From “MAFLD” to “MASLD”: was this revolution worth it? A head-to-head real-life comparison of MAFLD and MASLD criteria in estimating liver disease worsening risk in lean and not-lean steatotic patients

Introduction

The potential benefits of adopting Metabolic dysfunction-associated steatotic liver disease (MASLD) rather than Metabolic dysfunction-associated fatty liver disease (MAFLD) diagnostic criteria in defining the disease progression risk of steatotic (SLD) patients have never been prospectively evaluated.

Aim

To compare MASLD and MAFLD criteria in estimating the 5-year risk of advanced chronic liver disease (ACLD) progression and hepatocellular carcinoma (HCC) occurrence in lean (L) and not-lean (NL) SLD patients.

Materials and Methods

Between January 2014 and June 2019, 931 ultrasonographic-defined-SLD patients were recruited, excluding individuals with ACLD, alcoholism, and other causes of steatosis. Baseline biochemical and clinical data were collected, including Liver Stiffness (LSM) (>9.7 kPa= advanced fibrosis-AF; >15 kPa=ACLD) and Controlled-Attenuation-Parameter (CAP) (>293-db/m=Severe-steatosis-S3). Patients were observed annually or semiannually (AF) over 5 years, reassessing LSM, CAP, and HCC occurrence.

In July 2024, based on baseline features, patients were a posteriori subdivided into “L” (Body-Mass-Index<25 kg/m²) (n.134) and “NL” (n.797) and, subsequently, by separately applying MAFLD and MASLD criteria, in L-MASLD (n.18), L-MASLD/MAFLD (n.82), L-MAFLD (n.34) and NL-MASLD (n.60), NL-MASLD/MAFLD (n.581), NL-MAFLD (n.156).

Results

At baseline, no differences in S3 (L, p:0.163; NL, p:0.103) and AF (L, p:0.718; NL, p:0.277) prevalences emerged. A higher 5-year ACLD progression (RR: 1.83, C.I.95%:1.357-2.431, p:0.0002) and HCC occurrence (RR:1.32, C.I.95%:1.032-1.451, p:0.03) risk was reported in NL-MASLD. Contrariwise, L-MAFLD presented a higher risk of ACLD progression (RR:2.11, C.I.95%: 1.171-2.250, p:0.01) and, even not significant, HCC occurrence (RR:1.588, C.I.95%:0.747-2.781, p:0.371). ACLD progression occurred in 33.34% L-MASLD vs 70.59% L-MAFLD (median: 43 vs 45.50 months; p:0.0091).Logistic regression (adjusted for sex, age, diabetes, steatosis, and fibrosis severity) revealed high-sensitivity-C-reactive protein (aOR: 1.21; C.I. 95%: 1.052-2.183; p:0.02) and Homeostatic-model-assessment-for-insulin-resistance(aOR: 1.38; C.I. 95%: 1.151-2.275; p:0.01) as variables significantly associated with ACLD-progression in L-MAFLD.

Conclusions

MASLD criteria better estimate the liver disease progression risk limitedly to SLD-NL patients.