Exploration of Digestive Diseases

Table 1. Synopsis of published comparative studies, ordered chronologically

Author, year [Ref]	Method	Results	Conclusion
Zhao and Deng, 2024 [45]	13,856 adults were identified using the NHANES III database and followed for 23.7 ± 7.62 years. Of these, 10,940 had non-MASLD/MAFLD, 855 MAFLD-only, 93 MASLD-only, and 1,968 had overlapping MASLD/MAFLD.	Subjects with MAFLD-only (aHR: 1.151, 95% CI: 1.030–1.285) and overlapping MASLD/MAFLD (aHR: 1.109, 95% CI: 1.033–1.292) had a higher risk of all-cause mortality than individuals with non-MASLD/MAFLD. However, MASLD-only individuals were not at increased risk of all-cause mortality.	It is MAFLD (not MASLD) that determines the natural course of liver disease.
Ramírez-Mejía et al., 2024 [46]	Cross-sectional analysis of 500 participants.	59.4% of participants were diagnosed as MAFLD+MASLD+, 10.2% as MASLD+ and 30.4% as MAFLD-MASLD-. These variable prevalence rates depended on the detection of individuals with a BMI < 25 kg/m², where MASLD identified the highest number (p < 0.001).	MASLD captures lean individuals better than MAFLD, whereas MAFLD better identifies subjects at a higher risk of liver fibrosis and disease progression.
Zhou et al., 2024 [47]	Retrospective analysis of 92,177 participants with SLD ascertained with USG.	MAFLD-MASLD+ subjects did not exhibit a greater MACE risk than MAFLD-MASLD- individuals, and their risk was significantly lower than that of MAFLD+MASLD+ people (16.2% vs. 5.3%, p < 0.001). Among lean SLD subjects, approximately 10% of cases have MASLD and are not at as high a risk of MACE as those who are MAFLD+MASLD+ (17.7% vs. 5.8%, p < 0.001).	The MASLD definition captures a greater number of individuals. Conversely, the MAFLD nomenclature is more selective in identifying those individuals who are at increased risk of adverse outcomes.
Park et al., 2024 [48]	Among 844 participants, SLD was defined as MRI-PDFF ≥ 5%.	The prevalence rates were as follows: NAFLD 25.9%, MAFLD 29.5%, and MASLD 25.2%.	The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD.
Mori et al., 2024 [49]	Among 15,788 recruited Japanese, clustering analyses were used to investigate the NAFLD and MAFLD nomenclatures.	MASLD and NAFLD shared three clusters: (i) low alcohol consumption with low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunctional glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD was widely shared across all five clusters.	The various SLD nomenclatures provide variable insights into predictive factors and the dynamic disease interplay.
Pan et al., 2024 [50]	6,096 individuals from the 2017 to 2020 NHANES cohort.	Compared to the absence of each condition, MAFLD (OR: 2.14, 95% CI: 1.78–2.57, p < 0.001) was more strongly associated with high ASCVD risk than MASLD (OR: 1.82, 95% CI: 1.52–2.18, p < 0.001). At MLR, MAFLD alone was significantly more strongly associated with a high risk of ASCVD (OR: 2.82, 95% CI: 1.13–7.01, p < 0.03) than MASLD alone.	MAFLD and MASLD are both associated with ASCVD risks. However, MAFLD predicts ASCVD risk better than MASLD.
Kim et al., 2024 [51]	Analysis of 7,811 participants of the 3rd NHANES database and linked mortality through 2019. SLD was identified with USG.	During a median 27.1-year follow-up, the risk of all-cause mortality was HR: 1.23, 95% CI: 1.09–1.38 for MAFLD; HR: 1.13, 95% CI: 1.01–1.27 for MASLD.	MAFLD nomenclature identifies a patient population at higher risk of all-cause mortality than MASLD.
Wu et al., 2024 [52]	Population-based cross-sectional survey of 7,388 Chinese participants.	Cryptogenic SLD and MASLD+MAFLD- patients exhibited milder SLD and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all p < 0.05).	MAFLD identifies subjects with more severe SLD and a higher frequency of liver injury.
Pan et al., 2024 [53]	5,492 participants from the 2017–2020 NHANES database were enrolled. Albuminuria was defined as a urinary albumin-to-creatinine ratio ≥ 3 mg/mmol.	MAFLD+MASLD- individuals exhibited a greater prevalence of CKD (24.7% vs. 8.3%, p < 0.006) and albuminuria (18.6% vs. 5%, p < 0.01) than did those with MAFLD-MASLD+. After adjustment for confounders, MAFLD+MASLD- subjects had a 4.73-fold higher risk of having prevalent CKD than those in the MASLD+MAFLD- group (p < 0.03).	MAFLD nomenclature captures CKD patients better than MASLD.
Pan et al., 2024 [54]	8,317 subjects from the 2017–2020 NHANES database were included. Liver fibrosis ≥ F2 (i.e., “significant fibrosis”) was determined by a median LSM ≥ 8.0 kPa.	Compared to MASLD (OR: 2.63, 95% CI: 2.22–3.11, p < 0.0001), MAFLD (OR: 3.44, 95% CI: 2.88–4.12, p < 0.0001) tended to be more strongly associated with significant fibrosis. Compared to MAFLD-MASLD+ individuals, those with MASLD-MAFLD+ had a 14.28-fold higher risk of significant fibrosis.	The MAFLD nomenclature identifies significant fibrosis more precisely among individuals with SLD.
Bao et al., 2024 [55]	Prospective study enrolling 403,506 participants from the UK Biobank.	MAFLD was associated with a higher risk of vascular dementia (HR: 1.32, 95% CI: 1.18–1.48) but a reduced risk of Alzheimer’s disease. MASLD was associated with an increased risk of vascular dementia (HR: 1.24, 95% CI: 1.1–1.39) but not Alzheimer’s disease. While the effect of MAFLD on vascular dementia was consistent regardless of MASLD presence, Alzheimer’s disease risk was only present in those without MASLD (HR: 0.78, 95% CI: 0.67–0.91).	MAFLD is associated with vascular dementia irrespective of the presence of MASLD, whereas the risks of Alzheimer’s disease were only evident in MASLD- individuals.
Mayén et al., 2024 [56]	Data from 15,784 EPIC (a prospective cohort study of more than 521,324 European participants) were used. SLD was assessed with FLI.	Compared to those without the condition, MAFLD was positively associated with all-cause mortality (HR: 1.39, 95% CI: 1.25–1.55) and so was MASLD (HR: 1.40, 95% CI: 1.26−1.56).	Both MAFLD and MASLD are associated with a higher risk of all-cause mortality compared to non-MAFLD and non-MASLD, respectively. However, this study fails to compare MAFLD vs. MASLD directly.
Pennisi et al., 2024 [57]	Meta-analysis of 21 eligible cohort studies.	Compared to those with NAFLD, MAFLD individuals had significantly higher rates of overall mortality (random-effect OR: 1.12, 95% CI: 1.04–1.21, p = 0.004) and CV mortality (random-effect OR: 1.15, 95% CI: 1.04–1.26, p = 0.004), and a marginal trend towards higher rates of developing CKD (random-effect OR: 1.06, 95% CI: 1.00–1.12, p = 0.058) and EHCs (random-effect OR: 1.11, 95% CI: 1.00–1.23, p = 0.052). In meta-regression analyses, male sex and metabolic comorbidities were the strongest risk factors associated with adverse outcomes in MAFLD vs. NAFLD.	Individuals with MAFLD have higher rates of overall and CV mortality and higher risks of developing CKD and EHC events than those with NAFLD.
Jiang et al., 2024 [58]	Data from 7,791 adults participating in the NHANES III study were analyzed.	Compared to those without any SLD and to MASLD-MAFLD+ individuals, MASLD+MAFLD- subjects were younger and had better metabolic profiles and lower fibrosis stages. Consistently, MASLD+MAFLD- people tended to have lower cumulative incidence of all-cause and CV. Clustering analysis showed that MAFLD-MASLD+ clustered differently from individuals with MASLD-MAFLD+.	MAFLD-MASLD+ individuals exhibit a distinct, clinically heterogeneous phenotype compared to those identified by the MAFLD definition.
Kang et al., 2024 [59]	Cross-sectional, multicenter, retrospective study of 2,906 Koreans who underwent abdominal USG and cardiac CT (2017–2021).	In an ASCVD risk score-adjusted model, both MASLD (aOR: 1.21, 95% CI: 1.02–1.44, p = 0.033) and MAFLD (aOR: 1.20, 95% CI: 1.01–1.42, p = 0.034) were associated with CAC. However, only MASLD was associated with severe CAC (aOR: 1.38, 95% CI: 1.01–1.89, p = 0.041).	MASLD may predict higher ASCVD risk better than MAFLD.
Pan et al., 2024 [60]	1,359 participants aged 12 to 17 years from the 2017–2020 NHANES.	25% of patients who were missed based on the MASLD nomenclature and who met the MAFLD criteria had significant liver fibrosis. MAFLD participants tended to have significantly elevated LSMs compared to those without MAFLD (5.66 ± 2.28 vs. 4.94 ± 1.86, p = 0.06). However, this was not the case for MASLD individuals compared to those without MASLD (5.27 ± 3.10 vs. 5.62 ± 2.12, p = 0.3).	The MASLD criteria overlook several adolescents with severe SLD.
Vaz et al., 2025 [61]	Longitudinal study of a cohort of 1,454 randomly selected community-dwelling adult Australians between 2001 and 2003 and followed for a median of 19.7 years (IQR: 19.1–20.1).	MAFLD remained as a risk factor for all-cause mortality on multivariable models adjusted for lifestyle and socioeconomic variables, but not when adjusted for metabolic risk factors. MALOs were increased in MAFLD (IRR: 3.03, 95% CI: 1.22–8.18) and MASLD (IRR: 2.80, 95% CI: 1.05–7.90). Metabolic risk factors were associated with an increased risk of overall mortality and MALO, and cancer (34.3–34.6%) and CVD (30.1–33.7%) were the most common causes of death in SLD.	MAFLD, but not MASLD, is associated with an increased risk of overall mortality, with the components of the MetS playing a major role in increasing the mortality risk.
Peng et al., 2025 [62]	1,862 eligible individuals from the NHANES 2017–2018 cycle.	The risk of HTN was positively associated with MASLD (OR: 2.892, 95% CI: 2.226–3.756), MetALD (OR: 1.802, 95% CI: 1.355–2.398), MAFLD (OR: 3.455, 95% CI: 2.741–4.354) and NAFLD (OR: 1.983, 95% CI: 1.584–2.484) and the risk of T2DM was positively associated with MASLD (OR: 6.360, 95% CI: 4.440–9.109), MAFLD (OR: 7.026, 95% CI: 4.893–10.090) and NAFLD (OR: 3.372, 95% CI: 2.511–4.528). Similar findings were identified for hyperlipidemia.	MAFLD more effectively identifies subjects who are at increased risk of components of the MetS, such as HTN and hyperlipidemia.
Jin et al., 2025 [63]	340,998 participants of the UK Biobank study were followed over a median of 13.5 years.	MAFLD diabetes subtype (HR: 2.26, 95% CI: 2.17–2.35), regardless of the presence of MASLD and ALD (HR: 1.65, 95% CI: 1.55–1.76), showed the highest risk of CVDs.	Irrespective of the presence of MASLD, MAFLD is associated with CVD outcomes.

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aHR: adjusted hazard ratio; ALD: alcohol-related liver disease; aOR: adjusted odds ratio; ASCVD: atherosclerotic cardiovascular disease; CAC: coronary artery calcification; CKD: chronic kidney disease; CI: confidence interval; CT: computerized tomography; CVD: cardiovascular disease; EHCs: extra-hepatic cancers; EPIC: European Prospective Investigation into Cancer and Nutrition; FLI: fatty liver index; HR: hazard ratio; HTN: arterial hypertension; IQR: interquartile range; IRR: incidence rate ratio; LSM: liver stiffness measurement; MACE: major adverse cardiovascular events; MAFLD: metabolic dysfunction-associated fatty liver disease; MALOs: major adverse liver outcomes; MASLD: metabolic dysfunction-associated; MetALD: MASLD and increased alcohol intake; MetS: metabolic syndrome; MLR: Multiple logistic regression; MRI-PDFF: magnetic resonance imaging-proton density fat fraction; NAFLD: nonalcoholic fatty liver disease; NHANES: national health and nutrition examination survey; OR: odds ratio; SLD: steatotic liver disease; T2DM: type 2 diabetes mellitus; USG: ultrasonography

Declarations

Author contributions

AL, MHZ, and ME: Conceptualization, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

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Amedeo Lonardo who is an Editorial Board Member of Exploration of Digestive Diseases had no involvement in the decision-making or the review process of this manuscript. Other authors declare that there are no conflicts of interest.

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