Multifrequency MR elastography (mMRE) enables noninvasive quantification of renal stiffness in patients with chronic kidney disease (CKD). Manual segmentation of the kidneys on mMRE is time-consuming and prone to increased interobserver variability.

To evaluate the performance of mMRE combined with automatic segmentation in assessing CKD severity.

Prospective.

A total of 179 participants consisting of 95 healthy volunteers and 84 participants with CKD.

3 T, single shot spin echo planar imaging sequence.

Participants were randomly assigned into training (n = 58), validation (n = 15), and test (n = 106) sets. Test set included 47 healthy volunteers and 58 CKD participants with different stages (21 stage 1-2, 22 stage 3, and 16 stage 4-5) based on estimated glomerular filtration rate (eGFR). Shear wave speed (SWS) values from mMRE was measured using automatic segmentation constructed through the nnU-Net deep-learning network. Standard manual segmentation was created by a radiologist. In the test set, the automatically segmented renal SWS were compared between healthy volunteers and CKD subgroups, with age as a covariate. The association between SWS and eGFR was investigated in participants with CKD.

Dice similarity coefficient (DSC), analysis of covariance, Pearson and Spearman correlation analyses. P < 0.05 was considered statistically significant.

Mean DSCs between standard manual and automatic segmentation were 0.943, 0.901, and 0.970 for the renal cortex, medulla, and parenchyma, respectively. The automatically quantified cortical, medullary, and parenchymal SWS were significantly correlated with eGFR (r = 0.620, 0.605, and 0.640, respectively). Participants with CKD stage 1-2 exhibited significantly lower cortical SWS values compared to healthy volunteers (2.44 ± 0.16 m/second vs. 2.56 ± 0.17 m/second), after adjusting age.

mMRE combined with automatic segmentation revealed abnormal renal stiffness in patients with CKD, even with mild renal impairment.

The renal stiffness of patients with chronic kidney disease varies according to the function and structure of the kidney. This study integrates multifrequency magnetic resonance elastography with automated segmentation technique to assess renal stiffness in patients with chronic kidney disease. The findings indicate that this method is capable of distinguishing between patients with chronic kidney disease, including those with mild renal impairment, while simultaneously reducing the subjectivity and time required for radiologists to analyze images. This research enhances the efficiency of image processing for radiologists and assists nephrologists in detecting early-stage damage in patients with chronic kidney disease.

2 TECHNICAL EFFICACY: Stage 2.

To evaluate the test-retest repeatability of a rapid, free-breathing two-dimensional (2D) MR elastography (MRE) technique and to assess the reliability of the liver-stiffness measurements compared with conventional breath-hold MREs.

Fifteen and 115 participants were enrolled in the technical repeatability and measurement equivalence assessment cohorts, respectively. All participants underwent rapid free-breathing and conventional breath-hold 2D MRE (twice in repeatability cohort) on 1.5T scanners. Both methods have four phase offsets over one harmonic motion cycle at 60 Hz; one and 10 cycles were collected and processed in breath-hold and free-breathing MREs, respectively. The liver stiffness measurements of free-breathing (LSF) and breath-hold MRE (LSB) were calculated from manually drawn regions of interest. The repeatability coefficients and Spearman correlation were used to assess technical repeatability and measurement agreement between LSF and LSB. Univariable and multivariable linear regressions were performed to identify potential influencing factors, including age, sex, body mass index, and fat fraction, in the measurement agreement between LSB and LSF.

The repeatability coefficient of free-breathing 2D MRE is comparable to breath-hold MRE (LSF: 20.8%, LSB: 20.4%). LSF showed a strong agreement and significant correlation with LSB (LSF = 1.01 × LSB, ρ = 0.94, p < 0.001). The measurement agreement between LSF and LSB was only significantly affected by sex (p = 0.047) after adjusting for confounding factors of age, body mass index, and fat fraction.

The nongated, free-breathing, multislice 2D MRE technique can provide reliable liver stiffness measurements compared with conventional breath-hold 2D MRE. It could provide a comfortable alternative method with reliable liver stiffness measurements for patients who have difficulty in suspending respiration.

Tissue viscoelasticity is becoming an increasingly useful biomarker beyond elasticity and can theoretically be estimated using shear wave elastography by inverting the propagation and attenuation characteristics of shear waves. Estimating viscosity is often more difficult than elasticity because attenuation, the main effect of viscosity, leads to poor signal-to-noise ratio of the shear wave motion. In the present work, we provide an alternative to existing methods of viscoelasticity estimation, based on peaks in the frequency-wavenumber (f-k) domain, which are considered more robust against noise compared with other features in the f-k domain. Specifically, the method minimizes the difference between simulated and measured versions of two sets of peaks (twin peaks) in the f-k domain, obtained first by traversing through each frequency and then by traversing through each wavenumber. The slopes and deviation of the twin peaks are sensitive to elasticity and viscosity, respectively, leading to the effectiveness of the proposed inversion algorithm for characterizing mechanical properties. This expected effectiveness is confirmed through in silico verification, followed by ex vivo validation and in vivo application, indicating that the proposed approach can be used effectively in accurately estimating viscoelasticity, thus potentially contributing to the development of enhanced biomarkers.

This prospective study aimed to compare the diagnostic performance of 2D-shear wave elastography (2D-SWE) with vibration-controlled transient elastography (VCTE) for assessing liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

Ninety-one participants (mean age: 42±13 years; 52 males) suspected of MASLD and scheduled for liver biopsy were enrolled at the Clinical Trial Center of our hospital between June 2024 and December 2024. All participants underwent both VCTE and 2D-SWE examinations on the same day as their liver biopsy, which served as the gold standard for assessing fibrosis. Diagnostic accuracy was analyzed using receiver operating characteristic (ROC) curves.

The areas under the ROC curves (AUCs) for 2D-SWE in diagnosing liver fibrosis (F ≥ 1) and significant fibrosis (F ≥ 2) were 0.92 (95% CI: 0.83-0.97) and 0.93 (95% CI: 0.85-0.98), respectively. The optimal cutoff values were 6.1 kPa and 7.66 kPa, yielding sensitivities of 87.8% and 84% and specificities of 85.3% and 94%, respectively. For VCTE, the AUCs were 0.84 (95% CI: 0.74-0.91) and 0.90 (95% CI: 0.81-0.96), with cutoff values of 6.3 kPa and 8.1 kPa, sensitivities of 92.7% and 76%, and specificities of 64.7% and 90%, respectively. No statistically significant difference was observed in the diagnostic performances of 2D-SWE and VCTE for liver fibrosis or significant fibrosis, with P-values of 0.09 and 0.44, respectively.

2D-SWE demonstrated high diagnostic accuracy for detecting liver fibrosis and significant fibrosis in MASLD patients, performing comparably to VCTE.

Metabolic dysfunction-associated steatotic fatty liver disease (MASLD) is a worsening global health issue, affecting over one-third of the adult population and representing the leading cause of liver-related morbidity and mortality. MASLD is not only a key precursor to chronic liver disease, but also a systemic condition that leads to numerous extrahepatic complications, increasing the risk of cardiovascular diseases, chronic kidney disease, type 2 diabetes, and certain cancers. The primary reference method for assessing liver fibrosis, allowing for precise determination of its location and severity, remains liver biopsy. However, it is an invasive procedure and involves certain risks. In recent years, the importance of MASLD diagnosis using noninvasive diagnostic methods has been increasing, including serological markers, methods based on multi-omics, and imaging techniques such as liver elastography. This review presents data on the diagnosis and evaluation of this disease that may find application in future clinical practice. The focus is on presenting both currently used and newly identified noninvasive diagnostic methods that open up the prospect of gradually replacing biopsy in the diagnosis of MASLD.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common chronic liver disease and represents a significant public health issue. Nevertheless, current risk stratification methods remain inadequate. The study aimed to use machine learning in the identification of significant features and the development of a predictive model to determine its usefulness in discrimination of MAFLD's risk stratification (low, moderate, and high) in adults.

The data of the 2021-2023 NHANES database were analyzed. Vibration-controlled transient elastography measurements, including controlled attenuation parameter for the evaluation of steatosis and liver stiffness for the evaluation of fibrosis, were used for risk stratification. The participants were grouped into low-risk, moderate-risk, and high-risk groups based on specific criteria. Feature selection was conducted through Least Absolute Shrinkage and Selection Operator (LASSO) regression and random forest classification.

A total of 4,227 participants were included in the study. There were 16 significant predictors identified by LASSO regression, among which the top 10 predictors were demographic (age, gender, race, hypertension history), clinical (body mass index, waist circumference, hemoglobin, glycohemoglobin, lymphocyte count), and education level. The area under the receiver operating characteristic curve (AUC) of the random forest model in the validation set was 0.80, and the individual AUC was 0.83, 0.66 and 0.79 for the low-, moderate-, and high-risk groups, respectively.

Our machine learning model has excellent performance in stratification of risk for MAFLD with readily available clinical and demographic parameters. This model could be employed as a valuable screening tool to refer high-risk patients for further hepatological evaluation.

Chronic liver disease affects over a billion people worldwide. Liver fibrosis is the key driver of liver-related complications and mortality. Elastography has been a transformative tool in hepatology, allowing for the diagnosis and staging of liver fibrosis noninvasively, and is evolving beyond these purposes into a prognostication tool. By measuring tissue stiffness, elastography techniques such as shear-wave and magnetic resonance elastography offer critical insights into liver fibrosis, portal hypertension, and the progression of disease. Magnetic resonance elastography stands out for its reliability across fibrosis stages and robustness in obese patients affected by metabolic liver disease. Spleen stiffness measurement complements liver assessments, enhancing the identification of portal hypertension and refining patient risk stratification. This review covers current clinical applications but also anticipates future innovations such as artificial intelligence-based algorithms that could expand elastography's clinical impact, thereby improving patient outcomes.

Therapeutic trials in metabolic dysfunction-associated steatohepatitis (MASH) are hampered by a high 70-80% screen failure rate mostly because of the absence of fibrotic MASH on baseline liver biopsies, underscoring the need for better selection of candidates. We compared the performance of eight non-invasive tests, designed or not for the diagnosis of fibrotic MASH.

A total of 1,005 patients with histologically proven MASLD were included in five tertiary care centers. Three non-invasive tests developed for fibrotic MASH were evaluated: the simple blood test Fibrotic NASH Index (FNI), the specialized blood test MACK-3, and the elastography-based test FAST. Five non-invasive tests recommended for advanced fibrosis were evaluated as well: the simple blood test FIB-4, the specialized blood tests FibroTest and Enhanced Liver Fibrosis test (ELF™), and the elastography-based tests FibroScan and Agile3+. Fibrotic MASH was defined as MASH with MASLD activity score ≥4 and fibrosis score F ≥2.

Among simple blood tests (n = 1,005), FNI had a significantly higher area under the receiver operating characteristic (AUROC) for fibrotic MASH than FIB-4 (0.709 [0.677-0.741] vs. 0.662 [0.628-0.695], p = 0.019). Among elastography-based tests (n = 817), FAST had a significantly higher AUROC (0.774 [0.743-0.806]) than FibroScan (0.728 [0.694-0.763], p = 0.013) and Agile3+ (0.708 [0.672-0.744], p = 0.004). Among specialized blood tests (n = 545), MACK-3 had a significantly higher AUROC (0.772 [0.734-0.811]) than FibroTest (0.615 [0.568-0.663], p <0.001) and ELF (0.700 [0.656-0.744], p = 0.028). Sequential combination (FAST then Agile3+; MACK-3 then ELF) identified a subset including one-third of patients in whom the false-positive rate was only 30%.

Sequential combinations using first-line tests designed for fibrotic MASH improves the identification of candidates for MASH therapeutic trials.

Drug development in metabolic dysfunction-associated steatohepatitis (MASH) is hampered by a high screen failure rate, one of the main reasons being the absence of MASH and significant fibrosis (fibrotic MASH) on the baseline liver biopsy, a key inclusion criterion in MASH therapeutic trials. Non-invasive tests represent an attractive opportunity to better select candidates for these trials, but most of them have been developed for advanced fibrosis and the new tests designed for the diagnosis of fibrotic MASH remain poorly validated. In this work, we demonstrate that the tests specifically designed for fibrotic MASH are more accurate for this diagnostic target than the tests currently recommended and initially developed for advanced fibrosis. We propose sequential combinations that will facilitate the identification of patients with fibrotic MASH in need of treatment, and their inclusion in MASH therapeutic trials.

To evaluate the concordance between vibration-controlled transient elastography (VCTE) and magnetic resonance elastography (MRE) for staging liver fibrosis and assessing hypothetical eligibility for resmetirom treatment in a cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). A secondary objective was to assess the performance of VCTE for liver fat quantification.

This retrospective study included 103 patients (61 males; mean age 54.7 years) with suspected MASLD who underwent VCTE and MRI/MRE. The following parameters were extracted: liver stiffness (LS) from both techniques, controlled attenuation parameter (CAP) from VCTE, and MRI-proton density fat fraction (PDFF). Agreement and fibrosis stage distributions were assessed using Cohen's Kappa and McNemar's tests. ROC analysis assessed the performance of CAP against MRI-PDFF (considered the reference for steatosis).

A significant difference was observed in assigned fibrosis stage distributions between VCTE and MRE across all combinations (F0-F1 vs F2-F4, F0-F2 vs F3-F4, F0-F3 vs F4, all p < 0.001) with fair to moderate agreement between modalities (Cohen's Kappa values 0.305-0.554). VCTE assigned a higher fibrosis stage in 42 patients (40.7%). Thirty-three vs eighteen patients were classified as F2-F3 (qualified for resmetirom treatment) with VCTE vs MRE (Cohen's Kappa 0.215), which was associated with estimated cost savings of $707,701/year with MRE. VCTE-CAP achieved AUCs of 0.547, 0.754, and 0.813 for diagnosing mild, moderate, and severe steatosis, respectively.

VCTE and MRE have fair to moderate agreement for fibrosis staging, with VCTE tending to assign a higher fibrosis stage compared to MRE. VCTE-CAP reliably detects only severe steatosis.

Question What is the agreement between VCTE and MRE in staging fibrosis in MASLD and identifying patients with F2-F3 disease? Findings Limited concordance was found between VCTE and MRE for staging liver fibrosis and identifying F2-F3 disease; VCTE tended to assign higher fibrosis stages compared to MRE. Clinical relevance MRE could represent the modality of choice for selecting patients with metabolic dysfunction-associated steatohepatitis for resmetirom therapy as it potentially offers high cost-savings compared to VCTE.

Increasing prevalence of metabolic dysfunction-associated liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) poses a growing healthcare burden. Noninvasive diagnostic tools to replace liver biopsy are urgently needed. We investigated the utility and cost-effectiveness of including multiparametric magnetic resonance imaging (mpMRI) to the management of adults with suspected MASLD multi-nationally.

RADIcAL-1, a 1:1 randomised controlled trial (standard-of-care [SoC] vs. imaging arm [IA; SoC+mpMRI]) included 802 participants from Germany, Netherlands, Portugal and UK. Wilcoxon-rank tests were used to compare access to healthcare practitioners, patient assessments and proportion of patients with a diagnosis (%diagnosis). Liver fat and disease activity (corrected T1 [cT1]) were used to identify patients not requiring biopsy in the imaging arm. Primary endpoint was mpMRI cost-effectiveness and improvement in resource use (visits avoided) using mpMRI.

mpMRI is cost-effective with an ICER of €4968/QALY gained. 403 were randomised to IA and 399 to SoC. SoC has significantly more specialist appointments (p = 0.015) and patient assessments (p < 0.001). Across all involved hospitals, %diagnosis is significantly higher in the imaging arm (p = 0.0012). cT1 correctly classifies 50% of patients without MASH with fibrosis and can avoid biopsy. Including all costs, the imaging arm incurs higher short-term per-patient healthcare expenditure compared to the SoC arm (€1,300 vs. €830).

Adding mpMRI to SoC for the management of adults with suspected MASLD multi-nationally is cost-effective, enhances rate of diagnosis multi-nationally and increases rate of diagnosis without increasing other liver-related health care resource use. Due to the need for standardisation of SoC, widespread use can support optimisation of the MASLD clinical pathway and improve long-term patient management.

The absence of hepatic fat in advanced fibrosis has been documented in metabolic dysfunction-associated steatotic liver disease (''burnt-out" MASLD). However, whether hepatic fat loss occurs continuously with fibrosis progression is controversial. We proposed a "burning-out" concept to describe this process and analyze the long-term outcomes of "burnt-out" and "burning-out" MASLD.

We included a MASLD cohort from 16 centers, including 3273 individuals with baseline histology and 5455 with serial vibration-controlled transient elastography measurements during the follow-up. "Burnt-out" MASLD was defined by steatosis grade ≤S1 and fibrosis stage ≥F3. Trajectory analysis identified "burning-out" patients with continuous trends of decreasing controlled attenuation parameter and increasing liver stiffness measurement values.

Of 3273 patients with histologic evaluation included, 435 had "burnt-out" MASLD. Compared with those with pronounced steatosis in advanced fibrosis, patients with "burnt-out" had higher risks of all-cause mortality (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.14-4.02), liver-related events (LREs; HR, 1.77; 95% CI, 1.12-2.78), and hepatic decompensation (HR, 1.83; 95% CI, 1.11-3.01). Of 5455 patients with vibration-controlled transient elastography included for trajectory analysis, 176 were identified as "burning-out" MASLD. The incidence rates of all-cause mortality, LREs, and decompensation were 7.28, 26.47, and 21.92 per 1000 person-years in "burning-out" patients, respectively. The "burning-out" group had higher cumulative incidences of adverse outcomes than patients with consistently high controlled attenuation parameter and moderate/low liver stiffness measurement values (P < .0001).

Continuous hepatic fat loss accompanied by fibrosis progression, referred to as "burning-out," was observed in advanced MASLD and associated with high rates of all-cause mortality, LREs, and hepatic decompensation.

The prevalence of obesity and metabolic syndrome (MetS) is rising among liver transplant (LT) candidates, many of whom have Metabolic-Associated Steatotic Liver Disease (MASLD). Following LT, untreated obesity often causes recurrent MASLD. We treated patients with obesity with LT and concurrent sleeve gastrectomy (LTSG), aiming to determine long-term impact on obesity, MetS and recurrent MASLD after transplantation.

A multicenter retrospective cohort study analyzed patients undergoing LTSG using a single clinical protocol (n=72), and patients with BMI >30 who underwent LT alone for MASLD (n=185). Follow-up duration was 4-153 (median 41) months for LTSG and 12-161 (median 75) months for LT. Outcomes included mortality, graft loss, BMI, MetS components, allograft steatosis and fibrosis.

Mortality and graft loss were not significantly different between LT and LTSG patients. Post-LTSG patients had significantly lower prevalence of diabetes for >8 years (p<0.05); hypertension decreased from 61.1% to 35.8% (p<0.01). LTSG patients, with average starting BMI of 45.5, had significant weight loss compared to baseline for >9 years (p<0.001). LT-alone patients, average starting BMI 34.0, experienced no significant change in BMI or diabetes. Development of allograft steatosis was significantly lower in LTSG vs LT patients (p=0.004). Fibrosis prevalence was reduced in LTSG vs LT patients 3-10 years postoperatively; although not statically significant, relative risk ratio was 0.46 (p=0.09). One LTSG patient had a gastric sleeve leak; one required hiatal hernia repair. Severe GERD occurred in 11.1% of LTSG patients; risk factors included pre-existing diabetes and GERD.

LTSG results in sustained weight loss, resolution of diabetes and hypertension, and reduced recurrence of steatosis and possibly fibrosis compared to LT alone. It confers no increase in mortality or graft loss.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the umbrella term that comprises metabolic dysfunction-associated steatotic liver, or isolated hepatic steatosis, through to metabolic dysfunction-associated steatohepatitis, the progressive necroinflammatory disease form that can progress to fibrosis, cirrhosis and hepatocellular carcinoma. MASLD is estimated to affect more than one-third of adults worldwide. MASLD is closely associated with insulin resistance, obesity, gut microbial dysbiosis and genetic risk factors. The obesity epidemic and the growing prevalence of type 2 diabetes mellitus greatly contribute to the increasing burden of MASLD. The treatment and prevention of major metabolic comorbidities such as type 2 diabetes mellitus and obesity will probably slow the growth of MASLD. In 2023, the field decided on a new nomenclature and agreed on a set of research and action priorities, and in 2024, the US FDA approved the first drug, resmetirom, for the treatment of non-cirrhotic metabolic dysfunction-associated steatohepatitis with moderate to advanced fibrosis. Reliable, validated biomarkers that can replace histology for patient selection and primary end points in MASH trials will greatly accelerate the drug development process. Additionally, noninvasive tests that can reliably determine treatment response or predict response to therapy are warranted. Sustained efforts are required to combat the burden of MASLD by tackling metabolic risk factors, improving risk stratification and linkage to care, and increasing access to therapeutic agents and non-pharmaceutical interventions.

To determine the ultrasound shear wave elastography (SWE)-based prevalence of chronic liver disease in an adult Asian Indian population attending preventive radiology outpatient clinics in India.

Liver stiffness measures (LSMs) were ascertained using ultrasound SWE and interquartile range/median (IQR/M) ratio ≤ 30% kilopascal (kPa) units were considered a good quality measurement. Details of modifiable risk factors including comorbidity and personal risk behaviors were collected. The liver was graded based on the Society of Radiologists in Ultrasound Liver Elastography Consensus Statement and Grades 4 and 5 indicated compensated advanced chronic liver disease (cACLD) and clinically significant portal hypertension (CSPH). A multivariate logistic regression model was used to analyze associations with chronic advanced liver disease.

The median LSM in the study participants (n = 1145) was 8.0 (IQR 6.5, 9.85) kPa units. 10.65% of the study population had advanced chronic liver disease (cACLD and CSPH) and 22.79% had LSM that was suggestive of cACLD. cACLD and CSPH were significantly associated with comorbidities, personal risk behaviors, and lean and obese body mass indices. Modifiable risk factors were present in 20%-50% of participants with LSM between 7 and 13 kPa.

Information on the prevalence of LSM-based cACLD and CSPH and modifiable risk factors in persons with LSM between 7 and 13 kPa will help to design preventative strategies using LSM as an objective imaging biomarker.

Non-alcoholic fatty liver disease (NAFLD)-related liver fibrosis is closely associated with long-term outcomes of patients. This study aimed to establish a transcriptome signature to distinguish NAFLD patients with mild or advanced fibrosis and to monitor disease progression. Using least absolute shrinkage selection operator regression, we identified a signature of 11 hub genes by performing differential gene expression analysis in six bulk transcriptome profiles in the Gene Expression Omnibus database from liver fibrosis patients with different etiologies. Patients with NAFLD were classified using the 11-hub gene signature. Integrated analysis of signaling pathway enrichment, gene set enrichment, nearest template prediction, infiltration by hepatic stellate cells (HSCs) and pseudotime trajectories was performed on three bulk and one single-cell transcriptomes from NAFLD patients. Molecular features were compared between high-risk and low-risk groups, and associations were explored between hub gene signature expression and activation of HSCs. It was found that the high-risk group was characterized by advanced fibrosis stage, elevated risk for hepatocellular carcinoma, more significant infiltration by activated HSCs, as well as enrichment in signaling pathways related to fibrogenesis and NAFLD progression. Moreover, the 11-hub gene signature at the single-cell transcriptome level correlated with HSCs activation. In vitro experiments were conducted to evaluate the expression levels of hub genes, and IL6 was found to be up-regulated in activated LX-2 cells showing lipid accumulation. Our findings suggest that the 11-hub gene signature can help identify fibrosis stage in patients with NAFLD and detect disease progression. We also suggest that the role of IL6 in HSC activation deserves more investigation in the context of NAFLD.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of liver disease worldwide. In patients with MASLD, liver fibrosis stage is the most significant predictor of mortality; therefore, early identification of patients at the greatest risk of advanced fibrosis is essential. Noninvasive tests predict advanced fibrosis and are recommended for use in primary care settings to determine which patients would benefit most from specialty care. The adoption of these tools is not widespread, and several studies have reported underrecognition of cirrhosis in patients with MASLD and diabetes. The finding of hepatic steatosis on imaging performed for evaluation of nonliver conditions may present an avenue for opportunistic screening to identify more patients with MASLD. This article will review recommendations for when hepatic steatosis is found on imaging and noninvasive tests that can be used to help predict fibrosis staging. This is a significant area of research because a new treatment for MASLD has been approved, and other treatments may follow.

Cirrhosis is a major cause of morbidity and mortality; however, there are no approved therapies except orthotopic liver transplantation. Preclinical studies showed that bone-marrow-derived macrophage injections reduce inflammation, resolve fibrosis and stimulate liver regeneration. In a multicenter, open-label, parallel-group, phase 2 randomized controlled trial ( ISRCTN10368050 ) in n = 51 adult patients with compensated cirrhosis and Model for End-Stage Liver Disease (MELD) score ≥10 and ≤17, we evaluated the efficacy of autologous monocyte-derived macrophage therapy (n = 27) compared to standard medical care (n = 24). The primary endpoint was the difference in baseline to day 90 change in MELD score (ΔMELD) between treatment and control groups (ΔΔMELD). Secondary endpoints included adverse clinical outcomes, non-invasive fibrosis biomarkers and health-related quality of life (HRQoL) at 90 d, 180 d and 360 d. The ΔΔMELD between day 0 and day 90 in the treatment group compared to controls was -0.87 (95% confidence interval: -1.79, 0.0; P = 0.06); therefore, the primary endpoint was not met. During 360-d follow-up, five of 24 participants in the control group developed a total of 10 severe adverse events, four of which were liver related, and three deaths (two liver related), whereas no liver-related severe adverse events or deaths occurred in the treatment group. Although no differences were observed in biomarkers or HRQoL, exploratory analysis showed anti-inflammatory serum cytokine profiles after macrophage infusion. This study reinforces the safety and potential efficacy of macrophage therapy in cirrhosis, supporting further investigation.

To compare the diagnostic test accuracy (DTA) of shear wave elastography (SWE) to that of transient elastography (TE) for liver fibrosis grade assessment in nonalcoholic fatty liver disease adults.

MEDLINE, The Cochrane Library, and Web of Science were searched. Inclusion criteria were primary studies examining DTA of TE, point SWE (pSWE), two-dimensional SWE (2D-SWE), or magnetic resonance elastography (MRE) with liver biopsy. Network meta-analysis was conducted using a Bayesian bivariate mixed-effects model.

For fibrosis grade 2 or higher, 15 studies with 25 observations (16 observations for TE, 1 for MRE, 4 for pSWE and 2D-SWE; 2,066 patients) were included; the pooled sensitivity and specificity were 0.79 (95% credible interval (CrI) 0.70-0.86; 95% prediction interval (PI) 0.36-0.96) and 0.73 (95% CrI 0.62-0.82; 95% PI 0.23-0.96) for TE, 0.68 (95% CrI 0.48-0.83; 95% PI 0.23-0.94) and 0.75 (95% CrI 0.53-0.88; 95% PI 0.24-0.97) for pSWE, 0.85 (95% CrI 0.70-0.93; 95% PI 0.40-0.98) and 0.72 (95% CrI 0.49-0.86; 95% PI 0.20-0.96) for 2D-SWE, respectively. The proportion of studies classified as unclear in QUADAS-2 was high, and the results were heterogeneous.

2D-SWE could be recommended as TE is for liver fibrosis assessment. The protocol of this systematic review and network meta-analysis has been registered in PROSPERO (CRD42022327249). All included primary papers have already been published and the information and data can be used freely.

Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.

There is limited data on the association between TyG-BMI and NAFLD in patients with Type 2 Diabetes Mellitus (T2DM). The magnitude of risk prediction and predictive efficacy of TyG-BMI for T2DM with NAFLD remains unclear.

To examine the association of TyG-BMI with NAFLD in T2DM patients and assess the effectiveness of screening using the TyG-BMI index.

We conducted a retrospective analysis of clinical data from 602 T2DM patients at an enterprise health lodge from September 2021 to November 2022. Patients were categorized into two groups: T2DM alone (n=250) and T2DM with NAFLD (n=352). The Mann-Whitney U test was used for comparing non-normally distributed continuous data between groups, while the Chi-square test was used for categorical data. Logistic regression analysis was performed to evaluate the effect of BMI, TyG index, and TyG-BMI index on NAFLD. The ROC curve was used to assess the predictive efficacy of the TyG-BMI index for NAFLD in T2DM patients.

BMI predicted the development of NAFLD in T2DM patients with an area under the receiver operating characteristic (ROC) curve of 0.792 (95% CI 0.757-0.828), and the optimal cutoff value was 25.22, with 72.2% sensitivity and 71.6% specificity; The area under the receiver operating characteristic (ROC) curve of the TyG index to predict the development of NAFLD in patients with T2DM was 0.755 (95% CI 0.716-0.794), and the optimal cutoff value was 8. 945, with a sensitivity of 80.1% and a specificity of 59.2%; The area under the receiver operating characteristic (ROC) curve of TyG-BMI index to predict the development of NAFLD in T2DM patients was 0.852, (95% CI 0.822-0.882), and the optimal cutoff value was 227.385, with a sensitivity and specificity of 80.1% and 59.2%, respectively.

The TyG-BMI index is a significant predictor of comorbid NAFLD in T2DM patients and provides better screening performance than BMI alone. The TyG-BMI index shows promise as an early screening tool for NAFLD in T2DM patients.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease worldwide, with a multifactorial etiology. This study aims to evaluate the associations between various sociodemographic variables, healthy habits, and stress with risk scale values for MAFLD.

A descriptive, cross-sectional study was conducted on 16,708 Spanish workers to assess how sociodemographic variables (age, gender, and socioeconomic status), healthy habits (smoking, Mediterranean diet adherence, and physical activity), and stress correlate with values from three MAFLD risk scales: fatty liver index (FLI), hepatic steatosis index (HSI), and lipid accumulation product (LAP).

All analyzed variables were associated with the values of the three MAFLD risk scales. Among them, the variables showing the strongest associations (represented by odds ratio values) were age and physical activity.

The profile of an individual at higher risk of elevated MAFLD risk scale values is a male, aged 50 or older, belonging to lower socioeconomic levels (manual laborers), a smoker, sedentary, with low adherence to the Mediterranean diet, and with high stress scale scores.

Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with chronic inflammation and lipid metabolism disorders. The neutrophil-to-high-density lipoprotein cholesterol ratio (NHR) is an integrative marker reflecting inflammatory responses and lipid metabolism disorders and is associated with various diseases. This cross-sectional study aimed to determine the association between NHR and NAFLD, MASLD, and liver fibrosis.

Data for this study were obtained from the 2017-2020 National Health and Nutrition Examination Survey (NHANES), we employed weighted multiple regression and restricted cubic spline (RCS) analysis to assess the relationship between NHR and NAFLD, MASLD, and liver fibrosis. Additionally, we performed stratified analyses based on gender, age, body mass index, diabetes, hypertension, smoking status, and history of cardiovascular disease to evaluate the consistency of these associations across different subgroups.

A total of 6,526 participants were included in the study. 2,839 (weighted 44.1%) participants were diagnosed with NAFLD and 2,813 (weighted 43.7%) participants were diagnosed with MASLD. After adjusting for confounders, NHR was positively associated with the risk of NAFLD/MASLD, and the correlation was particularly significant in the subgroups of females, those without hypertension, and those without diabetes (p < 0.05). By the NHR quartile, the risk of NAFLD/MASLD increased progressively with higher NHR levels (P for trend <0.001). In addition, RCS analysis showed a nonlinear association between NHR and NAFLD/MASLD and liver fibrosis (P-non-linear <0.05).

NHR may serve as a potential marker for NAFLD/MASLD and liver fibrosis, and lowering NHR levels could help reduce the incidence of these conditions.

The purpose of this systematic review and meta-analysis was comparing diagnostic performance of ultrasound elastography (UE), strain UE and shear wave elastography (SWE), with magnetic resonance imaging (MRI) in differentiating benign and malignant breast lesions.

Literature search of MEDLINE, Web of Science, SCOPUS and Google Scholar was performed in June 2023. Included studies used Breast Imaging Reporting and Data System (BI-RADS) and histopathology as reference standard. A bivariate random-effects model was used to calculate sensitivity, specificity, diagnostic odds ratio (DOR), positive and negative likelihood ratios and area under the curve (AUC). Meta-regression subgroup analysis was performed.

Nine studies and 536 lesions were included. Pooled sensitivity was not different between MRI vs UE [MRI: 94% (95% CI: 88.2%-96.9%) vs UE: 90% (95% CI: 84.7%-93.1%); P=0.153] but a difference was found for specificity [UE: 78% (95% CI: 66.3%-86.4%) vs MRI: 71.3% (95% CI: 52.1%-85%); P=0.0065]. Strain UE showed higher specificity and similar sensitivity to SWE [strain UE: 0.85 (95% CI: 0.71-0.93) vs SWE: 0.72 (95% 0.58-0.83); P=0.017 and strain UE: 0.87 (95% CI 0.79-0.93) vs SWE: 0.91 (95% CI 0.85-0.95); P=0.311, respectively]. AUC was similar between MRI vs UE [0.91 (95% CI 0.87-0.95) vs 0.92 (95% CI 0.88-0.95); P=0.452, respectively] as was DOR [MRI: 38.083 (95% CI: 12.401-116.957) vs UE: 30.395 (95% CI: 16.572-55.75); P>0.05]. Meta-regression analysis found no significant differences in the diagnostic accuracy between MRI, strain UE and SWE.

Our results show that UE when compared to MRI has adequate performance in differentiating benign and malignant breast lesions.

Background: The aim of this study was to investigate the accuracy in fibrosis staging of a novel shear wave elastography (SWE) device (S-Shearwave Imaging by Samsung) and a previously validated 2D-SWE by Supersonic Imagine (SSI) in patients with biopsy proven metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: This prospective study included 75 consecutive patients with MASLD who underwent liver biopsy for suspected MASH. All patients underwent S-Shearwave Imaging by Samsung and 2D-SWE with SSI on the same day of liver biopsy. Fibrosis was histologically assessed using the METAVIR classification system. Agreement between the equipment was assessed with the Pearson coefficient. A receiver operator characteristic curve (ROC) analysis with the Youden index was used to establish thresholds for fibrosis staging. Results: A good correlation was found between S-Shearwave Imaging by Samsung and 2D-SWE with SSI (Pearson's R = 0.68; p < 0.01). At multivariate regression analysis, S-Shearwave Imaging was associated with advanced fibrosis (≥F3) independently from age, diabetes and platelets (OR 2.94, CI 1.69-5.11, p < 0.01). The fibrosis diagnostic accuracy of both S-Shearwave Imaging and 2D-SWE was good to optimal with AUROCs of 0.81 and 0.70 for significant fibrosis (≥F2), 0.94 and 0.91 for severe fibrosis (≥F3), respectively. The accuracy of S-Shearwave is not significantly different from Fibroscan and Agile3+ (DeLong test p value 0.16 and 0.15, respectively) while is slightly better than 2D-SWE, FIB4 and NFS (DeLong test p value < 0.05). For S-Shearwave Imaging by Samsung, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.9 kPa (Sens 74.4%, Spec 87.5%) and 8.1 kPa (Sens 95.6%, Spec 78.8%). For 2D-SWE by SSI, the best cut-off values for diagnosing fibrosis ≥F2, ≥F3 were, respectively, 7.2 kPa (Sens 55.8%, Spec 84.4%) and 7.6 kPa (Sens 82.6%, Spec 84.6%). Conclusion: S-Shearwave Imaging is a useful and reliable non-invasive technique for staging liver fibrosis in patients with MASLD. Its diagnostic accuracy is non-inferior to other shear wave elastography techniques (TE and 2D-SWE by SSI).

In children and adults, quantitative imaging examinations determine the effectiveness of treatment for liver disease. However, pediatric liver disease differs in presentation from liver disease in adults. Children also needed to be followed for a longer period from onset and have less control of their bodies, showing more movement than adults during imaging examinations, which leads to a greater need for sedation. Thus, it is essential to appropriately tailor and accurately perform noninvasive imaging tests in these younger patients. This article is an overview of updated imaging techniques used to assess liver disease quantitatively in children. The common initial imaging study for diffuse liver disease in pediatric patients is ultrasound. In addition to preexisting echo analysis, newly developed attenuation imaging techniques have been introduced to evaluate fatty liver. Ultrasound elastography is also now actively used to evaluate liver conditions, and the broad age spectrum of the pediatric population requires caution to be taken even in the selection of probes. Magnetic resonance imaging (MRI) is another important imaging tool used to evaluate liver disease despite requiring sedation or anesthesia in young children because it allows quantitative analysis with sequences such as fat analysis and MR elastography. In addition to ultrasound and MRI, we review quantitative imaging methods specifically for fatty liver, Wilson disease, biliary atresia, hepatic fibrosis, Fontan-associated liver disease, autoimmune hepatitis, sinusoidal obstruction syndrome, and the transplanted liver. Lastly, concerns such as growth and motion that need to be addressed specifically for children are summarized.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most widespread chronic liver disease that poses significant threats to public health due to changes in dietary habits and lifestyle patterns. The transition from simple steatosis to nonalcoholic steatohepatitis (NASH) markedly increases the risk of developing cirrhosis, hepatocellular carcinoma, and liver failure in patients. However, there is only one Food and Drug Administration-approved therapeutic drug in the world, and the clinical demand is huge. There is significant clinical heterogeneity among patients with NAFLD, and it is challenging to fully understand human NAFLD using only a single animal model. Interestingly, felines, like humans, are particularly prone to spontaneous fatty liver disease. This review summarized and compared the etiology, clinical features, pathological characteristics, and molecular pathogenesis between human fatty liver and feline hepatic lipidosis (FHL). We analyzed the key similarities and differences between those two species, aiming to provide theoretical foundations for developing effective strategies for the treatment of NAFLD in clinics.

Metabolic dysfunction-associated steatotic liver disease (MASLD) imposes significant health care burdens. Early detection of advanced fibrosis and cirrhosis in MASLD is essential due to their unfavorable outcomes. This multilevel random-effects meta-analysis aimed to provide the best evidence for the diagnostic accuracy of 2-dimensional shear wave elastography in detecting liver fibrosis in biopsy-proven MASLD.

This study involves systematic search in PubMed/MEDLINE, Embase, Scopus, Web of Science, LILACS, and Cochrane Library electronic databases for full-text articles published in any language up to February 26, 2024. Included studies reported liver stiffness measurement by 2-dimensional shear wave elastography and used histological diagnosis as the gold standard. A linear mixed-effects multiple thresholds model was employed, and summary estimates for sensitivity, specificity (Sp), and summary area under the receiver operator characteristic curve were computed. Twenty observational studies (SuperSonic Imagine, General Electric Healthcare, and Canon Medical Systems) fulfilled the inclusion criteria, comprising 2223 participants with biopsy-proven MASLD. The prevalence of mild fibrosis (F1), significant fibrosis (F2), advanced fibrosis (F3), and cirrhosis (F4) was 30.0%, 18.5%, 17.9%, and 10.9%, respectively. The summary area under the receiver operator characteristic curve [95% CI] in detecting ≥F1, ≥F2, ≥F3, and F4 for all ultrasound machines considered together were 0.82 [0.16-0.98], 0.82 [0.76-0.88], 0.86 [0.77-0.93], and 0.89 [0.80-0.95], respectively. The optimal cutoff values were 6.432 kPa for ≥F1, 8.174 kPa for ≥F2, 9.418 kPa for ≥F3, and 11.548 kPa for F4, respectively.

Our meta-analysis identified optimized cutoffs for fibrosis staging by 2-dimensional shear wave elastography in etiology-specific chronic liver diseases (MASLD), with excellent diagnostic performance, underscoring the potential for standardizing cutoff values.

New scores were developed to identify at-risk metabolic dysfunction-associated steatohepatitis (MASH) using multiparametric MRI (mpMRI).

A prospective study was conducted on 176 patients with suspected or diagnosed metabolic dysfunction-associated steatotic liver disease (MASLD) paired with an MR scan, vibration-controlled transient elastography (VCTE), and liver biopsy. Liver stiffness measurement (LSM) using magnetic resonance elastography (MRE), proton density fat fraction (PDFF), and mpMRI-based corrected T1 (cT1) were combined to develop a one-step strategy, named MPcT (MRE + PDFF + cT1, combined score), and a two-step strategy-MRE-based LSM followed by PDFF with cT1 (M-PcT, paired score) for diagnosing at-risk MASH. Each model was categorized using rule-in and rule-out criteria (three categorized analyses). To avoid overfitting, the diagnostic accuracies were evaluated based on 5-fold cross-validation.

PDFF + cT1 (PcT) had the highest diagnostic performance for severe activity (hepatic inflammation plus ballooning grade ≥ 3) and for NAS ≥ 4 (active MASH). Areas under receiver operating characteristic curves (AUROCs) of M-PcT (0.832) for detecting at-risk MASH were significantly higher than those of Fibroscan-AST (FAST) (0.744, p = 0.017), MRI-AST (MAST) (0.710, p = 0.002), and MPcT (0.695, p < 0.001) in three categorized analysis. Following the rule-in criteria, positive predictive values of M-PcT (84.5%) were higher than those of FAST (73.5%), MAST (70.0%), and MPcT (66.7%). Following the rule-out criteria, negative predictive values of M-PcT (88.7%) were higher than those of FAST (84.0%), MAST (73.9%), and MPcT (84.9%).

The two-step strategy, M-PcT (paired score), showed the reliability of rule-in/-out for at-risk MASH, with better predictive performance compared with FAST and MAST (combined score).

This study is registered with ClinicalTrials.gov (number, UMIN000012757).

Question There is no mpMRI-based method for detecting as-risk MASH (NAFLD activity score ≥ 4 with fibrosis stage ≥ 2) like FAST and MAST scores. Findings MRE-based LSMs followed by PDFF with cT1 (M-PcT) were more useful in detecting at-risk MASH than the combined score (FAST and MAST). Clinical relevance By combining MRE and PDFF with cT1, it becomes possible to evaluate the pathology of MASH without the need for a liver biopsy, assisting in prognosis prediction and decision-making for treatment options.

Researchers have delved into noninvasive diagnostic methods of renal fibrosis (RF) in chronic kidney disease, including ultrasound (US), magnetic resonance imaging (MRI), and radiomics. However, the value of these diagnostic methods in the noninvasive diagnosis of RF remains contentious. Consequently, the present study aimed to systematically delineate the accuracy of the noninvasive diagnosis of RF.

A systematic search covering PubMed, Embase, Cochrane Library, and Web of Science databases for all data available up to 28 July 2023 was conducted for eligible studies.

We included 21 studies covering 4885 participants. Among them, nine studies utilized US as a noninvasive diagnostic method, eight studies used MRI, and four articles employed radiomics. The sensitivity and specificity of US for detecting RF were 0.81 (95% CI: 0.76-0.86) and 0.79 (95% CI: 0.72-0.84). The sensitivity and specificity of MRI were 0.77 (95% CI: 0.70-0.83) and 0.92 (95% CI: 0.85-0.96). The sensitivity and specificity of radiomics were 0.69 (95% CI: 0.59-0.77) and 0.78 (95% CI: 0.68-0.85).

The current early noninvasive diagnostic methods for RF include US, MRI, and radiomics. However, this study demonstrates that US has a higher sensitivity for the detection of RF compared to MRI. Compared to US, radiomics studies based on US did not show superior advantages. Therefore, challenges still exist in the current radiomics approaches for diagnosing RF, and further exploration of optimized artificial intelligence (AI) algorithms and technologies is needed.

Although noninvasive tests can be used to predict liver fibrosis, their accuracy is limited for patients with severe obesity and nonalcoholic fatty liver disease (NAFLD). We developed machine learning (ML) models to predict significant liver fibrosis in patients with severe obesity through noninvasive tests.

This prospective study included 194 patients with severe obesity who underwent wedge liver biopsy and metabolic bariatric surgery at Taipei Medical University Hospital between September 2016 and December 2020. Significant liver fibrosis was defined as a fibrosis score ≥ 2. Patients were randomly divided into a training group (70%) and a validation group (30%). ML models, including support vector machine, random forest, k-nearest neighbor, XGBoost, and logistic regression, were trained to predict significant liver fibrosis, using DM status, AST, ALT, ultrasonographic fibrosis scores, and liver stiffness measurements (LSM). An ensemble model including these ML models was also used for prediction.

Among the ML models, the XGBoost model exhibited the highest AUROC of 0.77, with a sensitivity, specificity, and accuracy of 61.5%, 75.8%, and 69.5%, in validation set, while LSM, AST, ALT showed strongest effects on the model. The ensemble model outperformed all ML models in terms of sensitivity, specificity, and accuracy of 73.1%, 90.9%, and 83.1%.

For patients with severe obesity and NAFLD, the XGBoost model and the ensemble model exhibit high predictive performance for significant liver fibrosis. These models may be used to screen for significant liver fibrosis in this patient group and monitor treatment response after metabolic bariatric surgery.

Non-invasive methods to diagnose non-alcoholic steatohepatitis (NASH), an inflammatory subtype of non-alcoholic fatty liver disease (NAFLD), are currently unavailable.

To develop an integrin αvβ3-targeted molecular imaging modality to differentiate NASH.

Integrin αvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids (FFA). Hepatic integrin αvβ3 expression was analyzed in rabbits fed a high-fat diet (HFD) and in rats fed a high-fat, high-carbohydrate diet (HFCD). After synthesis, cyclic arginine-glycine-aspartic acid peptide (cRGD) was labeled with gadolinium (Gd) and used as a contrast agent in magnetic resonance imaging (MRI) performed on mice fed with HFCD.

Integrin αvβ3 was markedly expressed on FFA-cultured hepatocytes, unlike the control hepatocytes. Hepatic integrin αvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver (FL) progressed to steatohepatitis. The distribution of integrin αvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas. In comparison to mice with simple FL, the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis (P < 0.05), showing a positive correlation with the NAFLD activity score (r = 0.945; P < 0.01). Hepatic integrin αvβ3 expression was significantly upregulated during NASH development, with hepatocytes being the primary cells expressing integrin αvβ3.

After using Gd-labeled cRGD as a tracer, NASH was successfully distinguished by visualizing hepatic integrin αvβ3 expression with MRI.

Liver fibrosis, a critical predictor of the prognosis of metabolic dysfunction-associated steatotic liver disease (MASLD), is traditionally diagnosed via biopsy. Nevertheless, non-invasive alternatives, such as serum biomarkers, vibration-controlled transient elastography, and magnetic resonance elastography, have become prominent because of the limitations of biopsies. Serum biomarkers, such as fibrosis-4 index and NFS Score, are also used widely, offering reliable diagnostic performance for advanced fibrosis. Vibration-controlled transient elastography and shear wave elastography provide further non-invasive evaluations with high diagnostic accuracy, particularly for advanced fibrosis, but the results may be affected by factors such as obesity. Magnetic resonance elastography, with superior diagnostic accuracy and operator independence, is a promising method, but its high cost and limited availability restrict its widespread use. Emerging algorithms, such as NIS4, FAST, or MAST score, have strong potential in identifying high-risk metabolic dysfunction-associated steatohepatitis patients. The integration of multiple non-invasive methods can optimize diagnostic accuracy, reducing the need for invasive biopsies while identifying patients at risk of liver-related complications. Further research is needed to refine these diagnostic tools and improve accessibility.

A noteworthy proportion of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have an indeterminate vibration-controlled transient elastography (VCTE). Among these patients, we aimed to identify candidates for MASLD treatment by diagnosing significant fibrosis.

This was a real-world prospective study including a large dataset of MASLD patients with paired VCTE and liver biopsy from 6 centers. A total of 1196 patients were recruited and divided in training (3 centers, Spain), internal validation (2 centers, Spain), and external validation (1 center, United States) cohorts. In patients with indeterminate liver stiffness measurement (LSM) (8-12 kPa), a diagnostic algorithm was developed to identify significant fibrosis, defined as histological stage ≥F2. Statistical analysis was performed using Gaussian mixture model (GMM) and k-means unsupervised clusterization.

From the eligible population, 33%, 29%, and 31% had indeterminate VCTE in the training, internal and external validation samples, respectively. The controlled attenuation parameter allowed the differentiation of GMM clusters with a cutoff of 280 dB/m (area under the curve, 0.89; 95% confidence interval, 0.86-0.97). Within patients with <280 dB/m, a LSM between 8.0-9.0 kPa showed a 93% sensitivity and a 91% negative predictive value to exclude significant fibrosis. Among patients with ≥280 dB/m, a LSM between 10.3 and 12.0 kPa diagnosed significant fibrosis with a 91% specificity. Applying this algorithm to the validation cohorts, 36% of the indeterminate VCTE were reallocated. The reallocated high-risk group showed a prevalence of 86% significant fibrosis, opening the therapeutic window for MASLD patients.

To identify candidates for MASLD treatment among indeterminate VCTE, an algorithm-based on the sequential combination of LSM and controlled attenuation parameter thresholds can optimize the diagnosis of moderate-to-advanced fibrosis.

Accurate staging of liver fibrosis (LF) is essential for clinical management in chronic liver disease. While non-contrast MRI (NC-MRI) yields valuable information for liver assessment, its effectiveness in predicting LF remains underexplored. This study aimed to develop and validate artificial intelligence (AI)-powered models utilizing NC-MRI for staging LF.

A total of 1726 patients from Shengjing Hospital of China Medical University, registered between October 2003 and October 2022, were retrospectively collected, and divided into development (n = 1208) and internal test (n = 518) cohorts. An external test cohort consisting of 337 individuals from six centers, registered between June 2015 and November 2022, were also included. All participants underwent NC-MRI (T1-weighted imaging, T1WI; and T2-fat-suppressed imaging, T2FS) and liver biopsies. Two classification models (CMs), named T1 and T2FS, were trained on respective image types using 3D contextual transformer networks and evaluated on both test cohorts. Additionally, three CMs-Clinic, Image, and Fusion-were developed using clinical features, T1 and T2FS scores, and their integration via logistic regression. Classification effectiveness of CMs was assessed using the area under the receiver operating characteristic curve (AUC). A comparison was conducted between the optimal models (OMs) with highest AUC and other methods (transient elastography, five serum biomarkers, and six radiologists).

Fusion models (i.e., OM) yielded the highest AUC among the CMs, achieving AUCs of 0.810 for significant fibrosis, 0.881 for advanced fibrosis, and 0.918 for cirrhosis in the internal test cohort, and 0.808, 0.868, and 0.925, respectively, in the external test cohort. The OMs demonstrated superior performance in AUC, significantly surpassing transient elastography (only for staging ≥ F2 and ≥ F3 grades), serum biomarkers, and three junior radiologists for staging LF. Radiologists, with the aid of the OMs, can achieve a higher AUC in LF assessment.

AI-powered models utilizing NC-MRI, including T1WI and T2FS, accurately stage LF.

National Natural Science Foundation of China (No. 82071885); General Program of the Liaoning Provincial Department of Education (LJKMZ20221160); Liaoning Province Science and Technology Joint Plan (2023JH2/101700127); the Leading Young Talent Program of Xingliao Yingcai in Liaoning Province (XLYC2203037).