Search Results (85)

Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, demonstrates robust efficacy in glycemic control and weight reduction. However, substantial interindividual variability in treatment response is observed in clinical practice. In this narrative review, we summarize current evidence on clinical, genetic, and molecular predictors of tirzepatide response and discuss their implications for a precision medicine framework. Data from pivotal clinical trials, post hoc analyses, and relevant preclinical and clinical studies were evaluated to identify determinants of glycemic and weight loss responses, as well as hepatic and renal protective effects. Key clinical predictors include tirzepatide dose, duration of diabetes, β-cell function, baseline glycated hemoglobin, sex, age, race, concomitant therapies, and early treatment response. Genetic factors implicated in treatment variability include variants in GLP-1 receptor, GIP receptor, β-arrestin 1, transcription factor 7-like 2, fat mass and obesity-associated protein, and melanocortin 4 receptor, although tirzepatide-specific validation remains limited. Molecular biomarkers such as branched-chain amino acids, insulin-like growth factor–binding protein-1 and -2, the adiponectin-to-leptin ratio, high-sensitivity C-reactive protein, and interleukin-6 show potential as pharmacodynamic indicators of metabolic response. For organ-specific outcomes, procollagen type III N-terminal peptide and magnetic resonance imaging–proton density fat fraction are supported for assessing hepatoprotective effects, while cystatin C–based estimated glomerular filtration rate and urine albumin-to-creatinine ratio are validated markers of renoprotection. Additional candidates—including tumor necrosis factor receptor 1/2, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin—are promising but require prospective validation. Overall, predicting response to tirzepatide’s multifaceted therapeutic effects necessitates an integrated, multidimensional approach that incorporates clinical characteristics, genetic variation, and molecular profiling. Ongoing validation and harmonization of these predictors may help establish a precision medicine framework for optimizing tirzepatide therapy. Full article

Background: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased rapidly in pediatric populations. Evidence on the cost-effectiveness of pediatric MASLD screening strategies remains limited. Methods: A decision tree combined with a Markov state-transition model was developed to evaluate the cost-effectiveness of three WHtR-based two-stage screening strategies among children aged 6–14 years in Beijing, China: WHtR combined with ultrasound (S1), WHtR combined with FibroScan^® (S2), and WHtR combined with magnetic resonance imaging-proton density fat fraction (MRI-PDFF) (S3), compared with no screening (S4). All screening strategies were combined with lifestyle modification programs, including dietary and exercise management. Model inputs were derived from the published literature, national survey data, and expert consensus. Costs and quality-adjusted life years (QALYs) were estimated from a healthcare system perspective over a 10-year time horizon, with a 3% annual discount rate. Incremental cost–utility ratios (ICURs) were calculated, and extensive one-way, two-way, and probabilistic sensitivity analyses were performed. Results: Our model indicated that, at a willingness-to-pay (WTP) threshold of $30,584.0 per QALY, corresponding to three times the gross domestic product (GDP) per capita of China, S2 was identified as the optimal strategy. At a higher WTP threshold of $71,415.5 per QALY, based on the GDP per capita of Beijing, S3 became the most cost-effective option. All three screening strategies were more cost-effective than no screening across both thresholds. Sensitivity analyses demonstrated that utility values for fibrosis stages and the response rate of the lifestyle modification program were the most influential parameters, and probabilistic sensitivity analysis confirmed the robustness of the baseline findings. Conclusions: To the best of our knowledge, this is the first cost-effectiveness analysis for pediatric MASLD in China. Model-based estimates suggest that early screening for MASLD in children using WHtR-based screening strategies is cost-effective, with FibroScan^® preferred in settings with average economic development and MRI-PDFF preferred in more affluent regions. These findings underscore the importance of context-specific implementation of early MASLD screening strategies in pediatric populations to mitigate long-term disease burden. Full article

Objectives: We aimed to develop models capable of converting the attenuation coefficient (AC) into a percentage-like index in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: In this retrospective, cross-sectional study, we consecutively enrolled participants with suspected MASLD from the Weight Loss Medical Centre who had undergone both ultrasound examinations that yielded AC results and magnetic resonance imaging (MRI) scans including proton density fat fraction (PDFF). The first model, defined as the PDFF conversion fraction (PCF), used the MRI-PDFF results as the reference standard. The other model, defined as the attenuation level fraction (ALF), converted AC values into percentages based on the range of AC values from 0.5 to 1.0 dB/cm/MHz. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the diagnostic performance of the two models. Results: Among the 199 participants (mean age, 38.12 ± 9.56 years; 110 male), the PDFF values differed significantly among the different liver segments (p < 0.05). The PDFF values of the left liver and right liver were 12.6% and 16.1%, respectively. There was a significant difference between them (p < 0.05). The AUCs of the AC, PCF, and ALF were 0.92, 0.93, and 0.87, respectively, for detecting mild steatosis (≥ S1), moderate steatosis (≥S2), and severe steatosis (≥S3) when PDFF values ≥ 5%, ≥15%, and ≥25% were used as the reference standard, respectively. Conclusions: The two fraction conversion models (PCF and ALF) yielded good and identical diagnostic accuracies in grading liver steatosis. Considering the heterogeneous pattern of liver steatosis, the ALF was a more objective parameter. Full article

Background/Objectives: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a global health crisis, but current diagnostics are limited. Liver biopsy is invasive, magnetic resonance imaging-proton density fat fraction (MRI-PDFF) is expensive, and quantitative ultrasound methods are low-accuracy, especially in patients with a high body mass index (BMI). This study introduces a novel thermo-acoustic (TA) method that generates ultrasound signals based on tissue electrical conductivity, where lean tissue (high in water and electrolytes) absorbs more radio-frequency (RF) energy than fatty tissue, providing a direct molecular contrast for fat. Methods: A prospective, cross-sectional feasibility study compared a new thermo-acoustic fat fraction (TAFF) score with the reference standard MRI-PDFF in 40 subjects with suspected fatty liver disease. Bland–Altman analysis, Deming regression, and Binary classification performance were tested. To establish system stability, a dedicated Repeatability and Reproducibility (R&R) study (N = 14) evaluated inter-operator and intra-operator consistency using an Intraclass Correlation Coefficient (ICC) derived from a two-way random-effects ANOVA model. Results: TAFF estimates demonstrated a substantial correlation (r = 0.89) with MRI-PDFF and an average absolute error of 3.04% fat fraction. Classification performance was high, with an Area Under the Receiver Operating Characteristic Curve (AUROC) of 0.92 at the 12% fat fraction threshold and 0.99 at the 20% fat fraction threshold. The R&R study confirmed robust stability (intraclass correlation = 0.89) and a negligible mean inter-operator difference of 0.36%. Estimation errors showed no statistically significant correlation with BMI or other body habitus measurements. Conclusions: These findings support thermoacoustics’ potential as an accurate, non-invasive, point-of-care solution that can serve as a new imaging biomarker. By providing predictive values closely aligned with MRI-PDFF across the full MASLD spectrum, TAFF can complement currently available ultrasound methods to address the cost and access constraints of MRI for the assessment, diagnosis, and monitoring of MASLD. Full article

Background & Aims: The accurate, noninvasive assessment of hepatic steatosis is essential in living liver donor evaluation, where disease prevalence is low, and donor safety is paramount. This study evaluated commonly used noninvasive diagnostic tools for detecting hepatic steatosis in a real-world donor screening setting. Methods: We analyzed 108 living liver donor candidates (18–53 years) with complete MRI, CT, transient elastography (FibroScan^®), and biochemical data obtained during routine donor evaluation. Hepatic steatosis was defined as an MRI-proton density fat fraction (PDFF) ≥5%, which served as the noninvasive reference standard. Diagnostic performance metrics, receiver operating characteristic (ROC) analyses, and correlations with serum fibrosis indices (FIB-4 and APRI) were assessed. Results: MRI-PDFF identified hepatic steatosis in 21 donors (19.4%). Controlled attenuation parameter (CAP), measured by transient elastography, demonstrated high sensitivity (90.5%) and negative predictive value (97.1%), supporting its role as a rule-out screening tool. CT showed excellent specificity (97.7%) but lower sensitivity (61.9%), consistent with a confirmatory role when MRI is unavailable. Serum fibrosis indices were generally low and did not correlate strongly with imaging-based steatosis. Conclusions: In the low-prevalence setting of living liver donor evaluation, CAP-based transient elastography provides effective noninvasive screening for hepatic steatosis, while MRI-PDFF serves as a confirmatory reference when indicated. These findings support a stepwise, clinically practical diagnostic approach that prioritizes donor safety and workflow efficiency. Full article

Background/Objectives: To comparatively evaluate the clinical reliability of automated single-location MRI–proton density fat fraction (PDFF), single-voxel magnetic resonance spectroscopy (MRS), and volumetric MRI-PDFF measurements for quantitative assessment of hepatic steatosis, using manual multi-regions of interest (ROI) MRI-PDFF as the reference standard. Methods: In this retrospective single-center study, adult patients who underwent liver MRI with both MRI-PDFF and MRS between December 2024 and January 2026 were included. Manual multi-ROI MRI-PDFF measurements were obtained from eight Couinaud segments and served as the reference standard. Automated single-location MRI-PDFF, single-voxel MRS, and volumetric MRI-PDFF measurements were extracted from system-generated reports. Fat fraction values and steatosis grades were compared using non-parametric tests, Spearman correlation coefficients, exact agreement rates, weighted Cohen’s kappa statistics, and Bland–Altman analysis. Intra- and inter-observer reliability of manual multi-ROI measurements was assessed using intraclass correlation coefficients (ICC). Results: A total of 490 patients were included. Single-location MRI-PDFF and single-voxel MRS demonstrated high exact agreement with manual multi-ROI MRI-PDFF in steatosis grading (86.9% and 87.4%, respectively), with near-perfect agreement (weighted κ = 0.82–0.83). Volumetric MRI-PDFF showed lower exact agreement (76.1%) and a systematic tendency toward overestimation, with more frequent upward shifts in steatosis grade. All techniques showed strong correlations with manual measurements (ρ = 0.72–0.75). Manual multi-ROI MRI-PDFF demonstrated excellent inter- and intra-observer reliability (ICC > 0.97). Conclusions: Automated single-ROI MRI-PDFF and single-voxel MRS provide clinically reliable and time-efficient alternatives for hepatic steatosis assessment, while automated volumetric MRI-PDFF may introduce systematic bias toward overestimation. Full article

Background/Objectives: The attenuation coefficient (AC) is a quantitative ultrasound parameter that describes the frequency-dependent reduction of acoustic energy as ultrasound waves propagate through biological tissues. Recently, AC has gained increasing relevance in abdominal ultrasound as an objective and reproducible biomarker for tissue characterization, particularly in the assessment of diffuse parenchymal diseases. Unlike conventional qualitative B-mode imaging, AC provides standardized numerical measurements that improve interobserver reproducibility and facilitate longitudinal monitoring. Methods: This review provides a comprehensive and critical overview of the current clinical applications of AC measurements in abdominal ultrasound, mainly focusing on liver steatosis quantification. Emphasis is placed on the comparative evaluation of commercially available AC-based technologies, highlighting their methodological differences, validation evidence, and diagnostic performance to support future efforts toward harmonization and standardization across ultrasound platforms. Results: Several studies have demonstrated a strong correlation between AC values and established reference standards, including magnetic resonance imaging–proton density fat fraction (MRI-PDFF) and histopathological grading, supporting its role in the noninvasive evaluation of liver steatosis. The growing clinical adoption of AC has been accompanied by the development of multiple vendor-specific software implementations integrated into modern ultrasound systems. Although these platforms share a common physical basis, they differ substantially in algorithmic design, signal processing strategies and region-of-interest selection. These differences may influence absolute AC values and diagnostic cutoff thresholds, therefore limiting direct comparability across systems. Another factor that further contributes to the heterogeneity of reported cutoff values is the variability in validation approaches, with some technologies validated against liver biopsy and others against MRI-PDFF. Conclusions: AC is a promising quantitative ultrasound biomarker for noninvasive liver steatosis assessment, showing strong correlation with histology and MRI-PDFF. However, inter-vendor variability currently limits cross-platform comparability. Standardized acquisition protocols, unified quality-control criteria, phantom-based cross-calibration, and consistent vendor-specific reporting are essential to ensure reliable longitudinal monitoring and broader clinical implementation. Full article

Background: Sarcopenia is a clinically important complication of chronic liver disease (CLD), but its underlying mechanisms may differ according to disease etiology. Quantitative MRI biomarkers, including proton density fat fraction (PDFF) and magnetic resonance elastography (MRE), may help characterize etiology-specific patterns of muscle loss. This study aimed to explore etiology-specific associations between MRI-derived biomarkers and sarcopenia, with a particular focus on metabolic dysfunction-associated steatohepatitis (MASH) and viral hepatitis. Methods: This retrospective single-center study included 131 CLD patients (77 with MASH, 54 with viral hepatitis) who underwent MRI, including PDFF and MRE. Sarcopenia was defined by L2 skeletal muscle index thresholds (<42 cm²/m² for men, <38 cm²/m² for women). Muscle identification was performed by automatic threshold-based segmentation by a single observer. Multivariable logistic regression analyses incorporating interaction terms were performed to evaluate whether associations between MRI biomarkers and sarcopenia differed by etiology. Results: Sarcopenia was present in 56% of patients. In the overall cohort, older age (OR = 1.05, p = 0.01), lower PDFF (OR = 0.93, p = 0.03), and lower liver stiffness (OR = 0.51, p = 0.006) were independently associated with sarcopenia. A significant interaction between BMI and disease etiology was observed (p = 0.02). Subgroup analyses suggested that in MASH, sarcopenia was associated with aging, hepatic fat depletion, and lower stiffness. In contrast, in viral hepatitis, it tended to be associated with higher stiffness and lower BMI. Conclusions: MRI-derived hepatic fat and stiffness reflect distinct etiologic patterns of sarcopenia in CLD—metabolically depleted in MASH and fibrosis-related in viral hepatitis. These findings suggest that sarcopenia in MASH and viral hepatitis may reflect different underlying phenotypic patterns, highlighting the importance of considering disease etiology in imaging-based sarcopenia assessment. The results should be interpreted as hypothesis-generating and warrant validation in prospective studies. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging–proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria–endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative–inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances. Full article

Objective: The aim of this study was to evaluate the consistency and reproducibility of attenuation coefficient (AC) measurements using different commercial ultrasound (US) across via a phantom experiment to investigate the relationship between the AC and MRI-derived proton density fat fraction (MRI-PDFF) values and the conversion equation. Methods: Twelve phantoms containing varying fat proportions (0–100%) were constructed. Phantom ACs were estimated via three US attenuation systems, including attenuation imaging (ATI), ultrasound attenuation analysis (USAT), and the US-guided attenuation parameter (UGAP), along with MRI-PDFF. Agreement among the AC values from the three ultrasonic attenuation systems was evaluated. Linear correlation analysis was used to explore the ACs, fat concentrations of the phantom, and MRI-PDFF measurements, from which a linear conversion formula between the ultrasonic attenuation parameters and the MRI-PDFF was derived. Results: MRI-PDFF and phantom fat concentration measurements appeared with a strong linear correlation (R² = 0.996, p < 0.001). For the three US attenuation parameters, both inter-operator and intra-operator intraclass correlation coefficients (ICCs) ranged from 0.990 to 0.995 and 0.989 to 0.995, respectively. Bland–Altman analysis revealed no significant differences between the above three (all p > 0.05). Significant linear relationships were demonstrated between ultrasound attenuation parameters and phantom fat concentration (r = 0.938–0.986; all p < 0.001), as well as between ultrasound attenuation parameters and MRI-PDFF values (r = 0.922–0.982; all p < 0.001). A conversion formula (fat proportions ≤ 50%) was derived: US (dB/cm/MHz) = 0.501 + 0.012 MRI-PDFF (%). Conclusions: AC across different commercial ultrasound devices demonstrated significant diagnostic value in fat concentrations that appeared good consistency in measuring phantom fat concentration both between and within groups. The linear relationship between AC and MRI-PDFF enables the application of a conversion formula. Full article

Background: The current definition of metabolic dysfunction-associated steatotic liver disease (MASLD) relies on a classical assessment of steatosis via liver biopsy, with grades S0–S3 (5–100% fat) potentially underestimating low-grade steatosis. We propose a new, more sensitive classification based on magnetic resonance imaging–proton-density fat fraction (MRI-PDFF), splitting the existing S0 and S1 grades into three classes: new-S0, very early S1 (S1A), and later S1 (S1B). We aimed to determine whether these early S1A/S1B phenotypes differed clinically or biologically from the new-S0 grade using large population cohorts. Methods: We assessed the prevalence of the new MRI-PDFF—based grades in 29,252 healthy participants from the UK Biobank discovery cohort, 286 outpatients with type 2 diabetes, and in six previously published databases (N = 149,212) using SteatoTest-2 or a proxy. We performed a multimodal assessment of steatosis using longitudinal MRI-PDFF and liver biopsy data (N = 286). Models were used to adjust for phenotypes and overall mortality, controlling for age, sex, and cardiometabolic factors. Results: In the UK Biobank cohort, the prevalences of the new-S0, S1A, and S1B grades were 54%, 26%, and 17%, respectively. Grades S1A and new-S0 were most discriminated by triglycerides (odds ratio [OR]: 2.40, 95% confidence interval [CI]: 2.07–2.77, p < 0.00001) and body mass index (BMI; OR: 1.30, 95% CI: 1.27–1.33, p < 0.00001), and grades S1A and S1B were most discriminated by triglycerides, BMI, systolic blood pressure (SBP), and glycated hemoglobin (HbA1c). Adjusting for age, sex, SBP, BMI, HbA1c, triglycerides, and high-density lipoprotein–cholesterol) revealed significantly lower 15-year survival in the high-risk group (97.2%, 95% CI: 96.9–97.7) versus the low-risk (99.4%, 95% CI: 99.2–99.6) group (p < 0.00001). Conclusions: The early trajectory of liver steatosis is undetectable in 26% of middle-aged adults. This early steatosis phenotype differs clinically and biologically from the new-S0 grade in large population cohorts. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing in both prevalence and severity, highlighting the need for non-invasive biomarkers to assess disease activity. Extracellular vesicles (EVs), which carry molecular cargo from their cells of origin, hold promise as accessible biomarkers. We performed proteomic profiling of plasma-derived EVs from 70 patients with MASLD to identify protein signatures associated with key histological features (steatosis, metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis). These proteins were subsequently correlated with magnetic resonance (MR)-based liver imaging. Plasma EV protein profile differed between mild (S1) and advanced steatosis (S3). H4C1, OIT3, and ANPEP were elevated in S3, while CCDC25 and KLHL41 were decreased (|log₂ fold change| > 1, p < 0.05). KLHL41 had a weak-to-moderate correlation with proton density fat fraction (PDFF) (R = −0.34, p = 0.016). GP1BA was upregulated in MASH (log₂ fold change = 1.13, p = 0.03) but showed weak correlation with cT1, an imaging parameter for steatohepatitis (R = 0.22, p = 0.173). In fibrosis, complement component 7 (C7) was elevated in advanced (≥F3) vs. mild fibrosis (<F2) (log₂ fold change = 0.95, adjusted p = 0.002) and correlated with MR elastography-derived liver stiffness (R = 0.38, p = 0.004). The AUC of C7 for differentiating <F2 vs. ≥F2 and <F3 vs. ≥F3 was 0.80 (95% CI: 0.69–0.91) and 0.83 (95% CI: 0.72–0.93), respectively. In conclusion, plasma EVs contain distinct protein signatures associated with steatosis, steatohepatitis, and fibrosis in MASLD. These preliminary findings support the potential utility of plasma EVs as non-invasive biomarkers and provide insights into disease pathophysiology. However, further validation in larger, independent cohorts is necessary to confirm these associations and establish their clinical relevance. Full article

Background: Adolescents suffering from obesity are at higher risk of bone fragility due to hepatic steatosis, which may lead to an inflammatory microenvironment in the bone marrow. We therefore aimed to assess the reliability of measuring the bone marrow fat fraction (BMFF) and T2* of the lumbar vertebral marrow using the proton density fat fraction (PDFF) sequence for adolescents with obesity and liver steatosis. Method: This was an observational feasibility pilot study on adolescents living with obesity and liver steatosis. Anthropometric measurements were obtained. Participants underwent abdominal MRI, MR elastography and dual-energy X-ray absorptiometry (DXA). Regions of interest were drawn using the radiology interface from the central L1 to L4 vertebrae on fat and T2* maps from the PDFF sequence. ImageJ was used to measure abdominal compartment fat areas. Descriptive analyses, the intraclass correlation coefficient, and correlation results were obtained from anthropometric, adiposity, BMFF, and T2* measurements. Results: We recruited 23 adolescents with a body mass index > 85th percentile and mean age = 14.7 years (interval 12–17 years), and n = 18 (78%) were boys. BMFF and T2* measurements were successful in 100% of cases. The intra-operator reproducibility of the BMFF and T2* measurements was excellent: ICC = 0.99 (95% confidence interval (CI) [0.986; 0.999]) and ICC = 0.99 (95% CI [0.992; 0.999]), respectively. The inter-operator ICC was good for BMFF (ICC = 0.89; 95% CI [0.705; 0.963]) and moderate for T2* (ICC = 0.66; 95% CI [0.239; 0.873]). Only BMFF was inversely correlated with vertebral-bone mineral density (r = −0.67; p = 0.0009). However, T2* measurements showed a positive linear relationship with the total body fat tissue percentage measured by DXA (r = 0.48; p = 0.03) and the total abdominal fat area (r = 0.45; p = 0.04). Conclusions: PDFF could be a reliable imaging biomarker for bone health assessment in adolescents living with obesity. Full article

Background/Objectives: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, requiring accurate and accessible diagnostic tools. Methods: A systematic review evaluated the diagnostic performance of Ultrasound-Derived Fat Fraction (UDFF), with a primary focus on prospective studies comparing UDFF to MRI Proton Density Fat Fraction (MRI-PDFF) as the reference standard and a secondary appraisal of its performance against other modalities. Additional parameters, such as technical feasibility, inter-observer agreement, and proposed thresholds, were summarized to support clinical applicability. Results: Seven prospective MRI-based studies (n = 862) demonstrated excellent correlation (average r = 0.848) and reproducibility (inter-observer intraclass correlation coefficient ICC = 0.978, intra-observer ICC = 0.980) of UDFF, with high diagnostic accuracy across steatosis grades (AUCs ≥ 0.89). Additional studies comparing UDFF with Controlled Attenuation Parameter (CAP), histology, and other quantitative ultrasound techniques (attenuation- or backscatter-based methods) confirmed high sensitivity and specificity, particularly for advanced steatosis, and emphasized the potential of UDFF as a comprehensive quantitative biomarker. Proposed UDFF cut-offs for mild, moderate, and severe steatosis ranged from 5% to 23%, demonstrating high sensitivity and specificity. Factors like body position, probe pressure, and visceral fat influenced measurements, underscoring the need for standardized protocols. Conclusions: UDFF seems to offer a reliable and cost-effective quantitative ultrasound modality. So far, it correlates strongly with MRI-PDFF and accurately grades steatosis, especially for S2–S3. Given cut-off variability and protocol sensitivity, broad routine adoption may be premature. Therefore, we recommend further studies focusing on standardized acquisition and cut-off calibration to MRI-PDFF. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as the leading cause of chronic liver disease, closely tied to rising global obesity rates. Endoscopic bariatric therapies (EBTs), including endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), duodenal-jejunal bypass liners (DJBL), and duodenal mucosal resurfacing (DMR), offer minimally invasive interventions that target metabolic dysfunction and weight loss. This review synthesizes current evidence on the mechanisms and hepatic outcomes of EBTs in MASLD, highlighting improvements in hepatic steatosis, liver stiffness, and fibrosis biomarkers across multiple modalities. ESG is consistently associated with reductions in hepatic steatosis and fibrosis scores across multiple studies. IGB therapy improves liver stiffness and reduces hepatic fat as assessed by imaging modalities such as MRI- Proton Density Fat Fraction and ultrasound. DJBL lowers liver enzymes and improves non-invasive markers of steatohepatitis like the Fibroscan-AST score, although its effect on fibrosis appears limited. DMR demonstrates reductions in liver fat, particularly in patients with type 2 diabetes, but evidence for histological improvement in MASLD remains inconsistent. Despite their promise, most EBT studies remain limited by small sample sizes and short follow-up. Further randomized trials are needed to validate long-term efficacy and position EBTs alongside or as alternatives to surgical interventions for MASLD. Full article