Metabolic dysfunction-associated steatotic liver disease heterogeneity: Need of subtyping

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread global disease with significant health burden. Unhealthy lifestyle, obesity, diabetes mellitus (DM), insulin resistance, and genetics have been implicated in the pathogenesis of MASLD. A significant degree of heterogeneity exists among each of above-mentioned risk factors. Heterogeneity of these risk factors translates into the heterogeneity of MASLD. On the other hand, MASLD can itself lead to insulin resistance and DM. Such heterogeneity makes it difficult to assess the natural course of an individual with MASLD in clinical practice. At present MASLD is considered as one disease despite the variability of etiopathogenic processes, and we lack the consensus definitions of unique subtypes of MASLD. In this review, pathogenic processes of MASLD are discussed and a need of subtyping is recommended.

Keywords: Metabolic dysfunctions-associated steatotic liver disease; Visceral obesity; Genetics; Diabetes; Insulin resistance

Core Tip: Metabolic dysfunctions-associated steatotic liver disease (MASLD) is a pathogenically heterogeneous disease with dynamic pathological features. The cardiometabolic risk of MASLD varies based on underlying etiopathogenic processes. Four subtypes of MASLD have been identified: Diabetic, non-diabetic (insulin resistance), genetic and mixed. These subtypes have not been clearly defined yet as separate entities. Given such heterogeneity, the behavior and outcome of MASLD in each patient is expected to be different. Therefore, a single drug is not expected to work for all patients with MASLD. The natural history of MASLD subtypes is unknown. There is an unmet need to categorize its subtypes and prospective studies are needed to characterize each subtype.