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Recently, Arrese and Colleagues have published a review article entitled, “Insights into Nonalcoholic Fatty-Liver Disease (NAFLD) Heterogeneity” (Semin Liver Dis. 2021;41:421-34. doi: 10.1055/s-0041-1730927). This milestone publication clearly and exhaustively explains the multitude of pathogenic pathways involved in the development and progression of disease eventually conducive to heterogeneous clinical phenotypes and different disease outcomes. The present commentary first briefly discusses the biological grounds of NAFLD heterogeneity and then illustrates the work by Arrese et al. In conclusion, the presently adopted nomenclatures appear inadequate in rendering the complexity of disease in the individual patient. In order to adopt the principles of personalized care, what remains to be done is to propose and validate a simple and accurate classification system. This should give full consideration to the principal disease modifiers and should shape a scheme to be adopted in both clinical practice and in the research arena. Care should be taken to not neglect the systemic nature of disease.

Separating the apples from the oranges: from NAFLD heterogeneity to personalized medicine