Fatty Liver Index (FLI) is the best score to predict MASLD with 50% lower cut-off value in women than in men

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined by the presence of hepatic steatosis, detected on ultrasonography (US) imaging or histology, and at least one of criteria for Metabolic Syndrome diagnosis. Simple non-invasive tests (NITs) have been proposed as an acceptable alternative when US and biopsy are not available or feasible but have not been validated for MASLD. In this observational study, we investigated the reliability of NITs for MASLD detection and whether sex-differences in screening methods should be considered.

Methods: We included 1069 individuals (48% males and 52% females) who underwent their first clinical examination for Metabolic Syndrome in the period between January 2015 and December 2022. Liver steatosis was detected through US and anthropometric and clinical parameters were recorded.

Results: Liver steatosis was detected in 648 patients and MASLD was diagnosed in 630 subjects (355 males; 275 females). Women with MASLD showed better metabolic profile and lower prevalence of Metabolic Syndrome criteria than men. Among NITs, Fatty Liver Index (FLI) showed the best ability for detection of MASLD, with a cut-off value of 44 (AUC = 0.82). When considering the two sexes for MASLD detection via FLI, despite no substantial differences regarding FLI correlations with metabolic biomarkers except for age, women showed marked lower FLI cut-off value (32; AUC = 0.80) than men (60; AUC = 0.80).

Conclusions: In this study, we found that FLI is the best non-invasive predictor of both liver steatosis and MASLD. The finding that in women FLI cut-off value for MASLD detection is 50% lower than in men suggests the need of a sex-specific personalized program of screening and prevention of dysmetabolism-related liver diseases, despite outwardly healthy biomarkers profile.

Keywords: Gender difference; Gut-liver axis; Liver steatosis; MASLD; Metabolism; Non-invasive tests.

Fig. 1

Metabolic biomarkers comparisons between males and females with MASLD. The box plots show the median (second quartile), first and third quartile, whiskers go 1.5 times the interquartile distance or to the highest or lowest point, whichever is shorter. Any data beyond these whiskers are shown as points. CMDS is a questionnaire containing eleven food categories, including chronobiology of dietary habits and physical activity that we previously validated for assessing adherence to Mediterranean Diet and lifestyle. Lower CMDS scores indicates poorer adherence. Comparisons were performed by Mann–Whitney test. Statistical significance was assessed for p-values (p) < 0.05; *p < 0.05; ****p < 0.0001. M males, F females, BMI Body Mass Index, WC Waist Circumference, FPG Fasting Plasma Glucose, CMDS Chrono Med Diet Score, AST aspartate transaminase, ALT alanine transaminase, GGT Gamma-glutamyl transferase

Fig. 2

Comparison of empirical ROC curves of non-invasive tests (NITs) in prediction of liver steatosis and MASLD. ROC curves of NITs for prediction of liver steatosis assessed by ultrasound (a) and MASLD (b). The tables (c, d) show empirical estimation of area under curve (AUC) with 95% CI (confidence interval) and p-value for each NITs. Statistical significance was assessed for p-values (p) < 0.05. US ultrasound, FLI Fatty Liver Index, HIS Hepatic Steatosis Index, VAI Visceral Adiposity Index, NFS NAFLD Fibrosis Score, NAFLD-FAT NAFLD-Liver Fat Score, BAAT BMI-ALT-Age and Triglycerides, AAR AST to ALT Ratio, AARPRI (AST to ALT ratio) to Platelet Ratio Index, mFIB-4 modified FIB-4, APRI AST to Platelet Ratio Index, FIB-4 Fibrosis-4 index, API Atherosclerosis Plasma Index, mAPRI modified APRI, NS not-significant

Fig. 3

Correlations between FLI and metabolic biomarkers in men and women. FLI Pearson’s correlations (r) and p-values (p) with age (a), FPG (b), AST (c), ALT (d), Total Cholesterol (e), HDL Cholesterol (f), LDL Cholesterol (g) in two sexes are reported. BMI Body Mass Index, FPG Fasting Plasma Glucose, AST aspartate transaminase, ALT alanine transaminase; ns, not-significant

Fig. 4

Comparisons of non-invasive tests (NITs) ROC curves for MASLD detection in men and women. ROC curves of NITs for detection of steatosis in men (a) and women (b). The table (c) shows empirical estimation of area under curve (AUC) with 95% CI (confidence interval) and p-value, cut-off values with related sensitivity, specificity, and Youden’s Index (YI)