Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science

Abstract

Metabolic (dysfunction)-associated fatty liver disease (MAFLD) affects a third of the population and is a leading cause of liver-related death. Since no effective treatments exist, novel approaches to drug development are required. Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments. An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease (NAFLD) to MAFLD, including a proposal for how the disease should be diagnosed. As allies with the many stakeholders in MAFLD care-including patients, patients' advocates, clinicians, researchers, nurse and allied health groups, regional societies, and others-we are aware of the negative consequences of the NAFLD term and definition. We share the sense of urgency for change and will act in new ways to achieve our goals. Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends, the MAFLD initiative provides a firm foundation to build on. It provides a roadmap for moving forward toward more efficient care and affordable, sustainable drug and device innovation in MAFLD care. We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe's largest and costliest public health burdens. From this viewpoint, we have revisited this initiative through the perspectives of drug development and regulatory science.

MAFLD: How is it different from NAFLD?

“…Positive Diagnostic Criteria -Less Confounding Bias in Patient Selection for Research When selecting patients for fatty liver disease trials, there is confounding bias associated with the NAFLD terminology [58]. Whilst the exclusionary criteria of alcohol and other contributory liver diseases are standard, there is no mechanism to explore the pathogenic aspects of the underlying liver fat infiltration.…”

Editorial: The Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD) Debate: Why the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) Consensus Process is Not Representative

“…Importantly, if the coordinating group of a process expresses views that favor one side or another on social media platforms and other channels, they may lose the objectivity required to obtain true consensus [ 21 , 22 ]. In contrast, the definition of MAFLD was agreed upon scientifically and objectively, without confounding complex regional and national confounders [ 1 , 7 , 14 ]. Currently, the debate that has arisen following the AASLD/EASL consensus continues to drive inertia and controversy.…”

MAFLD: what 2 years of the redefinition of fatty liver disease has taught us

“…and patient groups. [16][17][18][19][20][21][22][23][24][25][26] The need for a such a new definition is also strongly supported by many pathophysiological aspects. 27 Evidence that the new definition 'MAFLD' might advance the field of fatty liver diseases The term 'MAFLD' has been introduced in 2020 and has been increasingly used in the medical literature in the past 2 years (Table 1).…”

“…Although the new definition MAFLD is currently not accepted globally and has raised some criticisms, the new name ‘MAFLD’ has been endorsed in the last 2 years by many international societies and patient groups. 16 – 26 The need for a such a new definition is also strongly supported by many pathophysiological aspects. 27 …”