Open Issues in the Transition from NAFLD to MAFLD: The Experience of the Plinio Study

Abstract

Metabolic associated fatty liver diseases (MAFLD) definition was proposed to identify fatty liver condition associated to metabolic disorders and to replace non-alcoholic fatty liver disease (NAFLD). We aimed to explore the effect of the application of the new MAFLD criteria on a pre-existing cohort of NAFLD patients. The consequences of the reclassification were investigated by applying the MAFLD criteria to a prospective cohort (The Plinio Study) of dysmetabolic patients examined for the presence of NAFLD. In the Plinio cohort, 795 patients had NAFLD and 767 of them (96.5%) were reclassified as MAFLD patients. Out of these, 94.9% had overweight/obesity or diabetes, while the remaining were lean and had metabolic dysregulation defined by the presence of at least two metabolic risk abnormalities. By contrast, 3.5% of the NAFLD patients were reclassified as no-MAFLD due to the absence of overweight/obesity, diabetes, or metabolic risk abnormalities. The only significant difference between the NAFLD and MAFLD groups was the higher prevalence of subjects with BMI ≥ 25 kg/m2 in the latter (88.6% vs. 92%; p = 0.018). In the cohort, 68 subjects were defined as “lean NAFLD”. Of these, 40 were reclassified as MAFLD and 28 as no-MAFLD. In conclusion, when applying MAFLD criteria to the Plinio cohort, there is a substantial overlap between NAFLD and MAFLD diagnosis. However, some specific subgroups of patients, such as those currently defined as lean NAFLD, were excluded by the new MAFLD definition.

Heterogeneity of non-alcoholic fatty liver disease (NAFLD): Implication for cardiovascular risk stratification

“…However, many lines of evidence have proved that these patients might have metabolic dysfunction (e.g. : insulin resistance, diabetes, hypertension [55]) and, based on these cardio-metabolic risk profiles, might be included in the new MAFLD definition [56]. Not by chance, lean NAFLD patients have similar risk to develop cardiometabolic and liver complications as compared to obese ones [57].…”

MAFLD: How is it different from NAFLD?

“…When examining retrospective data comparing the two diagnoses, the majority of patients fulfill both the MAFLD and NAFLD criteria. However, there is a small proportion of patients who make up the non-MR NAFLD group across these studies, ranging from 0.6–16.1%, with most consistently estimating this group to make up around 5% of the fatty liver disease population [ 20 , 22 , 32 , 33 , 40 - 43 ]. While most risks were associated with MAFLD diagnosis, some studies did show that non-MR NAFLD patients had increased risks of cardiovascular disease during follow-up, though the majority of studies showed no increase in liver-related risk compared to the control populations [ 39 ].…”

Function of proprotein convertase subtilisin/kexin type 9 and its role in central nervous system diseases: An update on clinical evidence

“…Hypercholesterolemia is characterized by elevated serum LDL‐C levels and a significantly increased risk of coronary heart disease (Baratta et al, 2023). Under physiological conditions, LDL‐C binds to the LDLR receptor on the surface of liver cells and enters the liver cells, while LDL‐C is degraded in the intracellular lysosome, and LDLR is recycled back to the cell membrane.…”

“…Hypercholesterolemia is an important cause of atherosclerosis, and lowering cholesterol is a preventive strategy. Low‐density lipoprotein cholesterol (LDL‐C) is the main driving factor for the formation, occurrence and development of atherosclerosis, which level is related to cardiovascular risk in a dose‐dependent manner (Baratta et al, 2023). Drugs targeting the regulation of LDL‐C, such as hydroxymethylglutaryl Coenzyme A (HMG‐CoA) reductase inhibitors and cholesterol absorption inhibitors, have been used clinically for many years, but their effectiveness is limited or some patients are intolerant (El Hussein et al, 2023).…”