade, and also of hepatic inflammation and fibrosis. Furthermore, SPC reduction at follow-up was associated with protection against T2D development,17 thereby further supporting the utility of hepatic fat as clinical outcome. Despite the detailed characterization and prospective assessment of cases at multiple time points, limitations of this study include the monocentric design, limited sample size, and lack of independent