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

Abstract

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.

Keywords: Cardiovascular disease; Diabetes; Endocrine; Fatty liver; Hepatic fibrosis; Hepatocellular carcinoma (HCC); Insulin resistance; Metabolic syndrome; Obesity; Steatosis.

Fig. 1

Causal factors, protective factors and the continuum spectrum of natural history of non-alcoholic fatty liver disease (NAFLD). Factors on the left have an established association with NAFLD and NASH progression. They are broadly classified into genetic factors, comorbid illness, and environmental factors. On the right, factors have a protective role. F0–F4, fibrosis scores (potentially reversible)

Fig. 2

A The flowchart depicts the essential steps involved in the positive diagnosis of MAFLD vs. the diagnosis of NAFLD which requires the exclusion of secondary causes. Adapted from [10, 134]. B Exclusive and overlapping features in the spectrum of definitions ranging from non‐alcoholic fatty liver disease (NAFLD) to metabolic-dysfunction‐associated fatty liver disease (MAFLD). Significant alcohol intake is ≥ 30 g/day and ≥ 20 g/day in men and women, respectively

Fig. 3

Venn diagrams summarizing the current debate about the nomenclature of NAFLD in relation to other causes of fatty liver disease (FLD). The paradigm shifts from a diagnosis of exclusion («non-alcoholic») to active pathophysiologically established diagnoses involving alcohol abuse, metabolic, genetic, lipodystrophic, combined and yet-to-be-defined causes. AAFLD alcoholic-associated fatty liver disease, CAFLD combined causes of FLD, GAFLD genetics-associated fatty liver disease, LAFLD lipodystrophy-associated fatty liver disease, MAFLD metabolic-associated fatty liver disease, NAFLD non-alcoholic fatty liver disease, XAFLD yet-to-be-defined subgroups