Emerging evidence has linked metabolic dysfunction-associated steatotic liver disease (MASLD) with accelerated cognitive decline and dementia. We aimed to investigate the associations of MASLD with volumes of total brain tissue and subcortical grey matter, and white matter microstructures in the UK Biobank.

This cross-sectional study included 29,195 individuals (aged 45-82 years) from the UK Biobank who undertook a magnetic resonance imaging (MRI) sub-study between 2014 and 2022. The brain MRI covers three modalities (T1, T2 FLAIR, and diffusion). Volumes of grey matter, subcortical grey matter structures, and regional cortex were derived from T1-weighted images. Fractional anisotropy (FA) and mean diffusivity (MD) were derived from diffusion tensor imaging (DTI) to assess global and tract-specific microstructure. MASLD was defined as the MRI-derived proton density fat fraction (MRI-PDFF) ≥5% and the presence of at least one cardiometabolic criterion. Data were analysed using multiple linear regression models.

MASLD was significantly associated with smaller volumes of total grey matter and subcortical grey matter (p < 0.05) and reduced Alzheimer's disease (AD)-signature cortical thickness (multivariable-adjusted β = -0.04; 95% confidence interval [CI]: -0.07, -0.01). Having MASLD was associated with higher total white matter hyperintensity (WMH) volume (multivariable-adjusted β = 0.12; 95% CI: 0.10, 0.15). For white matter microstructure, MASLD was associated with increased global FA (multivariable-adjusted β = 0.05; 95% CI: 0.03, 0.08) and reduced global MD (multivariable-adjusted β = -0.04; 95% CI: -0.07, -0.01).

Brain morphology associated with MASLD is characterized by smaller subcortical grey matter volume and higher coherence but lower magnitudes of white matter microstructure.

Weight reduction through lifestyle, activity, and dietary interventions are the mainstay of initial therapy for metabolic dysfunction associated steatotic liver disease. Data on the relative effectiveness and metabolic pathways linking weight loss and decreased hepatic steatosis are lacking. We sought to identify coordinated changes between the circulating proteome and hepatic steatosis within a randomized clinical trial of alternate day fasting and exercise and prioritize proteins relevant to hepatic steatosis within a broader context using a community cohort.

We quantified a broad cardiometabolic proteome (>300 proteins) in 67 individuals randomized in a 2×2 factorial design to alternate day fasting and exercise before and after the 3-month intervention to identify proteomic signatures of hepatic steatosis (measured by magnetic resonance imaging proton density fat fraction). Then, we analyzed the cross-sectional relationship of overlapping proteins (≈170) with hepatic attenuation (a computed tomographic technique linked to steatosis) in 707 participants from a community cohort. Principal component analysis demonstrated a proteomic signature associated with intrahepatic triglyceride content (Spearman rho=0.55, P<0.001) and insulin resistance (homeostatic model assessment for insulin resistance, Spearman rho=0.39, P=0.001). Changes in this proteomic signature were associated with changes in intrahepatic triglyceride content over the intervention period (beta=0.12, P<0.001). Moreover, cross-sectional analysis of overlapping proteins with hepatic attenuation in the community cohort showed generally, directionally consistent associations with hepatic steatosis.

These findings highlight the potential for broad proteomic profiling in small nutritional interventional studies with serial phenotyping alongside confirmatory large cohort epidemiology to prioritize targets of hepatic steatosis and cardiometabolic risk for mechanistic study.

Metabolism associated fatty liver disease (MAFLD) has emerged as a growing global health challenge with limited effective treatments. Research on nuclear receptors offers promising new therapeutic avenues for MAFLD. The liver X receptor (LXR) has gained attention for its roles in tumors and metabolic and inflammatory diseases; However, its effects on MAFLD treatment remain a subject of debate. This review explores the therapeutic role of LXRα in MAFLD, focusing on its functions in the intestine, hepatic and adipose tissue, and summarizes recent advancements in LXRα ligands over the past five years. In the intestine, LXRα activation enhances the efflux of non-biliary cholesterol and reduces inflammation in the gut-liver axis by regulating intestinal high-density lipoprotein synthesis and its interaction with lipopolysaccharide. In the liver, LXRα activation facilitates cholesterol transport, influences hepatic lipid synthesis, and exerts anti-inflammatory effects. In adipose tissue, LXRα helps delay MAFLD progression by managing lipid autophagy and insulin resistance. Ligands that modulate LXRα transcriptional activity show considerable promise for MAFLD treatment.

To compare the agreement between ultrasound-derived fat fraction (UDFF) with magnetic resonance proton density fat fraction (MRI-PDFF) for quantification of hepatic steatosis and verify its reliability and diagnostic performance by comparing with MRI-PDFF as the reference standard.

This prospective study included a primary analysis of 191 patients who underwent MRI-PDFF and UDFF from February 2023 to February 2024. MRI-PDFF were derived from three liver segment measurements with calculation of an overall median PDFF. UDFF was performed by two different sonographers for each of the six measurements, and the median was taken. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to assess agreement. Receiver operating characteristics (ROC) curves were used to evaluate the diagnostic performance of UDFF in detecting different degrees of hepatic steatosis.

A total of 176 participants were enrolled in the final cohort of this study (median age, 36.0 years; 82 men, 94 women). The median MRI-PDFF value was 11.3% (interquartile range (IQR) 7.5-18.9); 84.7% patients had a median MRI-PDFF value ≥ 6.4%. The median UDFF measured by different sonographers were 9.5% (IQR: 5.0-18.0) and 9.0% (IQR: 5.0-18.0), respectively. The interobserver agreement of UDFF measurement was excellent agreement (ICC = 0.951 [95% CI: 0.934-0.964], p < 0.001). UDFF was positively strongly correlated with MRI-PDFF with ICC of 0.899 (95% CI: 0.852-0.930). The Bland-Altman analysis showed high agreement between UDFF and MRI-PDFF measurements, with a mean bias of 1.7% (95% LOA, -8.7 to 12.2%). The optimal UDFF cutoff values were 5.5%, 15.5% and 17.5% for detecting MRI-PDFF at historic thresholds of 6.4%, 17.4%, and 22.1%, with AUC of 0.851, 0.952, and 0.948, respectively. The sensitivity was 79.2%, 87.5%, 88.9%, and specificity was 81.5%, 90.6%, 90.0%, respectively.

UDFF is a reliable and accurate method for quantification and classification of hepatic steatosis, with strong agreement to MRI-PDFF. The UDFF cutoff values of 5.5%, 15.5%, and 17.5% provide high sensitivity and specificity for the detection of mild, moderate, and severe hepatic steatosis, respectively.

Question Is ultrasound-derived fat fraction (UDFF) reliable for the quantitative detection of hepatic steatosis compared to MRI proton density fat fraction (MRI-PDFF)? Findings UDFF cutoff values of 5.5%, 15.5%, and 17.5% provided high sensitivity and specificity for the detection of mild, moderate, and severe hepatic steatosis, respectively. Clinical relevance UDFF is a reliable and accurate method for quantification and classification of hepatic steatosis, with strong agreement to MRI-PDFF and high reproducibility of liver fat content by different sonographers.

This study aims to explore the characteristics and influencing factors of ultrasound-derived fat fraction (UDFF) in obese patients with polycystic ovary syndrome (PCOS). Evaluate the diagnostic value of UDFF for MAFLD. This study included 124 obese PCOS patients and 106 age- and body mass index (BMI)-matched obese women, collecting clinical data from both groups. Compare the characteristics and related factors of hepatic steatosis between two groups. A total of 124 obese PCOS patients were divided into MAFLD group (n = 64) and no MAFLD group (n = 60). Binary logistic regression was used to analyze the independent risk factors for MAFLD in obese PCOS patients, and Spearman correlation analysis was used to examine the correlation between UDFF and various variables. The MAFLD group was further divided into mild group (S1, n = 16), moderate group (S2, n = 24), and severe group (S3, n = 24). Based on the ultrasound results, draw a receiver operating characteristic curve (ROC) for diagnosing the degree of hepatic steatosis in obese PCOS patients using UDFF. MAFLD was more common in the obese PCOS group than in the simple obese group (51.61% vs. 40.57%, P < 0.05). UDFF is positively correlated with the severity of MAFLD (r = 0.603, P < 0.01). The AUC for diagnosing liver steatosis with S ≥ 1, S ≥ 2, and S = 3 using UDFF is 0.935, 0.951, and 0.916. UDFF has certain diagnostic value for metabolic-related fatty liver disease in obese PCOS patients, and UDFF levels gradually increase with the severity of MAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), encompasses a spectrum of liver diseases characterized by hepatic steatosis, the presence of at least one cardiometabolic risk factor, and no other apparent cause. Metabolic syndrome (MetS) is a cluster of clinical conditions associated with increased risk of cardiovascular disease, type 2 diabetes, and overall morbidity and mortality. This narrative review summarizes the changes in the management of people with MetS and NAFLD/MASLD from screening to therapeutic strategies that have occurred in the last decades. Specifically, we underline the clinical importance of considering the different impacts of simple steatosis and advanced fibrosis and provide an up-to-date overview on non-invasive diagnostic tests (i.e., imaging and serum biomarkers), which now offer acceptable accuracy and are globally more accessible. Early detection of MetS and MASLD is a top priority as it allows for timely interventions, primarily through lifestyle modification. The liver and cardiovascular benefits of a global and multidimensional approach are not negligible. Therefore, a holistic approach to both conditions, MetS and related chronic liver disease, should be applied to improve overall health and longevity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by increased hepatic steatosis with cardiometabolic disease and is a leading cause of advanced liver disease. We review here the genetic basis of MASLD. The genetic variants most consistently associated with hepatic steatosis implicate genes involved in lipoprotein input or output, glucose metabolism, adiposity/fat distribution, insulin resistance, or mitochondrial/ER biology. The distinct mechanisms by which these variants promote hepatic steatosis result in distinct effects on cardiometabolic disease that may be best suited to precision medicine. Recent work on gene-environment interactions has shown that genetic risk is not fixed and may be exacerbated or attenuated by modifiable (diet, exercise, alcohol intake) and nonmodifiable environmental risk factors. Some steatosis-associated variants, notably those in patatin-like phospholipase domain-containing 3 (PNPLA3) and transmembrane 6 superfamily member 2 (TM6SF2), are associated with risk of developing adverse liver-related outcomes and provide information beyond clinical risk stratification tools, especially in individuals at intermediate to high risk for disease. Future work to better characterize disease heterogeneity by combining genetics with clinical risk factors to holistically predict risk and develop therapies based on genetic risk is required.

To compare the diagnostic accuracy and grading ability of ultrasound-derived fat fraction (UDFF), controlled attenuation parameters (CAP), and hepatic/renal ratio (HRR) for hepatic steatosis in metabolic dysfunction-associated steatotic liver disease (MASLD) using magnetic resonance imaging proton density fat fraction (PDFF) as the gold standard.

Patients suspected of having MASLD in our hospital between October 2023 and May 2024 were divided into the MASLD group and the control group. All patients underwent UDFF, CAP, and PDFF examinations. HRR was measured during routine ultrasound examination. In statistical analysis, we initially assessed the correlation between UDFF, CAP, HRR, and general characteristics of subjects with PDFF. Subsequently, receiver operating characteristic curve were employed to evaluate and compare the diagnostic performance of UDFF, CAP, and HRR for different grades of hepatic steatosis in MASLD. Their area under the curve, optimal cut-off value, sensitivity, and specificity were also determined. Finally, predictive factors determined hepatic steatosis in MASLD (PDFF≥6%) were identified through binary logistic regression analysis.

115 individuals were ultimately included in the MASLD group, while 102 were included in the control group. UDFF, CAP, and HRR were all positively correlated with PDFF. Among them, UDFF exhibited the strongest correlation with PDFF (ρ = 0.91). Furthermore, in the comparison of diagnostic efficacy among different grades of hepatic steatosis, UDFF outperformed CAP and HRR (p < 0.05). However, there were no statistically significant differences in AUCs between CAP and HRR across all three grades. The AUCs for UDFF in ≥S1, ≥S2, and ≥S3 were 0.99 (95% CI 0.97 to 1.00), 0.96 (95% CI 0.93 to 0.98), and 0.97 (95% CI 0.94 to 0.99), respectively. The optimal thresholds for UDFF are determined as follows: ≥ 6% for grade S1; ≥ 15% for grade S2; and ≥ 23% for grade S3. Multivariate analysis revealed that only age, UDFF, and CAP were important influencing factors for hepatic steatosis in MASLD.

The diagnostic accuracy of UDFF surpassed that of CAP and HRR in the detection and grading of hepatic steatosis in MASLD.

Amidst the global rise of metabolic dysfunction-associated steatotic liver disease (MASLD), driven by increasing obesity rates, there is a pressing need for precise, non-invasive diagnostic tools. Our research aims to validate MRI Proton Density Fat Fraction (MRI-PDFF) utility, compared to liver biopsy, in grading hepatic steatosis in MASLD.

A systematic search was conducted across Embase, PubMed/Medline, Scopus, and Web of Science until January 13, 2024, selecting studies that compare MRI-PDFF with liver biopsy for hepatic steatosis grading, defined as grades 0 (< 5% steatosis), 1 (5-33% steatosis), 2 (34-66% steatosis), and 3 (> 66% steatosis).

Twenty-two studies with 2844 patients were included. The analysis showed high accuracy of MRI-PDFF with AUCs of 0.97 (95% CI = 0.96-0.98) for grade 0 vs ≥ 1, 0.91 (95% CI = 0.88-0.93) for ≤ 1 vs ≥ 2, and 0.91 (95% CI = 0.88-0.93) for ≤ 2 vs 3, diagnostic odds ratio (DOR) from 98.74 (95% CI = 58.61-166.33) to 23.36 (95% CI = 13.76-39.68), sensitivity and specificity from 0.93 (95% CI = 0.88-0.96) to 0.76 (95% CI = 0.63-0.85) and 0.93 (95% CI = 0.88-0.96) to 0.89 (95% CI = 0.84-0.93), respectively. Likelihood ratio (LR) + ranged from 13.3 (95% CI = 7.4-24.0) to 7.2 (95% CI = 4.9-10.5), and LR - from 0.08 (95% CI = 0.05-0.13) to 0.27 (95% CI = 0.17-0.42). The proposed MRI-PDFF threshold of 5.7% for liver fat content emerges as a potential cut-off for the discrimination between grade 0 vs ≥ 1 (p = 0.075).

MRI-PDFF is a precise non-invasive technique for diagnosing and grading hepatic steatosis, warranting further studies to establish its diagnostic thresholds.

This study underscores the high diagnostic accuracy of MRI-PDFF for distinguishing between various grades of hepatic steatosis for early detection and management of MASLD, though further research is necessary for broader application.

MRI-PDFF offers precision in diagnosing and monitoring hepatic steatosis. The diagnostic accuracy of MRI-PDFF decreases as the grade of hepatic steatosis advances. A 5.7% MRI-PDFF threshold differentiates steatotic from non-steatotic livers.

MRI proton density fat fraction (MRI-PDFF), controlled attenuation parameters (CAP), and attenuation coefficients (AC) are capable of steatosis characterization and may be useful as noninvasive alternatives for diagnosing hepatic steatosis.

This meta-analysis aimed to evaluate the performance of MRI-PDFF, CAP, and AC in grading hepatic steatosis, using histology as the reference standard.

We conducted a comprehensive search of the PubMed, Cochrane Library, Embase, and Web of Science databases until June 2024. The quality of eligible studies was assessed. Pooled sensitivity, specificity, and area under receiver operating characteristic (AUC) curves were calculated using a bivariate random-effects model. Meta-regression analysis, subgroup analysis, and Deeks' test were performed to explore heterogeneity and assess publication bias.

This meta-analysis included 38 studies with 5056 patients with metabolic dysfunction-associated steatotic liver disease. The AUC values for grading steatosis ≥S1, ≥S2, and ≥S3 were 0.99, 0.89, and 0.90 for MRI-PDFF, 0.95, 0.84, and 0.77 for CAP, and 0.97, 0.90, and 0.89 for AC, respectively. CAP demonstrated lower accuracy for detecting steatosis grades ≥S2 and ≥S3 compared to MRI-PDFF (0.89 vs. 0.84, p<0.001; 0.90 vs. 0.77, p<0.001) and AC (0.90 vs. 0.84, p<0.001; 0.89 vs. 0.77, p<0.001). Subgroup analyses revealed that MRI-PDFF and CAP exhibited superior diagnostic performance in diagnosing ≥S2 and ≥S3 steatosis among individuals in Asia, with a body mass index ≤30 kg/m2, and age <51 years.

A direct comparison with CAP showed greater accuracy for MRI-PDFF and AC in diagnosing moderate and severe steatosis, and similar diagnostic performance for MRI-PDFF and AC. For patients with steatosis, AC should be incorporated into routine ultrasound screening.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease globally. Based on the 2023 definition, MASLD is characterized by the presence of metabolic dysfunction and limited alcohol consumption (<140 grams/week for women, <210 grams/week for men). Given the significant burden of MASLD in Latin America, this guidance was developed by the Latin American Association for the Study of the Liver (ALEH) Working Group to address key aspects of its clinical assessment and therapeutic strategies. In Latin America, ultrasonography is recommended as the initial screening tool for hepatic steatosis due to its accessibility, while Fibrosis-4 (FIB-4) is preferred for fibrosis risk stratification, with further evaluation using more specific techniques (i.e., vibration-controlled transient elastography or Enhanced Liver Fibrosis [ELF] test). A Mediterranean diet is advised for all MASLD patients, with a target of 7-10% weight loss for those with excess weight. Complete alcohol abstinence is recommended for patients with significant fibrosis, and smoking cessation is encouraged regardless of fibrosis stage. Pharmacological options should be tailored based on the presence of steatohepatitis, liver fibrosis, excess weight, and diabetes, including resmetirom, incretin-based therapies, pioglitazone, and sodium-glucose cotransporter-2 inhibitors. Bariatric surgery may be considered for MASLD patients with obesity unresponsive to lifestyle and medical interventions. Hepatocellular carcinoma screening is advised for all cirrhotic patients, with consideration given to those with advanced fibrosis based on individual risk. Finally, routine cardiovascular risk assessment and proper diabetes prevention and management remain crucial for all patients with MASLD.

Preoperative imaging evaluation of liver volume and hepatic steatosis for the donor affects transplantation outcomes. However, computed tomography (CT) for liver volumetry and magnetic resonance spectroscopy (MRS) for hepatic steatosis are time consuming. Therefore, we investigated the correlation of automated 3D-multi-echo-Dixon sequence magnetic resonance imaging (ME-Dixon MRI) and its derived proton density fat fraction (MRI-PDFF) with CT liver volumetry and MRS hepatic steatosis measurements in living liver donors.

This retrospective cross-sectional study was conducted from December 2017 to November 2022. We enrolled donors who received a dynamic CT scan and an MRI exam within 2 days. First, the CT volumetry was processed semiautomatically using commercial software, and ME-Dixon MRI volumetry was automatically measured using an embedded sequence. Next, the signal intensity of MRI-PDFF volumetric data was correlated with MRS as the gold standard.

We included the 165 living donors. The total liver volume of ME-Dixon MRI was significantly correlated with CT (r = 0.913, p < 0.001). The fat percentage measured using MRI-PDFF revealed a strong correlation between automatic segmental volume and MRS (r = 0.705, p < 0.001). Furthermore, the hepatic steatosis group (MRS ≥5%) had a strong correlation than the non-hepatic steatosis group (MRS <5%) in both volumetric (r = 0.906 vs. r = 0.887) and fat fraction analysis (r = 0.779 vs. r = 0.338).

Automated ME-Dixon MRI liver volumetry and MRI-PDFF were strongly correlated with CT liver volumetry and MRS hepatic steatosis measurements, especially in donors with hepatic steatosis.

The quantity of regions of interest (ROIs) constitutes the primary determinant of the time investment in image analysis. In the context of proton density fat-fraction (PDFF) magnetic resonance imaging (MRI) conducted on liver grafts in ex vivo conditions, this research systematically examines various ROI sampling strategies. The findings of this study furnish essential insights, offering a foundation for optimizing time efficiency while ensuring precise assessment of hepatic steatosis before the crucial process of liver transplantation.

This was a retrospective analysis of a prospective study and included 35 liver grafts with histopathological steatosis that underwent 3T PDFF MRI in ex vivo. One ROI of 1 cm2 was selected for each hepatic segment, and any combination of ROIs in 1-8 liver segments was used, resulting in 511 combinations. Using intraclass correlation coefficients (ICCs) and Bland-Altman analyses, the PDFFs of all these combinations were compared with the 9-ROI average PDFF. There was a moderate correlation between the average PDFF and the histological findings (R = 0.47, P＜0.01).

The average 9-ROI PDFF of all liver grafts was 4.07 ± 4.35 % (0.870-20.904). All strategies with ≥5 ROIs had intraclass correlation coefficient (ICC) ≥ 0.995 and absolute limits of agreement (|LOA|)≤ 1.5 %. Overall, 54 of 84 (67.5 %) 3-ROI sampling strategy had ICC ≥0.995, and 70 of 84 (70 %) had |LOA|≤ 1.5 %. A total of 111 of 126 (88.1 %) 4-ROI sampling strategy had ICC ≥0.995, and 125 of 126 (99.2 %) had |LOA| ≤ 1.5 %.

The employment of the 5-ROI sampling strategy proves instrumental in both time conservation and precise assessment of hepatic steatosis within liver grafts during the ex vivo phase preceding liver transplantation.

Background: Non-alcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide, and dietary interventions have important potential in the prevention and treatment of NAFLD. Moreover, previous animal studies have shown that flaxseed has a good improvement effect in animal NAFLD models. Objectives: Assess whether flaxseed powder could improve the liver lipid content in patients with NAFLD. Methods: In this 12-week randomized controlled clinical trial, 50 patients were randomly assigned to the flaxseed group (n = 25) and the control group (n = 25). The flaxseed group received 30 g d-1 flaxseed powder orally before lunch or dinner along with health education, while the control group received only health education. The primary outcome was the intrahepatic lipid content assessed by the proton density fat fraction estimated by magnetic resonance imaging, and secondary outcomes were body composition measurements, liver function, and glucolipid metabolism. Results: Patients in the flaxseed group showed significantly lower liver fat content, body fat percentage, obesity index, visceral fat area, serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels after a 12-week intervention compared to pre-intervention levels, while serum apolipoprotein A1 (Apo A1) and high-density lipoprotein cholesterol (HDL-C) levels were significantly increased, with all differences being statistically significant (P < 0.05). Analysis of the gut microbiota showed that, at the phylum level, flaxseed intervention significantly increased the abundance of Bacteroides and Actinobacteria, while decreasing the ratio of Firmicutes to Bacteroidetes. At the genus level, the relative abundance of Clostridium_sensu_stricto_1, Parasutterella, Lachnospiraceae_NK4A136_group, Eubacterium_xylanophilum_group, and Bifidobacterium in the gut microbiota of the flaxseed group was significantly higher than that of the control group (P < 0.05), whereas the relative abundance of Coriobacteriaceae_UCG-002 was significantly lower than that of the control group (P < 0.05). Conclusions: Flaxseed powder intervention for 12 weeks had the effect of improving liver lipid deposition, liver function, body composition indicators, and lipid metabolism in patients with NAFLD. It also regulated the gut microbiota in NAFLD patients, increasing the abundance of beneficial bacteria while reducing harmful bacteria. This suggested that flaxseed is one of the natural and effective foods for improving NAFLD.

The liver is a frequent focus in radiology due to its diverse pathology, and artificial intelligence (AI) could improve diagnosis and management. This systematic review aimed to assess and categorize research studies on AI applications in liver radiology from 2018 to 2024, classifying them according to areas of interest (AOIs), AI task and imaging modality used. We excluded reviews and non-liver and non-radiology studies. Using the PRISMA guidelines, we identified 6680 articles from the PubMed/Medline, Scopus and Web of Science databases; 1232 were found to be eligible. A further analysis of a subgroup of 329 studies focused on detection and/or segmentation tasks was performed. Liver lesions were the main AOI and CT was the most popular modality, while classification was the predominant AI task. Most detection and/or segmentation studies (48.02%) used only public datasets, and 27.65% used only one public dataset. Code sharing was practiced by 10.94% of these articles. This review highlights the predominance of classification tasks, especially applied to liver lesion imaging, most often using CT imaging. Detection and/or segmentation tasks relied mostly on public datasets, while external testing and code sharing were lacking. Future research should explore multi-task models and improve dataset availability to enhance AI's clinical impact in liver imaging.

To explore the application of ultrasound derived fat fraction (UDFF) in evaluating metabolic associated fatty liver disease in obese polycystic ovary syndrome.

This study included 124 obese PCOS patients and 106 age and body mass index (BMI) matched non PCOS control group women. The two groups of data were compared to determine the prevalence of metabolic associated fatty liver disease (MAFLD) in PCOS obese patients. The 124 obese PCOS patients were divided into MAFLD group (n = 64) and non MAFLD group (n = 60). Using ROC curve analysis to evaluate the diagnostic performance of UDFF and SWV values for MAFLD. The MAFLD group was divided into mild group (n = 16), moderate group (n = 24), and severe group (n = 24). Use Spearman correlation method to analyze the relationship between UDFF value, SWV value and the severity of MAFLD.

MAFLD was more common in the obese PCOS group than in the control group (51.61 vs 27.36%) (χ2 = 13.9583, P = 0.00019). The UDFF of obese PCOS patients was higher than those of the control group, while SWV was lower than those of the control group. ROC analysis showed that the AUC of UDFF for diagnosing MAFLD was 0.935, with sensitivity, specificity, and cut-off values of 92.2, 85.0, and 4.5%, respectively. UDFF was positively correlated with the severity of MAFLD (r = 0.603, P < 0.01). The AUC of SWE for diagnosing MAFLD was 0.728, with sensitivity, specificity, and cut-off values of 51.6, 93.3%, and 1.015 m/s, respectively. SWV was negatively correlated with the severity of MAFLD (r = - 0.551, P < 0.01).

The prevalence of MAFLD is significantly higher in obese PCOS patients, and UDFF technology can detect and quantitatively analyze liver fat infiltration in obese PCOS patients early. At the same time, auto-pSWE also has diagnostic significance for the progression of liver disease.

Obesity and associated insulin resistance induce a chronic metaboinflammatory state that lead to injury and dysfunction of multiple organs resulting in a cluster of noncommunicable diseases such as type 2 diabetes mellitus, hypertension, cardiovascular disease, chronic kidney disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Metabolic dysfunction-associated steatohepatitis (MASH) is a histologically active form of MASLD and characterized by greater injury and inflammation and progresses to cirrhosis with greater certainty than steatosis alone. The progression to cirrhosis is characterized by increasing fibrosis. The goal of treatment of MASLD/MASH was to improve the metaboinflammatory state i.e., the root cause of the liver disease and to prevent fibrosis progression to cirrhosis whereas in those who already have cirrhosis need additional care to prevent portal hypertension-related outcomes. Fibrosis regression is thus a key objective of treatment. The recent approval of resmetirom for MASH with fibrosis and the use of glucagon-like peptide-1 receptor agonists for obesity and type 2 diabetes has increased awareness of these NCDs and resulted in the growing demand for liver assessment and care in obese individuals. Patients with MASLD also have multiple metabolic comorbidities which represent competing threats to life, and the care of the patient requires both assessment of the totality of the risk and a more holistic approach integrating the care of all of the threats to life. Here, we provide a pragmatic and easily implementable risk-based approach to the evaluation and management of MASLD.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD), is a chronic liver disorder associated with disturbances in lipid metabolism. The disease is prevalent worldwide, particularly closely linked with metabolic syndromes such as obesity and diabetes. Magnetic Resonance Proton Density Fat Fraction (MRI-PDFF), serving as a non-invasive and highly quantitative imaging assessment tool, holds promising applications in the diagnosis and research of MASLD. This paper aims to comprehensively review and summarize the applications and research progress of MRI-PDFF technology in MASLD, analyze its strengths and challenges, and anticipate its future developments in clinical practice.

Early detection and quantitative evaluation of liver steatosis are crucial. Therefore, this study investigated a method for classifying ultrasound images to fatty liver grades based on echo-envelope statistics (ES) and convolutional neural network (CNN) analyses.

Three fatty liver grades, i.e., normal, mild, and moderate-to-severe, were defined using the thresholds of the magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). There were 10 cases of each grade, totaling 30 cases. To visualize the texture information affected by the deposition of fat droplets within the liver, the maps of first- and fourth-order moments and the heat maps formed from both moments were employed as parametric images derived from the ES. Several dozen to hundreds of regions of interest (ROIs) were extracted from the liver region in each parametric image. A total of 7680 ROIs were utilized for the transfer learning of a pretrained VGG-16 and classified using the transfer-learned VGG-16.

The classification accuracies of the ROIs in all types of the parametric images were approximately 46%. The fatty liver grade for each case was determined by hard voting on the classified ROIs within the case. In the case of the fourth-order moment maps, the classification accuracy of the cases through hard voting mostly increased to approximately 63%.

The formation of parametric images derived from the ES and the CNN classification of the parametric images were proposed for the quantitative diagnosis of liver steatosis. In more than 60% of the cases, the fatty liver grade could be estimated solely using ultrasound images.

Integrating biomarkers into a comprehensive strategy is crucial for precise patient management, especially considering the significant healthcare costs associated with diseases. Current studies emphasize the urgent need for a paradigm shift in conceptualizing nonalcoholic fatty liver disease (NAFLD), now renamed metabolic dysfunction-associated steatotic liver disease (MASLD). Biomarkers are emerging as indispensable tools for accurate diagnosis, risk stratification, and monitoring disease progression. This review classifies biomarkers into conventional and novel categories, such as lipids, insulin resistance, hepatic function, and cutting-edge imaging/omics, and evaluates their potential to transform the approach to MASLD among individuals with type 2 diabetes mellitus (T2D). It focuses on the critical role of biomarkers in early MASLD detection, enhancing predictive accuracy, and discerning responses to interventions (pharmacological or lifestyle modifications). Amid this discussion, the complexities of the relationship between T2D and MASLD are explored, considering factors like age, gender, genetics, ethnicity, and socioeconomic background. Biomarkers enhance the effectiveness of interventions and support global initiatives to reduce the burden of MASLD, thereby improving public health outcomes. This review recognizes the promising potential of biomarkers for diagnostic precision while candidly addressing the challenges in implementing these advancements in clinical practice. The transformative role of biomarkers emerges as a central theme, promising to reshape our understanding of disease trajectories, prognosis, and the customization of personalized therapeutic strategies for improved patient outcomes. From a future perspective, identifying early-stage biomarkers, understanding environmental impact through exposomes, and applying a multiomics approach may reveal additional insight into MASLD development.

Chronic liver disease (CLD) is a global and worldwide clinical challenge, considering that different underlying liver entities can lead to hepatic dysfunction. In the past, blood tests and clinical evaluation were the main noninvasive tools used to detect, diagnose and follow-up patients with CLD; in case of clinical suspicion of CLD or unclear diagnosis, liver biopsy has been considered as the reference standard to rule out different chronic liver conditions. Nowadays, noninvasive tests have gained a central role in the clinical pathway. Particularly, liver stiffness measurement (LSM) and cross-sectional imaging techniques can provide transversal information to clinicians, helping them to correctly manage, treat and follow patients during time. Cross-sectional imaging techniques, namely computed tomography (CT) and magnetic resonance imaging (MRI), have plenty of potential. Both techniques allow to compute the liver surface nodularity (LSN), associated with CLDs and risk of decompensation. MRI can also help quantify fatty liver infiltration, mainly with the proton density fat fraction (PDFF) sequences, and detect and quantify fibrosis, especially thanks to elastography (MRE). Advanced techniques, such as intravoxel incoherent motion (IVIM), T1- and T2- mapping are promising tools for detecting fibrosis deposition. Furthermore, the injection of hepatobiliary contrast agents has gained an important role not only in liver lesion characterization but also in assessing liver function, especially in CLDs. Finally, the broad development of radiomics signatures, applied to CT and MR, can be considered the next future approach to CLDs. The aim of this review is to provide a comprehensive overview of the current advancements and applications of both invasive and noninvasive imaging techniques in the evaluation and management of CLD.

With the rising epidemic of obesity, metabolic syndrome, and type 2 diabetes mellitus in China, metabolic dysfunction-associated non-alcoholic fatty liver disease has become the most prevalent chronic liver disease. This condition frequently occurs in Chinese patients with alcoholic liver disease and chronic hepatitis B. To address the impending public health crisis of non-alcoholic fatty liver disease and its underlying metabolic issues, the Chinese Society of Hepatology and the Chinese Medical Association convened a panel of clinical experts to revise and update the "Guideline of prevention and treatment of non-alcoholic fatty liver disease (2018, China)". The new edition, titled "Guideline for the prevention and treatment of metabolic dysfunction-associated fatty liver disease (Version 2024)", offers comprehensive recommendations on key clinical issues, including screening and monitoring, diagnosis and evaluation, treatment, and follow-up for metabolic dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatotic liver disease. Metabolic dysfunction-associated fatty liver disease is now the preferred English term and is used interchangeably with metabolic dysfunction-associated steatotic liver disease. Additionally, the guideline emphasizes the importance of multidisciplinary collaboration among hepatologists and other specialists to manage cardiometabolic disorders and liver disease effectively.

Provide a concise update on metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), as well as a practical approach to screening and initial evaluation.

Nomenclature changes have placed a greater focus on cardiometabolic risk factors in the definition of MASLD. Screening for MASLD is by stepwise noninvasive serum and imaging tests which can identify patients at risk for advanced fibrosis and liver-related complications. MASLD has been increasing in prevalence and disease burden but is underrecognized in primary care and endocrinology clinics. Multiple society guidelines, synthesized here, provide a framework for the initial approach in the diagnosis and evaluation of MASLD. Recent advances in pharmacologic treatment underline the importance of screening for patients who are at risk for advanced fibrosis as they are most likely to benefit from new drug classes, such as the liver-directed thyroid receptor agonist resmiterom.

This study evaluates the impact of liver steatosis on the discriminative ability for liver fibrosis and inflammation using a novel Dixon water-only fat-corrected Look-Locker T1 mapping sequence, compared with a standard shortened Modified Look-Locker Inversion Recovery (shMOLLI) sequence, with the aim of overcoming the limitation of steatosis-related confounding in liver T1 mapping.

3 T magnetic resonance imaging of the liver including the 2 T1 mapping sequences and proton density fat fraction (PDFF) was prospectively performed in 24 healthy volunteers and 38 patients with histologically proven liver fibrosis evaluated within 90 days of liver biopsy. Paired Mann-Whitney test compared sequences between participants with and without significant liver steatosis (PDFF cutoff 10%), and unpaired Kruskal-Wallis test compared healthy volunteers to patients with early (F0-2) and advanced (F3-4) liver fibrosis, as well as low (A0-1) and marked (A2-3) inflammatory activity. Univariate and multivariate logistic regression models assessed the impact of liver steatosis on both sequences.

Dixon_W T1 was higher than shMOLLI T1 in participants without steatosis (median 896 ms vs 890 ms, P = 0.04), but lower in participants with liver steatosis (median 891 ms vs 973 ms, P < 0.001). Both methods accurately differentiated between volunteers and patients with early and advanced fibrosis (Dixon_W 849 ms, 910 ms, 947 ms, P = 0.011; shMOLLI 836 ms, 918 ms, 978 ms, P < 0.001), and those with mild and marked inflammation (Dixon_W 849 ms, 896 ms, 941 ms, P < 0.01; shMOLLI 836 ms, 885 ms, 978 ms, P < 0.001). Univariate logistic regression showed slightly lower performance of the Dixon_W sequence in differentiating fibrosis (0.69 vs 0.73, P < 0.01), compensated by adding liver PDFF in the multivariate model (0.77 vs 0.75, P < 0.01).

Dixon water-only fat-corrected Look-Locker T1 mapping accurately identifies liver fibrosis and inflammation, with less dependency on liver steatosis than the widely adopted shMOLLI T1 mapping technique, which may improve its predictive value for these conditions.

Background and Objectives: Metabolic syndrome (MetS) is a condition marked by a complex array of physiological, biochemical, and metabolic abnormalities, including central obesity, insulin resistance, high blood pressure, and dyslipidemia (characterized by elevated triglycerides and reduced levels of high-density lipoproteins). The pathogenesis develops from the accumulation of lipid droplets in the hepatocyte (steatosis). This accumulation, in genetically predisposed subjects and with other external stimuli (intestinal dysbiosis, high caloric diet, physical inactivity, stress), activates the production of pro-inflammatory molecules, alter autophagy, and turn on the activity of hepatic stellate cells (HSCs), provoking the low grade chronic inflammation and the fibrosis. This syndrome is associated with a significantly increased risk of developing type 2 diabetes mellitus (T2D), cardiovascular diseases (CVD), vascular, renal, pneumologic, rheumatological, sexual, cutaneous syndromes and overall mortality, with the risk rising five- to seven-fold for T2DM, three-fold for CVD, and one and a half-fold for all-cause mortality. The purpose of this narrative review is to examine metabolic syndrome as a "systemic disease" and its interaction with major internal medicine conditions such as CVD, diabetes, renal failure, and respiratory failure. It is essential for internal medicine practitioners to approach this widespread condition in a "holistic" rather than a fragmented manner, particularly in Western countries. Additionally, it is important to be aware of the non-invasive tools available for assessing this condition. Materials and Methods: We conducted an exhaustive search on PubMed up to July 2024, focusing on terms related to metabolic syndrome and other pathologies (heart, Lung (COPD, asthma, pulmonary hypertension, OSAS) and kidney failure, vascular, rheumatological (osteoarthritis, rheumatoid arthritis), endocrinological, sexual pathologies and neoplastic risks. The review was managed in accordance with the PRISMA statement. Finally, we selected 300 studies (233 papers for the first search strategy and 67 for the second one). Our review included studies that provided insights into metabolic syndrome and non-invasive techniques for evaluating liver fibrosis and steatosis. Studies that were not conducted on humans, were published in languages other than English, or did not assess changes related to heart failure were excluded. Results: The findings revealed a clear correlation between metabolic syndrome and all the pathologies above described, indicating that non-invasive assessments of hepatic fibrosis and steatosis could potentially serve as markers for the severity and progression of the diseases. Conclusions: Metabolic syndrome is a multisystem disorder that impacts organs beyond the liver and disrupts the functioning of various organs. Notably, it is linked to a higher incidence of cardiovascular diseases, independent of traditional cardiovascular risk factors. Non-invasive assessments of hepatic fibrosis and fibrosis allow clinicians to evaluate cardiovascular risk. Additionally, the ability to assess liver steatosis may open new diagnostic, therapeutic, and prognostic avenues for managing metabolic syndrome and its complications, particularly cardiovascular disease, which is the leading cause of death in these patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Performance assessments of quantitative determinations of proton density fat fraction (PDFF) have largely focused on the range between 0 and 50%. We evaluate PDFF in a two-site phantom study across the full 0-100% PDFF range.

We used commercially available 3D chemical-shift-encoded water-fat MRI sequences from three MRI system vendors at 1.5T and 3T and conducted the study across two sites. A spherical phantom housing 18 vials spanning the full 0-100% PDFF range was used. Data at each site were acquired using default parameters to determine same-day and different-day intra-scanner repeatability, and inter-system and inter-site reproducibility, in addition to linear regression between reference and measured PDFF values.

Across all systems, results demonstrated strong linearity and minimal bias. For 1.5T systems, a pooled slope of 0.99 with a 95% confidence interval (CI) of 0.981-0.997 and a pooled intercept of 0.61% PDFF with a 95% CI of 0.17-1.04 were obtained. Results for pooled 3T data included a slope of 1.00 (95% CI 0.995-1.005) and an intercept of 0.69% PDFF (95% CI 0.39-0.97). Inter-site and inter-system reproducibility coefficients ranged from 2.9 to 6.2 (in units of PDFF), while intra-scanner same-day and different-day repeatability ranged from 0.6 to 7.8.

PDFF across the 0-100% range can be reliably estimated using current commercial offerings at 1.5T and 3T.

Bariatric intervention has been reported to be an effective way to improve metabolic dysfunction-associated steatotic liver disease (MASLD) in obese individuals. The current systemic review aimed to assess the changes in MRI-determined hepatic proton density fat fraction (MRI-PDFF) and nonalcoholic fatty liver disease activity score (NAS) after bariatric surgery or intragastric balloon/gastric banding in MASLD patients with obesity.

We searched various databases including PubMed, OVID Medline, EMBASE, and Cochrane Library. Primary outcomes were the changes in intrahepatic fat on MRI-PDFF and histologic features of metabolic dysfunction-associated steatohepatitis (MASH).

Thirty studies with a total of 3,134 patients were selected for meta-analysis. Bariatric intervention significantly reduced BMI (ratio of means, 0.79) and showed 72% reduction of intrahepatic fat on MRI-PDFF at 6 months after bariatric intervention (ratio of means, 0.28). Eight studies revealed that NAS was reduced by 60% at 3-6 months compared to baseline, 40% at 12-24 months, and 50% at 36-60 months. Nineteen studies revealed that the proportion of patients with steatosis decreased by 44% at 3-6 months, 37% at 12-24 months, and 29% at 36-60 months; lobular inflammation by 36% at 12-24 months and 51% at 36-60 months; ballooning degeneration by 38% at 12-24 months; significant fibrosis (≥F2) by 18% at 12-24 months and by 17% at 36-60 months after intervention.

Bariatric intervention significantly improved MRI-PDFF and histologic features of MASH in patients with obesity. Bariatric intervention might be the effective alternative treatment option for patients with MASLD who do not respond to lifestyle modification or medical treatment.

To evaluate the diagnostic performance of attenuation coefficient (AC), hepato-renal index (HRI) and controlled attenuation parameter (CAP) in quantitative assessment of hepatic steatosis by employing histopathology as reference standard.

Participants with suspected metabolic-associated fatty liver disease (MAFLD) who underwent US-based parameter examinations and liver biopsy were prospectively recruited. The distributions of US parameters across different grades of steatosis were calculated, and diagnostic performance was determined based on the areas under the receiver operating characteristic curve (AUC).

A total of 73 participants were included, with hepatic steatosis grades S0, S1, S2, and S3 distributed as follows: 13, 20, 27, and 13 respectively. The correlation coefficients for CAP, AC, and HRI ranged from 0.67 to 0.74. AC and HRI showed a strong correlation with steatosis grade. The AUC for CAP and AC in diagnosing steatosis ≥ S1 were significantly higher at 0.99 and 0.98 compared to HRI's value. For diagnosing steatosis ≥ S2, the AUC of CAP (AUC: 0.85) was lower than that of AC (AUC: 0.94), and HRI (AUC: 0.94). Similarly for diagnosing steatosis S3, the AUC of CAP (AUC: 0.68) was lower than that of AC (AUC: 0.88), and HRI (AUC: 0.88).

The AC and HRI values increased with the progression of hepatic steatosis grade, while CAP increased from S0 to S2 but not from S2 to S3. For mild steatosis diagnosis, CAP and AC showed superior diagnostic performance compared to HRI, while AC and HRI were more advantageous in differentiating moderate and severe steatosis.

Steatotic liver disease is the most frequent chronic liver disease worldwide. Ultrasonography (US) is commonly employed for the assessment and diagnosis. Few information is available on the possible use of artificial intelligence (AI) to ameliorate the diagnostic accuracy of ultrasonography.

An AI-based algorithm was developed using a dataset of US images. We prospectively enrolled 134 patients for algorithm validation. Patients underwent abdominal US and Proton Density Fat Fraction MRI scans (MRI-PDFF), assumed as reference technique. The hepatorenal index was manually calculated (HRIM) by 4 operators. An automatic hepatorenal index (HRIA) was obtained by the algorithm. The accuracy of HRIA to discriminate steatosis grades was evaluated by ROC analysis using MRI-PDFF cut-offs.

Overweight was 40 % of subjects (BMI 26.4 kg/cm2). The median HRIA was 1.11 (IQR 0.32) and the average of 4 manually calculated HRIM was 1.08 (IQR 0.26), with a 15 % inter-operator variability. Both HRIA (R = 0.79, P < 0.0001) and HRIM (R = 0.69, P < 0.0001) significantly correlated with liver fat percentage (MRI-PDFF). According to MRI-PDFF, 32 % of enrolled subjects had steatosis. Discrimination capacity by AUC between patient with steatosis and patient without steatosis was better for HRIA than HRIM (AUC: 0.87 vs. 0.82, respectively). ROC analysis showed an AUC = 0.98 for HRIA with 1.64 cut-off in distinguishing between mild and moderate/severe groups.

The use of AI improves accuracy and speed of ultrasonography in the diagnosis of liver steatosis. Further studies should evaluate the routine use of this technique in the management of liver steatosis at high cardio-metabolic risk.

The development of steatotic liver disease after liver transplant (LT) is widely described, and epidemiological data have revealed an increased incidence in recent times. Its evolution runs from simple steatosis to steatohepatitis and, in a small proportion of patients, to significant fibrosis and cirrhosis. Apparently, post-LT steatotic disease has no impact on the recipient's overall survival; however, a higher cardiovascular and malignancy burden has been reported. Many donors' and recipients' risk factors have been associated with this occurrence, although the recipient-related ones seem of greater impact. Particularly, pre- and post-LT metabolic alterations are strictly associated with steatotic graft disease, sharing common pathophysiologic mechanisms that converge on insulin resistance. Other relevant risk factors include genetic variants, sex, age, baseline liver diseases, and immunosuppressive drugs. Diagnostic evaluation relies on liver biopsy, although non-invasive methods are being increasingly used to detect and monitor both steatosis and fibrosis stages. Management requires a multifaceted approach focusing on lifestyle modifications, the optimization of immunosuppressive therapy, and the management of metabolic complications. This review aims to synthesize the current knowledge of post-LT steatotic liver disease, focusing on the recent definition of metabolic-dysfunction-associated steatotic liver disease (MASLD) and its metabolic and multisystemic concerns.

MAFLD has become a major global health problem and is the leading cause of liver disease worldwide. The disease progresses from a simple fatty liver to gradual fibrosis, which progresses to cirrhosis and even hepatocellular liver cancer. However, the methods currently used for diagnosis are invasive and do not facilitate clinical assessment of the condition. As a result, research on markers for the diagnosis of MAFLD is increasing. In addition, there are no clinical medications for the treatment of MAFLD, and lifestyle interventions remain effective in the prevention and treatment of MAFLD. In this review, we attempt to make a summary of the emerging diagnostic indicators and effective lifestyle interventions for MAFLD and to provide new insights into the diagnosis and treatment of MAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed non-alcoholic fatty liver disease (NAFLD), is defined as steatotic liver disease (SLD) in the presence of one or more cardiometabolic risk factor(s) and the absence of harmful alcohol intake. The spectrum of MASLD includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH, previously NASH), fibrosis, cirrhosis and MASH-related hepatocellular carcinoma (HCC). This joint EASL-EASD-EASO guideline provides an update on definitions, prevention, screening, diagnosis and treatment for MASLD. Case-finding strategies for MASLD with liver fibrosis, using non-invasive tests, should be applied in individuals with cardiometabolic risk factors, abnormal liver enzymes, and/or radiological signs of hepatic steatosis, particularly in the presence of type 2 diabetes (T2D) or obesity with additional metabolic risk factor(s). A stepwise approach using blood-based scores (such as FIB-4) and, sequentially, imaging techniques (such as transient elastography) is suitable to rule-out/in advanced fibrosis, which is predictive of liver-related outcomes. In adults with MASLD, lifestyle modification - including weight loss, dietary changes, physical exercise and discouraging alcohol consumption - as well as optimal management of comorbidities - including use of incretin-based therapies (e.g. semaglutide, tirzepatide) for T2D or obesity, if indicated - is advised. Bariatric surgery is also an option in individuals with MASLD and obesity. If locally approved and dependent on the label, adults with non-cirrhotic MASH and significant liver fibrosis (stage ≥2) should be considered for a MASH-targeted treatment with resmetirom, which demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile. No MASH-targeted pharmacotherapy can currently be recommended for the cirrhotic stage. Management of MASH-related cirrhosis includes adaptations of metabolic drugs, nutritional counselling, surveillance for portal hypertension and HCC, as well as liver transplantation in decompensated cirrhosis.

Abnormal phospholipid metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD) development and progression. We aimed to clarify whether genetic variants of phospholipid metabolism modify these relationships.

This case-control study consecutively recruited 600 patients who underwent MRI-based proton density fat fraction examination (240 participants with serum metabonomics analysis, 128 biopsy-proven cases) as 3 groups: healthy control, nonobese MASLD, and obese MASLD, (n = 200 cases each). Ten variants of phospholipid metabolism-related genes [phospholipase A2 Group VII rs1805018, rs76863441, rs1421378, and rs1051931; phospholipase A2 receptor 1 (PLA2R1) rs35771982, rs3828323, and rs3749117; paraoxonase-1 rs662 and rs854560; and ceramide synthase 4 (CERS4) rs17160348)] were genotyped using SNaPshot.

The T-allele of CERS4 rs17160348 was associated with a higher risk of both obese and nonobese MASLD (OR: 1.95, 95% CI: 1.20-3.15; OR: 1.76, 95% CI: 1.08-2.86, respectively). PLA2R1 rs35771982-allele is a risk factor for nonobese MASLD (OR: 1.66, 95% CI: 1.11-1.24), moderate-to-severe steatosis (OR: 3.24, 95% CI: 1.96-6.22), and steatohepatitis (OR: 2.61, 95% CI: 1.15-3.87), while the paraoxonase-1 rs854560 T-allele (OR: 0.50, 95% CI: 0.26-0.97) and PLA2R1 rs3749117 C-allele (OR: 1.70, 95% CI: 1.14-2.52) are closely related to obese MASLD. After adjusting for sphingomyelin level, the effect of the PLA2R1 rs35771982CC allele on MASLD was attenuated. Furthermore, similar effects on the association between the CERS4 rs17160348 C allele and MASLD were observed for phosphatidylcholine, phosphatidic acid, sphingomyelin, and phosphatidylinositol.

The mutations in PLA2R1 rs35771982 and CERS4 rs17160348 presented detrimental impact on the risk of occurrence and disease severity in nonobese MASLD through altered phospholipid metabolism.