This study aimed to explore the association between dietary fiber intake and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD), as well as liver fat content, while considering genetic predispositions of MASLD, gut microbial abundance, and butyrate levels. This study analyzed data from 190,276 participants in the UK Biobank. Dietary fiber intake was assessed using 24-h dietary recall. MASLD cases were diagnosed through hospital admission records and death registries, and liver fat content was measured via magnetic resonance imaging. The genetic predispositions of MASLD, gut microbial abundance, and butyrate levels were evaluated using single nucleotide polymorphisms. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). Over a median follow-up of 10.49 years, 1423 MASLD cases were recorded. Elevated dietary fiber intake was associated with a reduced risk of MASLD (HR: 0.72; 95 % CI: 0.58, 0.90) and a lower level of liver fat content (β: -0.97; 95 % CI: -1.21, -0.73) (all P for trend <0.05). Restricted cubic spline analyses further confirmed the linear inverse associations between fiber intake and the risk of MASLD. Notably, the negative associations between dietary fiber intake and both MASLD and liver fat content were consistent across different genetic predispositions of gut microbial abundance and butyrate levels. Moreover, the inverse association between dietary fiber intake and liver fat was strengthened by high genetic susceptibility of MASLD and elevated body mass index (both P for interaction <0.05). Overall, increased dietary fiber consumption was associated with a lower MASLD risk and decreased liver fat content regardless of genetic predispositions of gut microbial abundance and butyrate levels.

Fatty liver disease (FLD) is a leading cause of chronic liver disease worldwide, yet current diagnostic methods remain limited by low sensitivity, poor accuracy, and prolonged detection times. Recent studies have linked liver viscosity, particularly mitochondrial viscosity variations, to the progression of FLD, highlighting the need for a rapid and noninvasive viscosity-sensitive imaging tool. Herein, we present a viscosity-responsive fluorescent probe ZLCN, designed for rapid real-time imaging of fatty liver disease. ZLCN integrates an acrylonitrile rotor for viscosity sensing and a pyridine moiety for selective mitochondrial localization, enabling precise detection of viscosity alterations at the subcellular level. The probe exhibits strong fluorescence in high-viscosity environments due to restricted intramolecular rotation. ZLCN exhibits excellent viscosity responsiveness, effectively distinguishing normal and cancerous liver cells based on viscosity differences in vitro. Furthermore, it differentiates AML12 cells with varying viscosity levels, demonstrating its capability to monitor viscosity changes. In fatty liver models, ZLCN could produce intense fluorescence signals in fatty liver tissues and enabled rapid viscosity detection within 30 minutes, demonstrating a significant improvement over conventional imaging technique. These findings establish ZLCN as a promising tool for real-time mitochondrial viscosity monitoring, offering new avenues for early diagnosis and therapeutic assessment of viscosity-related liver diseases.

With the increasing need for accurate liver disease diagnostics, non-invasive imaging techniques with rapid and precise quantitative measurements need to be established. This study introduced and validated the application of simultaneous multi-relaxation-time imaging (TXI) for the quantitative assessment of liver tissue by simultaneously acquiring proton density fat fraction (PDFF), lateral relaxation rate (R2*), and longitudinal relaxation time (T1) maps. It aimed to compare the accuracy and consistency of TXI with established quantitative magnetic resonance imaging (MRI) techniques, such as three-dimensional variable flip angle (VFA) T1 mapping, and multi-point quantitative Dixon (qDixon), in healthy volunteers and patients diagnosed with non-alcoholic fatty liver disease (NAFLD).

A prospective cohort of 35 healthy volunteers (mean age: 52±13 years, 21 women) and nine NAFLD patients (mean age: 48±13 years, 6 women) underwent liver MRI using TXI, VFA T1 mapping, and qDixon sequences. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess inter-observer agreement and measurement consistency. Paired T-tests and Pearson correlation coefficients were used to compare the TXI measurements with those from conventional MRI techniques. Differences between the healthy volunteers and NAFLD patients were evaluated using the independent sample T-test.

The ICCs for the TXI-derived T1, R2*, and PDFF in healthy volunteers were 0.985 [95% confidence interval (CI): 0.971-0.993], 0.999 (95% CI: 0.998-1.000), and 0.995 (95% CI: 0.990-0.997), respectively, indicating excellent agreement. The regression analysis revealed strong correlations between the TXI and reference MRI measurements for the T1 (R2=0.895), R2* (R2=0.984), and PDFF (R2=0.894) values with no significant differences (P=0.713, 0.090, and 0.072, respectively). Statistically significant differences were observed in the R2* (P=0.045) and PDFF (P<0.001) values between the NAFLD patients and healthy volunteers, but no significant difference was observed in the T1 values (P=0.965). Multiparametric imaging showed that TXI provides comprehensive liver tissue characterization, consistent with conventional MRI techniques.

TXI offers a rapid and reliable method for the simultaneous acquisition of T1, R2*, and PDFF maps, and has high consistency with established quantitative MRI techniques. This approach has significant potential for non-invasive liver tissue characterization in clinical settings, particularly in the diagnosis and monitoring of conditions such as NAFLD.

Early forms of alcohol-associated liver disease (ALD) include different stages in the progression of compensated liver disease ranging from steatosis to steatohepatitis and fibrosis. ALD has been classically diagnosed at advanced stages more frequently than other liver diseases. This fact probably contributed to the scarcity of studies on early forms of ALD. Recent studies have investigated the prevalence of early ALD in the general population and have described the natural history of alcohol-induced steatosis and fibrosis, which have been linked to worse prognosis compared with early stages of other chronic liver diseases. In addition, studies on screening and early diagnosis of ALD in at-risk populations have shown that these strategies allow early detection and intervention. Of note, up to 28% of the United States population has concurrent alcohol use and metabolic syndrome, and estimated prevalence of advanced fibrosis among heavy drinkers with metabolic syndrome has increased from 3% in the 1990s to more than 10% in the 2010s. Therefore, new challenges and treatment opportunities will emerge for patients with ALD. In this review, we provide an overview of the state of the art in early ALD, focusing on natural history, diagnosis, and management, and provide insights into future perspectives.

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.

To implement, examine the feasibility of, and evaluate the performance of quantitative ultrasound (QUS) with a handheld point-of-care US (POCUS) device for assessing liver fat in adults.

This prospective IRB-approved, HIPAA-compliant pilot study enrolled adults with overweight or obesity. Participants underwent chemical-shift-encoded magnetic resonance imaging to estimate proton density fat fraction (PDFF) and, within 1 mo, QUS with a POCUS device by expert sonographers and novice operators (no prior US scanning experience). Radiofrequency data from the liver collected with the POCUS device were analyzed offline using probe-specific calibrations to estimate two QUS parameters: attenuation coefficient (AC) and backscatter coefficient (BSC). Area under the receiver operating characteristic curve (AUC) of each parameter was estimated for classifying presence/absence of hepatic steatosis (defined as PDFF ≥ 5%). Spearman rank correlation between each parameter and PDFF was estimated and its significance assessed.

Of 18 participants (mean age, 43 y ± 14; 17 women), 8 had hepatic steatosis (PDFF ≥ 5%). Both AC and BSC classified hepatic steatosis accurately with AUCs of 0.96-0.97 for expert and 0.88-0.89 for novice operators (p < 0.01 for all) and correlated significantly with PDFF with rho's of 0.65-0.69 for expert and 0.58-0.65 for novice operators (p < 0.02 for all).

QUS can be implemented on a POCUS device and can be performed by expert or novice operators after limited training in adults with overweight or obesity with promising initial results.

Background and Objectives: Fatty Liver Disease is a major health problem worldwide. We can distinguish liver steatosis as non-associated or associated with chronic/acute alcohol consumption. These two entities share similar stages ranging from hepatic fat storage (namely, steatosis) to inflammation, necrosis, and fibrosis until hepatocellular carcinoma (HCC). Over time, "Metabolic Associated Fatty Liver Disease" (MAFLD) has replaced nonalcoholic fatty liver disease (NAFLD) nomenclature and has included cardiometabolic criteria in these patients definition. Thus, obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia are MAFLD features and are of the metabolic syndrome. Importantly, there is not a specific treatment for MAFLD, but there are therapeutic strategies that act on metabolic dysfunction related to MAFLD. They can reduce the progression of liver fibrosis and its complications. Materials and Methods: For all these reasons, we conducted a narrative review of the literature, and we focused on metabolic dysfunction related to MAFLD, with a special regard for cholesterol metabolism. Results: MAFLD is a recently redefined condition that better describes the metabolism derangement responsible for fatty liver disease. This distinguishes MAFLD from NAFLD. In fact, the diagnostic criteria for MAFLD require the presence of liver steatosis together with at least one of the following: obesity, T2DM, or evidence of metabolic disorder such as hypertriglyceridemia, low high-density lipoprotein cholesterol, or hypertension. As a result, MAFLD is closely linked to an increased cardiometabolic risk. Current therapeutic approaches can be used to reduce this risk, focusing on lifestyle interventions and pharmacological strategies. Several treatments in patients diagnosed with MAFLD are mainly cholesterol-lowering remedies. Among these, Pro-protein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) show the most promising efficacy profile but data on liver fibrosis are lacking. Agonists of GLP-1 receptor, Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and Dipeptidyl Peptidase-4 inhibitors (DPP-4i) have a " multi-hit " action allowing their use also in diabetic patients with MAFLD. Conclusions: Lifestyle modifications, some nutraceuticals, statins, incretins, and PCSK9i have changed the natural course and significantly improved the cardiometabolic outcomes of MAFLD. Emerging cholesterol-lowering drugs, such as Bempedoic acid, can overcome low compliance to statins' use and their controversial effect on liver fibrosis. Finally, medications targeting insulin resistance allow for strategic interventions of the convoluted pathophysiology of MAFLD in multiple steps, with the potential to reduce liver steatosis, inflammation, and necrosis and, sometimes even to reverse liver fibrosis.

We aimed to elucidate the value of ultrasound-based biomarkers for predicting the major life-threatening events in metabolic dysfunction-associated steatotic liver disease (MASLD). We established a prospective cohort of 279 patients who underwent two-dimensional shear wave elastography (2D-SWE), ultrasound-guided attenuation parameter (UGAP). An area under the curve analysis was performed to determine the cutoff values of liver stiffness measurements (LSM) by 2D-SWE and attenuation coefficient (AC) by UGAP for a moderate fibrosis and a moderate steatosis. We then classified the cohort into Groups A (low LSM and low AC), B (low LSM and high AC), C (high LSM and high AC), and D (high LSM and low AC). We compared the incidence of events between the groups, and estimated the hazard ratios (HRs) with 95% confidence intervals (CIs). The LSM and AC cut off values were 8.37 kPa and 0.62 dB/cm/MHz, respectively. The cumulative incidence rate in Groups A, B, C, and D were 11.2%, 12.2%, 29.5%, and 31.0%/5years, respectively (p < 0.05). LSM (HRs = 1.20, 95%CIs: 1.09-1.32, p < 0.01), and AC (HRs = 1.62, 95%CIs: 1.04-2.51, p = 0.03) were associated with life-threatening events. A combination of 2D-SWE and UGAP may help identify patients with MASLD at high risk for subsequent life-threatening events.

The rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has led to an increased occurrence of steatotic liver grafts (SLG) in liver transplantation (LT). However, the implications of SLG on post-transplant de novo hepatic steatosis (PTHS) and advanced fibrosis (≥F3) remain uncertain. This study aimed to characterize PTHS and ≥ F3 using magnetic resonance imaging (MRI) in patients who underwent LT for non-MASLD indications and to examine their relationship with SLG.

Post-LT patients with implant biopsy fat content data were recruited for MRI assessments. MRI-proton density fat fraction (MRI-PDFF) and MR elastography (MRE) were performed using a 1.5 Tesla Optima 450 W MR scanner with a 3D volumetric sequence. PTHS and ≥ F3 were defined as MRI-PDFF ≥5% and MRE ≥3.64 kPa, respectively. SLG was defined as implant biopsy fat content ≥5%.

A total of 292 patients (70.5% men, median age at LT: 51.9 years, 22.6% with SLG) were recruited. The majority (73.6%) were transplanted for hepatitis B virus (HBV)-related complications. MRI performed at a median of 12.2 years post-LT identified PTHS in 27.4 and 10.6% of patients. PTHS was independently associated with SLG (OR 2.067, 95% CI 1.082-3.951), central obesity (OR 3.952, 95% CI 1.768-8.832), and hypertension (OR 2.510, 95% CI 1.268-4.966). In contrast, ≥F3 was associated with sex, change in BMI, and abnormal liver biochemistry but not with PTHS or SLG.

MRI identified a high prevalence of PTHS, which was associated with SLG and metabolic risk factors among Chinese patients transplanted for non-MASLD indications. Advanced graft fibrosis was not associated with PTHS or SLG.

Given the increasing global prevalence of metabolic syndrome, this study aimed to assess the potential of MRI-derived radiomics in noninvasively grading fibrosis. The study included 79 prospectively enrolled participants who had undergone MRE due to known or suspected liver disease between November 2022 and September 2023. Among them, 48 patients were diagnosed with histopathologically confirmed liver fibrosis. A total of 107 radiomic features per patient were extracted from MRI imaging. The dataset was then divided into training and test sets for model development and validation. Stepwise feature reduction was employed to identify the most relevant features and subsequently used to train a gradient-boosted tree model. The gradient-boosted tree model, trained on the training cohort with identified radiomic features to differentiate fibrosis grades, exhibited good performances, achieving AUC values from 0.997 to 0.998. In the independent test cohort of 24 patients, the radiomics model demonstrated AUC values ranging from 0.617 to 0.830, with the highest AUC of 0.830 (95% CI 0.520-0.830) for classifying fibrosis grade 2. Incorporating ADC values did not improve the model's performance. In conclusion, our study emphasizes the significant promise of using radiomics analysis on MRI images for noninvasively staging liver fibrosis. This method provides valuable insights into tissue characteristics and patterns, enabling a retrospective liver fibrosis severity assessment from nondedicated MRI scans.

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.

Determining sentinel lymph node (SLN) status is important for treatment decisions in patients with melanoma. Superparamagnetic iron oxide nanoparticles (SPIO) combined with MRI have emerged as an alternative to Technetium99m lymphoscintigraphy for preoperative mapping of SLN, however, the MRI protocols so far are extensive with long in-camera time. This study aimed to evaluate an optimized MRI protocol for rapid identification of SLNs using SPIO as a tracer, without compromising diagnostic quality, the GOthenburg Fast Acquisition Sentinel lymph node Tracking MRI (GO-FAST-MRI).

In this prospective single-center pilot study, patients with confirmed melanoma on the trunk or limbs, without clinically suspected lymph node metastasis, were eligible. All patients received an injection of 0.1 mL SPIO divided into four quadrants around the scar. The GO-FAST-MRI protocol, using only T1-weighted and Dixon sequences over the axillary or inguinal basins, was conducted no earlier than 30 min post-injection. Technetium and lymphoscintigraphy were used according to routine. SLN-biopsy was performed using a handheld magnetometer and gamma probe for SLN-detection.

Twenty-one patients were enrolled, and SLNs were successfully identified in all with both methods. The GO-FAST-MRI protocol was performed in 4 min and detected more SLNs than lymphoscintigraphy (54 vs 42), but the number of SLNs identified during surgery with the magnetometer and gamma probe was the same (50 for both methods). Of the SLNs removed, five were found to have metastases, all of which showed uptake of SPIO and Tc99m.

The novel GO-FAST-MRI protocol, with a 4-min scan-time, was feasible in detecting SLNs in all patients. Both the preoperative SLN-mapping and intraoperative SLN-detection using the magnetic technique was comparable to the radioactive technique.

Noninvasive tools assessing steatosis, such as ultrasonography-based 2D-attenuation imaging (ATI), are needed to tackle the worldwide burden of steatotic liver disease. This one-stage individual patient data (IPD) meta-analysis aimed to create an ATI-based steatosis grading system.

A systematic review (EMBASE + MEDLINE, 2018-2022) identified studies, including patients with histologically or magnetic resonance imaging proton-density fat fraction (MRI-PDFF)-verified ATI for grading steatosis (S0 to S3). One-stage IPD meta-analyses were conducted using generalized mixed models with a random study-specific intercept. Created ATI-based steatosis grading system (aS0 to aS3) was externally validated on a prospective cohort of patients with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (n=174, histologically and MRI-PDFF-verified steatosis). Eleven enrolled studies included 1374 patients, classified into S0, S1, S2, and S3 in 45.4%, 35.0%, 9.3%, and 10.3% of the cases. ATI was correlated with histological steatosis ( r = 0.60; 95% CI: 0.52, 0.67; p < 0.001) and MRI-PDFF ( r = 0.70; 95% CI: 0.66, 0.73; p < 0.001) but not with liver stiffness ( r = 0.03; 95% CI: -0.04, 0.11, p = 0.343). Steatosis grade was an independent factor associated with ATI (coefficient: 0.24; 95% CI: [0.22, 0.26]; p < 0.001). ATI marginal means within S0, S1, S2, and S3 subpopulations were 0.59 (95% CI: [0.58, 0.61]), 0.69 (95% CI [0.67, 0.71]), 0.78 (95% CI: [0.76, 0.81]), and 0.85 (95% CI: [0.83, 0.88]) dB/cm/MHz; all contrasts between grades were significant ( p < 0.0001). Three ATI thresholds were calibrated to create a new ATI-based steatosis grading system (aS0 to aS3, cutoffs: 0.66, 0.73, and 0.81 dB/cm/MHz). Its external validation showed Obuchowski measures of 0.84 ± 0.02 and 0.82 ± 0.02 with histologically based and MRI-PDFF-based references.

ATI is a reliable, noninvasive marker of steatosis. This validated ATI-based steatosis grading system could be valuable in assessing patients with metabolic dysfunction-associated steatotic liver disease.

To investigate the accuracy of proton density fat fraction (PDFF) measurement using chemical shift-encoded MRI (CSE-MRI) with fast imaging techniques in a phantom.

A 1.5T imaging system (Prodiva; Philips Healthcare) and PDFF phantom (Fat Fraction Phantom Model 300; Calimetrix) were used in this study. The acquisitions without fast imaging techniques (conventional acquisition), with parallel imaging in phase-encode direction (SENSE acquisition), with compressed sensing (CS-SENSE acquisition), and with parallel imaging in both phase-encode and slice-encode direction (Dual-SENSE acquisition) were performed. The following acceleration factors in SENSE and CS-SENSE acquisition were used: 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, and 8.0. For Dual-SENSE acquisition, the same acceleration factors (1.5, 2.0, 3.0, 4.0, 5.0) were set in each of the two directions. The relationships between reference PDFF values and PDFF measurements obtained using each acquisition were assessed using linear regression analysis and Bland-Altman analysis.

According to the linear regression analysis, the slopes and intercepts of regression lines were from 0.87 to 1.02 and from 0.06% to 3.55%, respectively. According to Bland-Altman analysis, there were fixed bias between reference PDFF values and PDFF measurements obtained using SENSE acquisition with reduction factor 8.0 and Dual-SENSE acquisition with reduction factor 5.0. For CS-SENSE acquisition with reduction factor from 7.0 to 8.0, SENSE acquisition with reduction factor from 3.0 to 8.0, and Dual-SENSE acquisition with reduction factor from 2.0 to 5.0, some vials had ±1.5% or more errors between the reference PDFF values and PDFF measurements in the range of 0% to 50% PDFF.

In CS-SENSE acquisition, the accuracy of PDFF measurement was maintained within 1.5% up to a reduction factor 6.0. The accuracy of PDFF measurement was maintained within 1.5% up to a reduction factor 2.0 in SENSE acquisition and a reduction factor 1.5 in Dual-SENSE acquisition.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is currently the most common chronic liver disease worldwide and is strongly associated with metabolic comorbidities, including dyslipidemia.

Herein, we aim to estimate the prevalence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) in Europeans with isolated hypercholesterolemia and isolated hypertriglyceridemia in the UK Biobank and to estimate the independent contribution of lipoproteins to liver triglyceride content.

We selected 218 732 Europeans from the UK Biobank without chronic viral hepatitis and other causes of liver disease, of whom 14 937 with liver magnetic resonance imaging data available. Next, to examine the relationships between traits in predicting liver triglyceride content, we compared the predictive performance of several machine learning methods and selected the best performing algorithms based on the minimum cross-validated mean squared error (MSE).

There was an approximately 3-fold and 4-fold enrichment of MASLD and MASH in individuals with isolated hypertriglyceridemia (P = 1.23 × 10-41 and P = 1.29 × 10-10, respectively), whereas individuals with isolated hypercholesterolemia had a marginal higher rate of MASLD and no difference in MASH rate compared with the control group (P = .019 and P = .97, respectively). Among machine learning methods, the feed-forward neural network had the best cross-validation MSE on the validation set. Circulating triglycerides, after body mass index, were the second strongest independent predictor of liver proton density fat fraction with the largest absolute mean Shapley additive explanation value.

Isolated hypertriglyceridemia is the second strongest, after obesity, independent predictor of MASLD/MASH. Individuals with hypertriglyceridemia, but not with hypercholesterolemia, should be screened for liver disease.

The fatty liver disease represents a complex, multifaceted challenge, requiring a multidisciplinary approach for effective management and research. This article uses conventional and advanced imaging techniques to explore the etiology, imaging patterns, and quantification methods of hepatic steatosis. Particular emphasis is placed on the challenges and advancements in the imaging diagnostics of fatty liver disease. Techniques such as ultrasound, CT, MRI, and elastography are indispensable for providing deep insights into the liver's fat content. These modalities not only distinguish between diffuse and focal steatosis but also help identify accompanying conditions, such as inflammation and fibrosis, which are critical for accurate diagnosis and management.

This study aimed to evaluate the performances of quantitative ultrasound (QUS) for the detection and assessment of hepatic steatosis when implemented using an ultraportable ultrasound scanner.

Seven established QUS parameters were investigated. Ultrasound signals were acquired using a new ultraportable ultrasound device, the Hepatoscope. The feasibility of QUS using the Hepatoscope was first assessed in vitro. Clinical reliability, accuracy and staging capabilities were evaluated in 60 patients referred to a hepatology consultation for known chronic liver disease and enrolled in a prospective clinical investigation using the controlled attenuation parameter (CAP) as ground truth.

QUS parameters showed moderate (intra-class correlation coefficient [ICC] >0.50) to excellent (ICC >0.90) reliability. Two parameters, namely Lizzi-Feleppa mid-band fit and attenuation, were both reliable (ICC = 0.89 and 0.86, respectively) and correlated with the CAP (squared Pearson correlation coefficient of R2 = 0.65 and R2 = 0.6, respectively). For steatosis detection (S0 vs. ≥S1), the two parameters yielded an area under the receiving operating characteristic curve of 0.90 and 0.86, respectively (95% confidence interval: [0.81-0.99] and [0.76-0.96], respectively).

QUS can be reliably and accurately implemented on ultraportable ultrasound scanners. The combination of ultraportability and quantitative assessment of liver fat is promising for large-scale screening and monitoring of hepatic steatosis.

The American Academy of Pediatrics advises that the nutrition of preterm infants should target a body composition similar to that of a fetus in utero. Still, reference charts for intrauterine body composition are missing. Moreover, data on sexual differences in intrauterine body composition during pregnancy are limited.

The objective of this study was to create reference charts for intrauterine body composition from 30 to 36+6 weeks postconception and to evaluate the differences between sexes.

In this single-center retrospective study, data from 197 normal developing fetuses in late gestation was acquired at 3T magnetic resonance imaging (MRI) scans, including True Fast Imaging with Steady State Free Precession and T1-weighted 2-point Dixon sequences covering the entire fetus. Deep convolutional neural networks were utilized to automatically segment the fetal body and subcutaneous adipose tissue. The fetus's body mass (BM), fat signal fraction (FSF), fat mass (FM), FM percentage (FM%), fat-free mass (FFM), and FFM percentage (FFM%) were calculated. Using the Generalized Additive Models for Location, Scale, and Shape (GAMLSS) method, reference charts were created, and sexual dimorphism was examined using analysis of covariance (ANCOVA). A P value <0.05 was deemed significant.

Throughout late gestation, BM, FSF, FM, FM%, and FFM increased, while the FFM% decreased. Reference charts for gestational age and sex-specific percentiles are provided. Males exhibited significantly higher BM (7.2%; 95% confidence interval [95% CI]: 1.9, 12.4), FFM (8.8%; 95% CI: 5.8, 11.9), and FFM% (1.7%; 95% CI: 1, 2.4) and lower FSF (-3.6%; 95% CI: -5.6, -1.8) and FM% (-1.7%; 95% CI: -2.4, -1), (P < 0.001) compared with females, with no significant difference in FM between sexes (P = 0.876).

MRI-derived intrauterine body composition growth charts are valuable for tracking growth in preterm infants. This study demonstrated that sexual differences in body composition are already present in the intrauterine phase.

There is an unmet need for a reliable and reproducible non-invasive measure of fatty liver content (FLC) for monitoring steatotic liver disease in clinical practice. Sonographic FLC assessment is qualitative and operator-dependent, and the dynamic quantification range of algorithms based on a single ultrasound (US) parameter is unsatisfactory. This study aims to develop and validate a new multiparametric algorithm based on B-mode images to quantify FLC using Magnetic Resonance (MR) values as standard reference.

Patients with elevated liver enzymes and/or bright liver at US (N = 195) underwent FLC evaluation by MR and by US. Five US-derived quantitative features [attenuation rate(AR), hepatic renal-ratio(HR), diaphragm visualization(DV), hepatic-portal-vein-ratio(HPV), portal-vein-wall(PVW)] were combined by mixed linear/exponential regression in a multiparametric model (Steatoscore2.0). One hundred and thirty-four subjects were used for training and 61 for independent validations; score-computation underwent an inter-operator reproducibility analysis.

The model is based on a mixed linear/exponential combination of 3 US parameters (AR, HR, DV), modelled by 2 equations according to AR values. The computation of FLC by Steatoscore2.0 (mean ± std, 7.91% ± 8.69) and MR (mean ± std, 8.10% ± 10.31) is highly correlated with a low root mean square error in both training/validation cohorts, respectively (R = 0.92/0.86 and RMSE = 5.15/4.62, p < .001). Steatoscore2.0 identified patients with MR-FLC≥5%/≥10% with sensitivity = 93.2%/89.4%, specificity = 86.1%/95.8%, AUROC = 0.958/0.975, respectively and correlated with MR (R = 0.92) significantly (p < .001) better than CAP (R = 0.73).

Multiparametric Steatoscore2.0 measures FLC providing values highly comparable with MR. It is reliable, inexpensive, easy to use with any US equipment and qualifies to be tested in larger, prospective studies as new tool for the non-invasive screening and monitoring of FLC.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously termed nonalcoholic fatty liver disease, is a major global health issue and a leading cause of chronic liver disease. The prevalence of MASLD is increasing globally, with the disease in some patients progressing to metabolic dysfunction-associated steatohepatitis (MASH), which significantly raises the risk of fibrosis, cirrhosis, and adverse outcomes. Accurate identification of patients with at-risk MASH, defined as MASH with a fibrosis stage of 2 or higher, is critical for timely intervention and management. Although liver biopsy remains the gold standard for diagnosing MASH, its invasive nature, potential complications, and variability in interpretation necessitate the implementation of noninvasive tests (NITs). NITs hold the potential for reducing reliance on liver biopsies, enhancing early diagnosis, and improving patient management of chronic liver disease. Continued research and validation are essential to optimize these tools for clinical application. This article explores current NITs, including imaging biomarkers, combined imaging and serum biomarkers, advanced biomarkers and composite scores, as well as artificial intelligence-based approaches, which also show promise in improving the accuracy of noninvasive at-risk MASH detection.

Chronic liver diseases (CLDs) have diverse etiologies. To better classify CLDs, we explored the ability of longitudinal multiparametric MRI (magnetic resonance imaging) in depicting alterations in liver morphology, inflammation, and hepatocyte and macrophage activity in murine high-fat diet (HFD)- and carbon tetrachloride (CCl 4 )-induced CLD models.

Mice were either untreated, fed an HFD for 24 weeks, or injected with CCl 4 for 8 weeks. Longitudinal multiparametric MRI was performed every 4 weeks using a 7 T MRI scanner, including T1/T2 relaxometry, morphological T1/T2-weighted imaging, and fat-selective imaging. Diffusion-weighted imaging was applied to assess fibrotic remodeling and T1-weighted and T2*-weighted dynamic contrast-enhanced MRI and dynamic susceptibility contrast MRI using gadoxetic acid and ferucarbotran to target hepatocytes and the mononuclear phagocyte system, respectively. Imaging data were associated with histopathological and serological analyses. Principal component analysis and clustering were used to reveal underlying disease patterns.

The MRI parameters significantly correlated with histologically confirmed steatosis, fibrosis, and liver damage, with varying importance. No single MRI parameter exclusively correlated with 1 pathophysiological feature, underscoring the necessity for using parameter patterns. Clustering revealed early-stage, model-specific patterns. Although the HFD model exhibited pronounced liver fat content and fibrosis, the CCl 4 model indicated reduced liver fat content and impaired hepatocyte and macrophage function. In both models, MRI biomarkers of inflammation were elevated.

Multiparametric MRI patterns can be assigned to pathophysiological processes and used for murine CLD classification and progression tracking. These MRI biomarker patterns can directly be explored clinically to improve early CLD detection and differentiation and to refine treatments.

We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus.

This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05).

Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, has a high global prevalence and can progress to metabolic dysfunction-associated steatohepatitis, cirrhosis, and hepatocellular carcinoma. The pathogenesis of MASLD is primarily driven by disturbances in hepatic lipid metabolism, involving six key processes: increased hepatic fatty acid uptake, enhanced fatty acid synthesis, reduced oxidative degradation of fatty acids, increased cholesterol uptake, elevated cholesterol synthesis, and increased bile acid synthesis. Consequently, maintaining hepatic lipid metabolic homeostasis is essential for effective MASLD management. Numerous novel molecules and Chinese proprietary medicines have demonstrated promising therapeutic potential in treating MASLD, primarily by inhibiting lipid synthesis and promoting lipid oxidation. In this review, we summarized recent research on MASLD, elucidated the molecular mechanisms by which lipid metabolism disorders contribute to MASLD pathogenesis, and discussed various lipid metabolism-targeted therapeutic approaches for MASLD.

(1) Background: Ultrasound attenuation imaging (ATI) is an innovative technique that allows for the evaluation of the degree of lipid infiltration of the liver parenchyma in a simple and non-invasive way. The objective of this study was to verify the applicability of the ATI method in the evaluation of hyperlipidemia. (2) Methods: This study included 53 dogs between January 2021 and December 2022, of which 21 were healthy (A) and 32 had hyperlipidemia (B). The dogs of Group B were divided into mild hyperlipidemic (B1; n = 15) and moderate/severe hyperlipidemic (B2; n = 17). Each dog underwent biochemical examination, B-mode ultrasound and ATI investigation at the liver level via a right intercostal approach. (3) Results: The mean AC value was significantly higher in Group B (0.95 ± 0.23 dB/cm/MHz) compared to Group A (0.81 ± 0.10 dB/cm/MHz). No statistically significant differences were highlighted regarding the ATI values between the subjects with mild and moderate/severe hyperlipidemia. (4) Conclusion: ATI could be a promising method for the non-invasive evaluation of hepatic steatosis in veterinary medicine.

Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training.

We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness.

Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight).

Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

International expert panels proposed new nomenclatures, metabolic dysfunction-associated fatty liver disease (MAFLD) in 2020 and metabolic dysfunction-associated steatotic liver disease (MASLD) in 2023, along with revised diagnostic criteria to replace non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the differences in NAFLD, MAFLD, and MASLD prevalence with changing nomenclature in a health check-up using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) to assess hepatic steatosis. We also examined the prevalence of the sub-classifications of steatotic liver disease (SLD) and the differences in characteristics among the sub-categories.

We included 844 participants who underwent liver MRI-PDFF at our health check-up clinic between January 2020 and November 2022. Hepatic steatosis was defined as MRI-PDFF ≥ 5%. Participants were categorized according to NAFLD, MAFLD, MASLD, and sub-classifications of SLD.

The prevalence rates of NAFLD, MAFLD, and MASLD were 25.9%, 29.5%, and 25.2%, respectively. 30.5% of the participants was categorized as SLD. The prevalence rates of the SLD sub-categories were 25.2% for MASLD, 3.7% for MASLD and alcohol-associated liver disease (MetALD), 0.1% for alcohol-associated liver disease, 1.3% for specific etiology SLD, and 0.1% for cryptogenic SLD. Compared with patients in the MASLD group, those in the MetALD group were younger, predominantly male, and exhibited higher levels of serum aspartate aminotransferase, gamma-glutamyl transpeptidase, and triglycerides.

The prevalences of NAFLD and MASLD assessed using MRI-PDFF were similar, with MASLD accounting for 97.3% of the patients with NAFLD. The separate MetALD sub-category may have clinical characteristics that differ from those of MASLD.

Nonalcoholic fatty liver disease (NAFLD) has become a growing public health problem worldwide. However, there is still lack of effective treatment strategies except lifestyle intervention.

To evaluate whether quercetin improves intrahepatic lipid content in patients with NAFLD.

In this randomized, double-blind, placebo-controlled crossover trial, 41 patients with NAFLD were randomly assigned to receive the quercetin (500 mg) or placebo capsules for 12 wk, then switched interventions for another 12 wk after a 4-wk washout period. The primary outcome was intrahepatic lipid content evaluated by magnetic resonance imaging estimated proton density fat fraction. The secondary outcomes were liver function measurements, etc. Safety outcomes included blood routine.

A total of 36 patients completed the trial. In intention-to-treat analyses, the quercetin intervention moderately decreased the intrahepatic lipid contents from 11.5% ± 6.4% to 9.6% ± 5.8%, compared with the placebo intervention (decreased by 0.1% ± 2.6%, P = 0.013 and adjusted P value is 0.028). Body weight and body mass index were mildly reduced by 1.5 ± 2.6 kg and 0.5 ± 0.9 kg/m2 after the quercetin intervention (P < 0.05 and both adjusted P values are 0.038), whereas the reductions were only 0.2 ± 1.8 kg and 0.1 ± 0.7 kg/m2 after the placebo intervention. The intrahepatic lipid content reductions were noticeably positively associated with the body weight losses after the quercetin and placebo interventions (r = 0.557 and 0.412, P < 0.001 and P = 0.007, respectively). Subgroup analyses found that the reduction of intrahepatic lipid contents in females (3.0% ± 3.7%) was about twice as large as that in males (1.4% ± 2.5%) with a trend of statistical significance (P = 0.113 and adjusted P value is 0.061). There were no significant differences in other secondary and safety outcomes. No adverse events associated with study intervention were found.

Twelve weeks treatment of quercetin could reduce intrahepatic lipid contents in patients with NAFLD, possibly explained by a slightly larger body weight loss in the quercetin group.

The trial is registered at www.chictr.org.cn as ChiCTR2100047904.

Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism.

Open-label, 48-week randomized trial with a 2 x 2 factorial design.

Multicenter HIV clinics.

Nondiabetic, virologically suppressed PLWH, aged at least 35 years, with confirmed/suspected MAFLD (≥1 biochemical/anthropometric/radiological/histological features).

Adjunctive MVC; MET; MVC+MET vs. antiretroviral therapy (ART) alone.

Change in liver fat fraction (LFF) between baseline and week-48 using magnetic resonance proton density fat fraction (MR PDFF).

Six sites enrolled 90 participants (93% male; 81% white; median age 52 [interquartile range, IQR 47-57] years) between March 19, 2018, and November 11, 2019. Seventy percent had imaging/biopsy and at least one 1 MAFLD criteria. The analysis included 82/90 with week-0 and week-48 scans. Median baseline MR PDFF was 8.9 (4.6-17.1); 40, 38, 8, and 14% had grade zero, one, two, and three steatosis, respectively. Mean LFF increased slightly between baseline and follow-up scans: 2.22% MVC, 1.26% MET, 0.81% MVC+MET, and 1.39% ART alone. Prolonged intervention exposure (delayed week-48 scans) exhibited greater increases in MR PDFF (estimated difference 4.23% [95% confidence interval, 95% CI 2.97-5.48], P  < 0.001). There were no differences in predicted change for any intervention compared to ART alone: MVC (-0.42% [95% CI -1.53 to 0.68, P  = 0.45]), MET (-0.62 [-1.81 to 0.56, P  = 0.30]), and MVC+MET (-1.04 [-2.74 to 0.65, P  = 0.23]). Steatosis grade remained unchanged in 55% and increased in 24%.

Baseline levels of liver fat were lower than predicted. Contrary to our hypothesis, neither MVC, MET, or the combination significantly reduced liver fat as measured by MRPDFF compared to ART alone.

Genetic variants associated with increased liver fat and volume have been reported, but whether physical activity (PA) can attenuate the impact of genetic susceptibility to these traits is poorly understood. We aimed to investigate whether higher PA modify genetic impact on liver-related traits in the UK Biobank cohort. PA was self-reported, while magnetic resonance images were used to estimate liver fat (n = 27,243) and liver volume (n = 24,752). Metabolic dysfunction-associated liver disease (MASLD) and chronic liver disease (CLD) were diagnosed using ICD-9 and ICD-10 codes. Ten liver fat and eleven liver volume-associated genetic variants were selected and unweighted genetic-risk scores for liver fat (GRSLF) and liver volume (GRSLV) were computed. Linear regression analyses were performed to explore interactions between GRSLF/ GRSLV and PA in relation to liver-related traits. Association between GRSLF and liver fat was not different among lower (β = 0.063, 95% CI 0.041-0.084) versus higher PA individuals (β = 0.065, 95% CI 0.054-0.077, pinteraction = 0.62). The association between the GRSLV and liver volume was not different across different PA groups (pinteraction = 0.71). Similarly, PA did not modify the effect of GRSLF and GRSLV on MASLD or CLD. Our findings show that physical activity and genetic susceptibility to liver-related phenotypes seem to act independently, benefiting all individuals regardless of genetic risk.

The population with metabolic dysfunction-associated fatty liver disease (MAFLD) is increasingly common worldwide. Identification of people at risk of progression to advanced stages is necessary to timely offer interventions and appropriate care. Liver biopsy is currently considered the gold standard for the diagnosis and staging of MAFLD, but it has associated risks and limitations. This has spurred the exploration of non-invasive diagnostics for MAFLD, especially for steatohepatitis and fibrosis. These non-invasive approaches mostly include biomarkers and algorithms derived from anthropometric measurements, serum tests, imaging or stool metagenome profiling. However, they still need rigorous and widespread clinical validation for the diagnostic performance.

Dynamic changes in non-invasive tests, such as changes in alanine aminotransferase (ALT) and MRI proton-density-fat-fraction (MRI-PDFF), may help to detect metabolic dysfunction-associated steatohepatitis (MASH) resolution, but a combination of non-invasive tests may be more accurate than either alone. We developed a novel non-invasive score, the MASH Resolution Index, to detect the histological resolution of MASH.

This study included a derivation cohort of 95 well-characterised adult participants (67% female) with biopsy-confirmed MASH who underwent contemporaneous laboratory testing, MRI-PDFF and liver biopsy at two time points. The primary objective was to develop a non-invasive score to detect MASH resolution with no worsening of fibrosis. The most predictive logistic regression model was selected based on the highest area under the receiver operating curve (AUC), and the lowest Akaike information criterion and Bayesian information criterion. The model was then externally validated in a distinct cohort of 163 participants with MASH from a clinical trial.

The median (IQR) age and body mass index were 55 (45-62) years and 32.0 (30-37) kg/m2, respectively, in the derivation cohort. The most accurate model (MASH Resolution Index) included MRI-PDFF, ALT and aspartate aminotransferase. The index had an AUC of 0.81 (95% CI 0.69 to 0.93) for detecting MASH resolution in the derivation cohort. The score calibrated well and performed robustly in a distinct external validation cohort (AUC 0.83, 95% CI 0.76 to 0.91), and outperformed changes in ALT and MRI-PDFF.

The MASH Resolution Index may be a useful score to non-invasively identify MASH resolution.