Metabolic dysfunction associated fatty liver disease: The new nomenclature and its impact

Table 1 Overall evaluation of the clinical profile and long-term outcome difference between the patients identified as metabolic dysfunction-associated fatty liver disease and non-alcoholic fatty liver disease (also see Supplementary Tables 1-4 for more details on individual study)

Main outcome	Number of studies	Sample	Conclusion
Hepatic steatosis and fibrosis identification in MAFLD terminology change
Steatosis and fibrosis	10	38686 subjects		MAFLD definition is able to capture more subjects with fatty liver disease
				MAFLD group showed either no difference or higher in fibrosis or liver stiffness compared to NAFLD group
Long-term outcome differences in MAFLD terminology change
All cause mortality risks and cause specific mortality	4	183380 subjects		MAFLD is associated with an increased risk of mortality compared to NAFLD
				MAFLD mortality is largely contributed by the presence of metabolic disorders
All cause mortality risks	1	12878 subjects		MAFLD and NAFLD share similar all-cause mortality risk
				MAFLD mortality is hence likely caused by ALD, while NAFLD mortality seems to be caused by metabolic abnormalities
MAFLD and correlation to non-liver diseases
CVD, ASCVD, cardiovascular events	3	2458240 subjects		The risk of CVD is higher in MAFLD compared to NAFLD
				MAFLD is superior over NAFLD in predicting ASCVD risk, contributed by the presence of metabolic risk factors
Clinical and histopathological features of MAFLD
Risk factors, steatosis, advanced fibrosis	9	237679 subjects		T2DM and obesity are significant drivers of MAFLD pathogenesis
				MAFLD patients had higher BMI, LDL-C and prevalence of T2DM as compared to NAFLD patients
				Older age, females and menopausal status are risks factors for developing MAFLD

CVD: Cardiovascular disease; ASCVD: Atherosclerotic cardiovascular disease; NAFLD: Non-alcoholic fatty liver disease; MAFLD: Metabolic dysfunction-associated fatty liver disease; T2DM: Type 2 diabetes mellitus; BMI: Body mass index; LDL-C: Low-density lipoprotein cholesterol.

Table 2 Studies included for study of metabolic dysfunction-associated fatty liver disease pathophysiology

Ref.	Type of study	Sample	Main outcomes	Results	Conclusion
Taheri et al[29]	Case-control study	968 subjects from Iran	DIS, LIS	Risks of MAFLD (OR): High LIS and DIS > high LIS > high DIS (2.56 vs 1.96 vs 1.84; P < 0.001)	Pro-inflammatory dietary and lifestyle exposures are associated with higher risk of MAFLD regardless of gender. Inflammation may be a primary pathogenic mechanism behind dietary risks of MAFLD development
Mu et al[30]	Case-control study	564 subjects from Xinjiang Uygur Autonomous Region, China	SNP	Risks of MAFLD (OR): PNPLA3 rs738409 CC genotype > MBOAT7 rs64173 TT genotype > STAT3 rs74416 AA genotype (1.402 vs 1.299 vs 0.738; P < 0.005)	The CC genotype of PNPLA3 rs738409 and TT genotype of MBOAT7 rs64173 genes are associated with higher risks of MAFLD. The AA genotype of STAT3 rs744166 gene is associated with lower risks of MAFLD. The genes TM6SF2 rs58542926 and GATAD2A rs4808199 show no significant correlation with MAFLD
Panera et al[31]	Cohort study-retrospective	1111 subjects from Milan, Italy	Hepatic fibrosis	Associations of KLB rs17618244 variant (OR): Hepatic fibrosis (1.23; P = 0.04)	The KLB rs17618244 variant was associated with hepatic fibrosis (P = 0.04) but showed no statistical significance in the correlation with steatosis, inflammation and ballooning (P = 0.37, 0.12, 0.16 respectively)
Oses et al[32]	Cross-sectional study	115 children (8-12 years old)	Fasting blood biochemical parameters, SNP	TG, insulin, HOMA-IR, ALT, AST, GGT, ferritin: MAFLD > non-MAFLD (P < 0.05). Percentage of risk of allele carriers: PNPLA3 rs4823173 > PPARG rs1801282 > PPARG rs13081389, HFE rs1800562 (46% vs 33% vs 21%; P < 0.05)	The genetic risk score based on 4 SNPs associated with MAFLD showed limited discriminatory capacity (67% sensitivity and 65% specificity) and did not improve the accuracy of the prediction protocol for MAFLD developed in the study

DIS: Dietary inflammation score; LIS: Lifestyle inflammation score; OR: Odds ratio; NAFLD: Non-alcoholic fatty liver disease; MAFLD: Metabolic dysfunction-associated fatty liver disease; SNP: Single nucleotide polymorphisms; TG: Triglycerides; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; GGT: Gamma-glutamyl transferase.