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 Unfortunately, outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments.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.

Keywords: Fatty liver disease; Fibrosis; Liver; MAFLD; NAFLD; NASH.

Fig. 1. Negative implications of the NAFLD term and definition on patients’ recruitment and retention in clinical trials.

Fig. 2. One-size-fits-all approach of clinical trials in the era of NAFLD and proposed personalized trials in the era of MAFLD.

Fig. 3. Redefinition of fatty liver disease from NAFLD to MAFLD can guide drug repurposing in fatty liver disease.

MAFLD is a multisystem disease with links to other metabolic disorders, such as diabetes, cardiovascular disease, and chronic kidney disease. MAFLD will bring fatty liver disease closer to other metabolic diseases and enhance understanding of the shared pathways and phenotypes between MAFLD and these related metabolic disorders that are usually investigated in larger cohorts, which can ultimately help in drug repurposing.