Time to transition from a negative nomenclature describing what NAFLD is not, to a novel, pathophysiology-based, umbrella classification of fatty liver disease (FLD).

Non-alcoholic fatty liver disease (NAFLD) is a definition of a prevalent condition that has been given a name describing what the disease is not, mainly due to gaps in the physiopathological understanding of NAFLD when the name was given to it. NAFLD still remains an unmet clinical need to a large extent due to the heterogenicity of the disease and the lack of a more accurate physiology-based classification. In essence, fatty liver disease (FLD) has a multifactorial etiology, including metabolic abnormalities, environmental influences, genetic disorders, and/or their overlap which makes it difficult to diagnose, design appropriate trials for it and treat this disease. Therefore, we propose herein that as our knowledge about this disease continues to grow exponentially, it is time to consider ending this unspecific, negative and broad classification of NAFLD, and turn it into a positive and targeted one describing what the disease is and not what it is not. Thus, we propose the novel FLD "Mantzoros classification". This innovative classification proposes to classify the heterogeneous causes of FLD under one umbrella and eventually lead to a better nomenclature and classification system reflecting pathophysiology. This in turn could lead to both better clinical trials and more personalized care. An additional aim is to generate a dialogue among the experts in this field to eventually reach the right nomenclature for an appropriate disease classification that would facilitate our understanding, approach, diagnosis, and management of this epidemic of FLD. Overall, a novel classification, based on phenotypic manifestations, leading risk factors and probable causes of FLD, could help our understanding and clinically would be accurately defining and differentiating the disease, leading to a more accurate design and execution of clinical trials. This would in turn lead to tangible benefits for all patients suffering from FLD through targeted and more effective personalized treatments.