To assess the association between sociodemographic variables and lifestyle habits with the risk of metabolic dysfunction-associated fatty liver disease (MASLD) in Spanish healthcare workers.

A cross-sectional study including 44,939 healthcare workers. Sociodemographic variables (age, sex, occupation) and lifestyle habits (smoking, physical activity, adherence to the Mediterranean diet) were analyzed in relation to MASLD risk scores (FLI, HSI, LAP, ZJU, and FLD). Multinomial logistic regression models were used to identify significant associations.

Higher risk score values were more prevalent in men and increased with age. Nursing assistants and orderlies had a higher risk compared to physicians. Physical inactivity (OR=2.65; 95% CI: 2.47-2.84) and low adherence to the Mediterranean diet (OR=1.89; 95% CI: 1.69-2.10) were associated with an increased risk of MASLD. Smoking was significantly related to higher risk scores (OR=1.17; 95% CI: 1.13-1.21).

Age, sex, occupation, smoking, physical activity, and adherence to the Mediterranean diet influence MASLD risk. Preventive strategies should focus on promoting physical activity, improving dietary habits, and reducing smoking among healthcare workers.

Non-alcoholic fatty liver disease (NAFLD) is a major global health concern, with rising prevalence linked to obesity, insulin resistance, and metabolic syndrome. Timely and accurate identification of individuals at risk is crucial for improving outcomes. Recently, systemic inflammatory and nutritional markers such as the Neutrophil Percentage-to-Albumin Ratio (NPAR) and the Neutrophil-to-Albumin Ratio (NAR) have emerged as promising non-invasive biomarkers for NAFLD. Both ratios reflect inflammation and hepatic nutritional status, offering potential utility in predicting disease presence and progression. This systematic review and meta-analysis aimed to evaluate the diagnostic value of NPAR and NAR in patients with NAFLD.

A comprehensive search was performed across databases including PubMed, Embase, Scopus, and Web of Science from inception to December 28, 2024. Data extraction was carried out using a standardized form, and the methodological quality of included studies was assessed using the Newcastle-Ottawa Scale. Statistical analyses were performed using STATA version 18, employing a random-effects model.

The meta-analysis demonstrated that both the Neutrophil Percentage-to-Albumin Ratio (NPAR) and the Neutrophil-to-Albumin Ratio (NAR) were significantly higher in patients with NAFLD compared to healthy individuals. NPAR showed a standardized mean difference (SMD) of 0.28 (95% CI: 0.22-0.35, P < 0.01), while NAR had a higher effect size with an SMD of 0.69 (95% CI: 0.44-0.93, P < 0.01). The pooled diagnostic performance of NPAR yielded a sensitivity of 69.5% (95% CI: 56.3-82.6%), specificity of 63.1% (95% CI: 46.6-70.0%), and an area under the curve (AUC) of 76.05% (95% CI: 66.3-85.7%). For NAR, the pooled sensitivity was 65.0% (95% CI: 49.0-82.0%), specificity was 63.0% (95% CI: 47.0-79.0%), and AUC was 69.0% (95% CI: 48.0-89.0%).

In conclusion, both NPAR and NAR were found to be elevated in individuals with NAFLD, supporting their potential as non-invasive and accessible biomarkers. These ratios reflect key aspects of systemic inflammation and nutritional status, offering clinical value in early detection and risk stratification. However, given the limited number of studies available-particularly for NAR-further research is needed to confirm these findings, establish standardized thresholds, and assess their performance across diverse populations and clinical settings.

Not applicable.

To evaluate the diagnostic performance of multisample point shear wave elastography (pSWE) for liver fibrosis in obese patients with metabolic dysfunction-associated steatotic liver disease (MASLD) using liver biopsy as the reference standard and to compare it with the FIB-4 index and aspartate to platelet ratio index (APRI).

Patients with obesity who met the diagnostic criteria for MASLD between April 2023 and December 2024 were selected for this retrospective single-centre study. Liver stiffness measurements were reported as median values of measurements, and Auto-pSWVs (m/s) were measured using the multisample pSWE technique. The diagnostic performance of auto shear wave velocities (Auto-pSWVs), FIB-4 index and APRI for significant fibrosis (≥F2) and advanced fibrosis (≥F3) of the liver was evaluated and compared using receiver operating characteristic curves with liver biopsy as the criterion. The correlation between Auto-pSWVs and the clinical variables of the subjects was evaluated.

Data from 241 patients were analysed. Auto-pSWVs were positively correlated with the pathological diagnosis of liver fibrosis (r=0.34, p<0.001), and the liver fibrosis stage was an independent risk factor for Auto-pSWVs (beta coefficient: 0.42, p< 0.001). In addition, Auto-pSWVs was superior to FIB-4 index and APRI when comparing the diagnostic performance of significant liver fibrosis (≥F 2) and advanced fibrosis (≥F3) (p < 0.05). The AUC of Auto-pSWVs was 0.75 (95% CI 0.66-0.85) and 0.96 (95% CI 0.89-1.0) in the ≥ F2 and ≥ F3 groups, respectively. The cut-off value for Auto-pSWVs were determined as follows: grade F2 ≥ 1.02 m/s; and grade F3 ≥ 1.30 m/s.

Multisample pSWE appears to be a valuable tool for the diagnosis of liver fibrosis in obese patients with MASLD.

Background/Objectives: Bariatric surgery (BS), drugs approved for type-2-diabetes (T2D), obesity, and liver fibrosis (resmetirom) announce the widespread use of fibrosis tests in patients with metabolic liver disease (MASLD). An unmet need is to reduce the uncertainty of biomarkers for the diagnosis of the early stage of clinically significant fibrosis (eF). This can be achieved if three essential but neglected STARD methods (3M) are used, which have a more sensitive histological score than the standard comparator (five-tiers), the weighted area under the characteristic curve (wAUROC) instead of the binary AUROC, and biopsy length. We applied 3M to FibroTest-T2D to demonstrate this reduction of uncertainty and constructed proxies predicting eF in large populations. Methods: For uncertainty, seven subsets were analyzed, four included biopsies (n = 1903), and to assess eF incidence, three MASLD-populations (n = 299,098). FibroTest-T2D classification rates after BS and in outpatients-T2D (n = 402) were compared with and without 3M. In MASLD, trajectories of proxies and incidence against confounding factors used hazard ratios. Results: After BS (110 biopsies), reversal of eF was observed in 16/29 patients (84%) using seven-tier scores vs. 3/20 patients (47%) using five-tier scores (p = 0.005). When the biopsy length was above the median, FibroTest-T2D wAUROC was 0.90 (SD = 0.01), and the wAUROC was 0.88 (SD = 0.1) when the length was below the median (p < 0.001). For the first time, obesity was associated with eF before T2D (p < 0.001), and perimenopausal age with apoA1 and haptoglobin increases (p < 0.0001). Conclusions: Validations of circulating biomarkers need to assess their uncertainty. FibroTest-T2D predicts fibrosis regression after BS. Applying 3M and adjustments could avoid misinterpretations in MASLD surveillance.

On-site conservative estimations of steatosis could result in the unnecessary discard of donor livers. This study applied the body mass index as an independent statistical indicator to determine the extent of this problem. We aimed to quantitatively evaluate if decisions based nonbiopsy donor liver assessments are more conservative (inclined to reject marginal fatty livers) than biopsy-based evaluations.

The study processed intradatabase comparisons using 177 081 datasets from Organ Procurement and Transplantation Network spanning 2004 to 2022 September in the United States. Postmatching body mass index was applied as an independent indicator of statistical risk of hepatic steatosis (HS).

A total of 7420, 4990, 5994, and 7523 pair of donors with/without biopsy records were matched in 2004-2010, 2011-2014, 2015-2018, and 2019-2022 September, respectively. Consistent with our hypothesis, absent biopsies and evaluations before and during organ procurement were observed to be more conservative, leading to the discard of 16.4% (2004-2010), 16.9% (2011-2014), 10.6% (2015-2018), and 10.3% (2019-2022 September) of potential donor livers.

The study concludes that there was a significant (10.3%-16.9%) disparity caused by on-site nonbiopsy assessments of HS, leading to the unnecessary discard of potential donor livers. The findings emphasize the need to develop more accurate intraoperative techniques for assessing HS to optimize donor liver procurement.

Cardiovascular disease and metabolic dysfunction-associated steatotic liver disease are common conditions associated with high mortality and morbidity, yet opportunities for integrated prevention are underinvestigated. We explored the association between impairment in the liver (defined by increased iron-corrected T1 (cT1) time) and/or heart (reduced left ventricular ejection fraction ≤ 50) and risk of experiencing cardiovascular- or liver-related events or all-cause mortality among 28,841 UK Biobank participants who underwent magnetic resonance imaging. Using Cox proportional hazard models, adjusted for age, sex, body mass index, type 2 diabetes and dyslipidaemia, we observed that cardiac impairment was associated with increased incidence of cardiovascular events (hazard ratio (HR) 2.3 (1.9-2.7)) and hospitalization (HR 2.1 (1.8-2.4)). Liver impairment was associated with incident cardiovascular hospitalization (cT1 ≥ 800 ms, HR 1.3 (1.1-1.5)), liver events (cT1 ≥ 875 ms, HR 9.2 (3.2-26) and hospitalization (cT1 ≥ 875 ms, HR 5.5 (3.2-9.3). Associations between cT1 and liver events were maintained in participants with metabolic dysfunction-associated steatotic liver disease (N = 6,223). Reduced left ventricular ejection fraction (≤50) combined with elevated cT1 (≥800 ms) were associated with earlier cardiovascular events (time to event 0.8 versus 2.4 years; P < 0.05). Cardiac and liver impairment are independently, or in combination, associated with cardiovascular or liver events, suggesting a dual role for magnetic resonance imaging in integrated prevention pathways.

Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in MASLD.

This cross-sectional study included prospectively recruited adults with MASLD aged 18-70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13. A genetic risk score (GRS) was calculated as the sum of established risk alleles in PNPLA3 minus protective variants in HSD17B13 (0=low risk, 1=high risk). We also estimated the polygenic risk score-hepatic fat content (PRS-HFC) and the adjusted version (PRS-5). The primary endpoint was the age-related change in liver stiffness measurement (LSM) on MRE by GRS. Findings were validated using an external cohort from Latin America.

Among 570 participants, the median age was 57 [49-64] years, 56.8% were women, and 34.2% were Hispanic. Median MRE was 2.4 [2.1-3.0] kPa, and 51% had high GRS. High GRS was independently associated with increased LSM (β=0.28 kPa, 95%CI:0.12-0.44, p=0.001) per 10-year age increase, while the low GRS group showed no significant difference. Similar findings were observed using PRS-HFC and PRS-5. PNPLA3 genotype alone also predicted higher LSM (C/G: β=0.32 kPa, 95%CI:0.02-0.61, p=0.034; G/G: β=0.87 kPa, 95%CI:0.52-1.22, p<0.0001) and G/G genotype was associated with significantly higher LSM by age 44, which was consistent in the validation population.

GRS, PRS-HFC, PRS-5, and PNPLA3 genotypes alone are associated with greater fibrosis per decade, resulting in divergent disease trajectories starting in midlife. Assessing genetic risk in MASLD will identify high-risk patients who require more frequent monitoring.

This study provides granular evidence that genetic predisposition, particularly the PNPLA3 G/G genotype, significantly influences the trajectory of liver fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), with a more pronounced impact emerging after the fourth decade of life. These findings highlight the importance of incorporating genetic risk assessment into MASLD management, as it allows for the early identification of high-risk individuals who may benefit from more frequent monitoring and targeted interventions. Given the rising global burden of MASLD, clinicians, researchers, and policymakers should consider integrating genetic stratification into existing risk assessment frameworks to refine screening and surveillance strategies. By optimizing patient selection for non-invasive fibrosis assessment and potential therapeutic interventions, this approach could enhance precision medicine efforts and may improve long-term outcomes.

This study compared the diagnostic performance of two attenuation imaging (ATI) modes-low-frequency (3 MHz) and high-frequency (4 MHz)-for assessing hepatic steatosis, with histopathological hepatic fat fraction (HFF) as the reference standard.

This prospective single-center study enrolled participants with suspected metabolic dysfunction-associated steatotic liver disease (MASLD) scheduled for liver biopsy or surgery between June 2023 and June 2024. Attenuation coefficient (AC) values were consecutively measured using low- and high-frequency ATI modes, while the skin-to-region of interest distance (SRD) was measured simultaneously. Spearman correlation analysis evaluated the relationships of AC with HFF and SRD, and linear regression identified factors affecting AC. Diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUROC).

In total, 119 participants (mean age, 37.2±12.0 years; 87 men) were included, with 73 (61.3%) diagnosed with MASLD. HFF ranged from 0% to 50%. The AC values in the lowfrequency mode were significantly higher than those in the high-frequency mode (0.61 vs. 0.54 dB/cm/MHz, P<0.001). HFF significantly influenced AC in both modes, whereas SRD affected AC only in the high-frequency mode (P<0.001). AC correlated positively with HFF in both modes (rs≥0.514, P<0.001) and negatively with SRD in the high-frequency mode (rs=-0.338, P<0.001). The AUROC for hepatic steatosis did not differ significantly between the two modes (0.751 vs. 0.771, P=0.609).

The low-frequency mode produced higher AC values than the high-frequency mode and demonstrated comparable diagnostic accuracy for assessing hepatic steatosis. Unlike the high-frequency mode, the low-frequency mode was not influenced by SRD.

There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study.

This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart. LSM progression and regression were defined by a ≥20% increase and an upward or downward change, respectively, in the LSM category in the Baveno VII categories for compensated advanced chronic liver disease, compared between participants with T2DM (n = 680) versus no T2DM (n = 551) at baseline. The mean (±SD) age and body mass index were 51.8 (±12.0) years and 34.0 (±6.5) kg/m 2 , respectively. The median (IQR) time between the first and last VCTE measurements was 4.1 (2.5-6.5) years. Participants with T2DM had higher LSM progression at 4 years (12% vs. 10%), 6 years (23% vs. 16%), and 8 years (50% vs. 39%), p = 0.04. Using a multivariable Cox proportional hazards model adjusted for multiple confounders, the presence of T2DM remained an independent predictor of LSM progression (adjusted HR: 1.35, 95% CI: 1.01-1.81, p = 0.04). T2DM was not associated with LSM regression ( p = 0.71). Mean HbA1c was significantly associated with LSM progression ( p = 0.003) and regression ( p = 0.02).

Using serial VCTE data from a multicenter study of participants with biopsy-proven metabolic dysfunction-associated steatotic liver disease, we demonstrate that T2DM and HbA1c are associated with LSM progression.

Conventional histopathological evaluation of liver biopsy slides has been invaluable in assessing the causes of liver injury, the severity of the underlying disease processes, and the degree of resulting fibrosis. However, the use of conventional histologic assessments as endpoints in clinical trials is limited by the reliability of scoring systems, variability in interpretation of histologic features and translation of continuous variables into categorical scores. To increase the precision and reproducibility of liver biopsy assessment, several artificial intelligence/machine learning (AI/ML) approaches have been developed to analyse high resolution digital images of liver biopsy specimens. Multiple AI/ML platforms are in development with promising results in post-hoc analyses of clinical trial biopsies. One such technique employs images generated by Second Harmonic Generation/Two Photon Excitation (SHG/TPE) microscopy that uniquely uses unstained liver biopsies to provide high resolution images of collagen fibres to assess and quantify collagen morphometry, and avoid challenges related to staining variability. One SHG/TPE microscopy methodology coupled with AI/ML based analysis, qFibrosis™, has been used post-hoc as an exploratory endpoint in several clinical trials for metabolic dysfunction-associated steatohepatitis (MASH) demonstrating its ability to provide a consistent and more nuanced assessment of liver fibrosis that still correlates well with traditional staging. This review summarizes the development of qFibrosis and outlines the need for additional studies to validate it as a sensitive marker for changes in fibrosis in the context of treatment trials and correlate these changes with subsequent liver-related outcomes.

Liver corrected T1 (cT1), measured with multiparametric magnetic resonance imaging, offers an alternative to liver biopsy to monitor treatment response and liver disease activity. We aimed to perform a systematic evaluation of change in cT1 following a treatment intervention in adults with metabolic dysfunction-associated steatotic liver disease (MASLD).

We searched the Cochrane Library, PubMed Central, and MEDLINE from 2014 to September 2024 for studies that examined cT1 responses following intervention in metabolic dysfunction-associated liver disease. Two authors independently screened records, assessed risk of bias, and extracted data. Meta-analyses were performed to explore the mean change in cT1 between baseline and end of study.

A total of 16 studies (n = 1134 individuals) were analyzed (13 randomized controlled trials [n = 1077]) and 3 prospective diet, lifestyle and bariatric surgery studies [n = 57]). The mean change in cT1 was -57 ms (95% confidence interval [CI], -62 to -52 ms) over a median 17 weeks (interquartile range: 12-24 weeks). By treatment type, fibroblast growth factor analogues, glucagon-like peptide-1 receptor agonists, and farnesoid X receptor agonists, cT1 had a mean change of -79 ms (95% CI, -90 to -68 ms) to -68 ms (95% CI, -77 to -58 ms) and -62 ms (95% CI, -74 to -49 ms), respectively. In contrast, the placebo arms showed a mean change in cT1 of 0 ms (95% CI, -8 to 8 ms).

Evidence to date supports a significant treatment-induced reduction in cT1 as compared with minimal changes in the placebo group. Our findings could inform study designs for investigational therapies and support monitoring of treatment response in individuals with metabolic dysfunction-associated liver disease in clinical trials and clinical practice.

Proton density fat fraction (PDFF) and R2* are noninvasive MRI biomarkers for quantifying fat and iron in abdominal organs. While 3.0 T MRI is widely used clinically, 5.0 T may offer improved accuracy and reliability. With the increasing availability of 5.0 T, assessing its feasibility and utility for quantifying PDFF and R2* in abdominal organs is needed.

To determine the agreement of the PDFF and R2* in the liver, pancreas, kidney, and paraspinal muscle at 2 different field strengths.

Prospective.

A total of 127 participants, including 60 healthy volunteers and 67 with metabolic dysfunction-associated steatotic liver disease (100 women and 27 men, 52 ± 9 years old).

3.0 T and 5.0 T; Chemical shift-encoded multi-echo gradient echo sequence.

PDFF and R2* values in the liver, pancreas, kidney, and paraspinal muscle were measured by three observers to evaluate the interobserver and interfield agreement using two 3.0 T scanners (scanner 1 and scanner 2) and one 5.0 T scanner.

Linear regression, Bland-Altman analyses, and intraclass correlation coefficients (ICCs). The p-value < 0.05 indicated statistically significant.

PDFF and R2* at 5.0 T were strongly correlated with those at two 3.0 T scanners for all organs (R2 = 0.905-0.998 for PDFF; 0.831-0.991 for R2*), indicating high interfield ICCs (0.892-0.993 for PDFF; 0.910-0.981 for R2*). Comparisons between 5.0 T and two 3.0 T scanners showed good interfield agreement for PDFF (mean bias, -0.57% to 0.03%) while a higher bias for R2* (mean bias, -16.53 to -2.64 s-1, 95% LoA, -34.28 to 1.21 s-1) at 5.0 T compared to the comparison between 3T scanners.

5.0 T revealed high interfield agreement between the PDFF and R2* with 3.0 T, which could provide reliable quantification of fat and iron contents in abdominal organs.

2.

Stage 2.

The diagnosis of liver fibrosis is critical in managing chronic liver diseases. The EASL guidelines now recognize ultrasound elastography as a valuable, non-invasive method for assessing liver fibrosis. However, there is a lack of uniform use and reporting of the technique. The purpose of this position paper was to provide guidance on using ultrasound elastography techniques and interpreting results in clinical practice.

A French national consensus panel of experts in radiology and hepatology, convened by SIAD (Société d'Imagerie Abdominale et Digestive) and AFEF (Association Française pour l'Etude du Foie), developed a position statement paper on best practices in ultrasound elastography. They were established using an online Delphi methodology that included an online panel discussion and item preparation. Consensus was achieved when ≥ 80 % of the participants agreed with a specific recommendation.

The accuracy and reliability of ultrasound elastography results could be significantly affected by a variety of operator-related and patient-related factors. Standard recommendations have been established in two areas, including recommendations for measurements and factors affecting results and reliability, and guidelines for standardized reporting of ultrasound elastography results.

This position paper is a comprehensive and accessible guide for clinicians that outlines best practices and standardized protocols to improve the reliability of ultrasound elastography assessments.

Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health challenge, with evidence indicating that hepatic inflammation and fibrosis are heterogeneous processes. Purpose To measure liver mechanical property heterogeneity using MR elastography (MRE) and evaluate its potential as a biomarker for tissue inflammation and fibrosis in patients with MASLD. Materials and Methods Mechanical tissue heterogeneity in MASLD was assessed at three-dimensional vector MRE pixel-wise histogram analysis of shear stiffness and loss modulus in preclinical and clinical studies. The preclinical study involved 25 rats that were examined monthly, whereas the clinical study analyzed data from 179 participants across two prospective studies (September 2015 to November 2022), including some who underwent bariatric surgery at pretreatment and posttreatment MRE examinations. Mean and coefficient of variation (CV) of shear stiffness and loss modulus were calculated for each examination. Nonparametric tests and Spearman correlation coefficient were used to compare MRE-derived tissue mechanics with biopsy-confirmed fibrosis and inflammation and assess correlations with portal pressure and histopathologic hepatic fibrosis. Results The preclinical study showed that, in cirrhotic livers, CV of loss modulus positively correlated with portal pressure and fibrosis area ratio variation (ρ = 0.52 [P = .008] and 0.55 [P = .005], respectively). The clinical study showed that, in 10 healthy volunteers (median age, 36.5 years; IQR, 34.0-38.8 years; five females) and 169 participants with MASLD (median age, 50.1 years; IQR, 41.0-58.2 years; 118 females), CV of sheer stiffness (from 0.12 to 0.30 in healthy participants to participants with stage 4 fibrosis) and loss modulus (from 0.31 to 0.51 in healthy participants to participants with grade 3 inflammation) increased with increasing severity of fibrosis and inflammation, respectively. In 36 participants who underwent bariatric surgery, the CV of sheer stiffness decreased at the 1-year follow-up, from 0.16 (IQR, 0.14-0.18) to 0.14 (IQR, 0.12-0.16) (P = .009). Conclusion Tissue mechanical heterogeneity assessed at MRE positively correlated with progression of MASLD, demonstrating potential as a biomarker for liver disease severity and therapeutic intervention. ClinicalTrials.gov Identifier: NCT02565446 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Moura Cunha in this issue.

The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD.

This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed.

Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4.

The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly common, especially among obese individuals. This study evaluated the liver/spleen Hounsfield unit (HU) ratio (L/S ratio) as an indicator of steatosis and related metabolic diseases using contrast-enhanced computed tomography (CT).

A retrospective analysis was conducted on 34 patients who underwent bariatric surgery at Eunpyeong St. Mary's Hospital between March 2019 and July 2023. All patients underwent CT scans before and 6 months after surgery. The L/S ratio was calculated by dividing the average value of 3 HU of the liver by that of the spleen. The ratio correlated with pre- and post-surgery weight changes, comorbidities, and laboratory findings.

The mean preoperative body mass index (BMI) was 40.5. Post-surgery, BMI significantly decreased to 31.5, and the number of patients with diabetes reduced from 18 (52.9%) to 4 (11.8%). Significant reductions were observed in hemoglobin A1c (HbA1c), aspartate transaminase (AST), and alanine transaminase (ALT) levels after surgery. The L/S ratio increased from 0.7±0.2 to 0.9±0.1, correlating with liver function improvements and weight loss (all with P<0.001). Patients with a larger change in L/S ratio demonstrated more significant improvements in AST, ALT, and HbA1c levels and a higher total weight loss percentage.

This study demonstrated a strong correlation between changes in the L/S ratio and metabolic improvements, including diabetes remission, following bariatric surgery. The L/S ratio could serve as a valuable index for assessing NAFLD severity and monitoring the outcomes in patients undergoing bariatric surgery.

There are no FDA-approved therapies for alcohol-associated liver disease (ALD). Preclinical studies indicate that blocking IL-23/IL-17 signalling may reverse liver injury. Guselkumab, an IL-23-specific antibody approved for psoriasis, may be beneficial for ALD.

We aimed to assess the safety and tolerability of guselkumab in patients with ALD.

This phase-1 dose-escalation study included patients with ≥ 2 DSM-5 criteria for alcohol use disorder, significant steatosis (MRI-PDFF ≥ 8%) and MRE < 3.63 kPa (to exclude advanced disease). Guselkumab was given subcutaneously on Days 1 and 29 in 30, 70 or 100 mg dose cohorts. Primary endpoints were adverse events (AEs) and dose-limiting toxicity.

We enrolled 13 patients (three 30 mg, three 70 mg, and seven 100 mg). Eleven completed the study and two early discontinued in the 100 mg group. Of them, 77% were men, and the median age was 53 [IQR 49-61] years. The median MRI-PDFF and MRE were 18.4% [IQR 8.4%-34.0%] and 2.5 [2.2-2.6] kPa, respectively. The most frequent AEs were hyperuricemia (13%, mild only) and elevated lipase (11%, mild and moderate). There were no serious adverse events or significant variations in liver enzymes. There was a suppression of peripheral interleukin (IL)-17, IL-23, IL-1b and TNF-α in the 70 and 100 mg groups, and a significant decrease in alcohol consumption over time (AUDIT-C: 6 [3-7] vs. 5 [1-6], p = 0.023).

Guselkumab is safe in doses up to 100 mg and may reduce inflammation markers in ALD. These findings support further phase 2 studies to evaluate the efficacy of guselkumab in ALD, particularly in patients with severe phenotypes.

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

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

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

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

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

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

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

Background Early diagnosis of liver cirrhosis in patients with chronic liver disease (CLD) can help delay/prevent complications and thereby improve survival. The currently available diagnostic modalities for the non-invasive assessment of hepatic fibrosis, especially FibroScan, are costly and not widely available, whereas various non-invasive scores for the assessment of fibrosis are cumbersome. Hence, we aimed to develop an easy and simple score for predicting cirrhosis in patients from Eastern India suffering from CLD with a better diagnostic accuracy. Methodology This cross-sectional, observational study was conducted between September 2019 and September 2021 in East India. Our study participants were patients who had CLD of etiologies such as alcohol-related liver disease, non-alcoholic fatty liver disease, chronic viral hepatitis B, chronic viral hepatitis C, primary biliary cholangitis, and autoimmune hepatitis, who had undergone FibroScan of the liver. All demographic details were noted, and the patients were subjected to physical examination, followed by hematological as well as biochemical investigations, including liver function tests. Non-invasive scores (such as aspartate aminotransferase (AST) to platelet ratio index (APRI) and Fibrosis-4 score (FIB-4) and red cell distribution width (RDW) to platelet ratio (RPR)) were computed, and their diagnostic accuracy for prediction of advanced fibrosis and cirrhosis were evaluated by receiver operating characteristic curve (ROC curve) analysis with comparison of area under the ROC curves. Pearson correlation and logistic regression analysis were also performed to study the association of these scores with advanced fibrosis and cirrhosis. Results The area under the ROC (AUROC) curve of the APRI score, FIB-4 score, RPR, and RPR × AST for prediction of advanced liver fibrosis was 0.817, 0.799, 0.706, and 0.811, respectively. Similarly, the AUROC of the above scores for the prediction of cirrhosis was 0.889, 0.858, 0.797, and 0.898. However, the product of RPR and AST was superior than APRI and FIB-4 for predicting cirrhosis. An RPR × AST value above the cut-off of 4.818 can help predict liver cirrhosis with 85.7% sensitivity and 85.5% specificity. Pearson correlation and logistic regression analysis also proved the association of these scores with liver fibrosis. Conclusions RPR is a simple, inexpensive, and easily available marker for predicting liver cirrhosis. Nevertheless, the variable RPR × AST can predict liver cirrhosis in patients with CLD with even greater diagnostic accuracy.

The need for early non-invasive diagnostic tools for chronic liver fibrosis is growing, particularly in individuals with obesity, non-alcoholic fatty liver disease (NAFLD), and the metabolic syndrome (MetS) since prevalence of these conditions is increasing. This case-control study compared non-invasive liver fibrosis markers in obesity with NAFLD and MetS (NAFLD-MetS, n = 33), in obese (n = 28) and lean (n = 27) control groups. We used MRI (T1 relaxation times (T1) and liver stiffness), circulating biomarkers (CK18, PIIINP, and TIMP1), and algorithms (FIB-4 index, Forns score, FNI, and MACK3 score) to assess their potential in predicting liver fibrosis risk. We found that T1 (892 ± 81 ms vs. 818 ± 64 ms, p < 0.001), FNI (15 ± 12% vs. 9 ± 7%, p = 0.018), CK18 (166 ± 110 U/L vs. 113 ± 41 U/L, p = 0.019), and MACK3 (0.18 ± 0.15 vs. 0.05 ± 0.04, p < 0.001) were higher in the NAFLD-MetS group compared with the obese control group. Moreover, correlations were found between CK18 and FNI (r = 0.69, p < 0.001), CK18 and T1 (r = 0.41, p < 0.001), FNI and T1 (r = 0.33, p = 0.006), MACK3 and FNI (r = 0.79, p < 0.001), and MACK3 and T1 (r = 0.50, p < 0.001). We show that liver fibrosis markers are increased in obese individuals with NAFLD and MetS without clinical signs of liver fibrosis. More studies are needed to validate the use of these non-invasive biomarkers for early identification of liver fibrosis risk.

Noninvasive detection of liver steatosis and monitoring its progression are essential for effective therapeutic management. We validated the diagnostic performance of an ultrasonography (US)-based steatotic liver scoring system, derived from the B-mode method and the hepatic steatosis index (HSI) for the detection of liver steatosis, as identified by proton density fat fraction (PDFF) measurements on magnetic resonance imaging (MRI).

A total of 916 patients with chronic liver disease were included in the analysis.

The median MRI-PDFF value was 4.0% (interquartile range: 2.0-9.7). The distribution of scores (0/1/2/3/4/5/6) according to the US-based steatotic liver scoring system was as follows: 475, 36, 99, 78, 141, 66, and 21, respectively. The median HSI was 32.8 (28.9-37.4). A significant positive association between advancing scores of the US-based steatotic liver scoring system and increasing MRI-PDFF values was observed (p < 0.001). The diagnostic performance of the US-based steatotic liver scoring system and HSI for detecting steatosis grades ≥1, ≥2, and 3, as determined by MRI-PDFF, showed areas under the receiver operating characteristic curve of 0.940 and 0.842 (p < 0.001), 0.949 and 0.847 (p < 0.001), and 0.945 and 0.864 (p < 0.001), respectively. When the cutoff values of the scoring system were set at 2, 3, and 4 for steatosis grades ≥1, ≥2, and 3, the sensitivity and specificity were 90.6% and 90.5%, 92.9% and 83.0%, and 93.3% and 84.0%, respectively.

The B-mode US-based steatotic liver scoring system demonstrated robust diagnostic capability in detecting liver steatosis.

Lanifibranor, a pan-peroxisome proliferator-activated receptor agonist, has demonstrated therapeutic efficacy on metabolic dysfunction-associated steatohepatitis (MASH) resolution and fibrosis improvement in the Phase IIb NATIVE study. The histologic endpoints of MASH resolution and fibrosis improvement (E1), MASH resolution without worsening of fibrosis (E2), and fibrosis improvement without worsening of MASH (E3) were investigated with the aim of identifying biological signatures of E1, E2, and E3 responders based on serum biomarkers in patients treated with lanifibranor.

NATIVE evaluated lanifibranor 800 and 1200 mg daily vs placebo in patients with non-cirrhotic MASH treated over 24 weeks. Liver biopsy was obtained at baseline and the end of treatment. Patients receiving lanifibranor were pooled, and those with liver biopsies were selected (n = 142). A panel of 65 biomarkers were evaluated by assessing baseline and absolute as well as relative changes at the end of treatment.

The biomarkers included in E1 score (baseline adiponectin and ferritin; delta of matrix metalloproteinase 9 and transferrin), E2 score (baseline cytokeratin 18 Fragment M65; delta of hyaluronic acid, fructosamine, and alanine aminotransferase), and E3 score (baseline cytokeratin 18 Fragment M65 and gamma-glutamyl transferase; delta of aspartate aminotransferase, insulin, and urea) represented metabolic, apoptotic, and fibrosis aspects of the disease. These signatures provided good accuracy for the noninvasive identification of histologic response under lanifibranor with area under the receiver operating characteristic curve at 0.81 ± 0.08 for E1 score, 0.80 ± 0.08 for E2 score, and 0.81 ± 0.08 for E3 score.

Results from this analysis show evidence that baseline values and changes in selected serum biomarkers can aid in predicting histologic response in MASH under lanifibranor treatment. These findings support utilizing a similar approach in a larger sample size (NATiV3, NCT03008070).

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.

MRI biomarkers of liver disease are robust and reproducible alternatives to liver biopsy. Emerging data suggest that absolute reduction in iron-corrected T1 (cT1) of ≥80 ms and relative reduction in liver fat content (LFC) of 30% reflect histological improvement. We aimed to validate the associations of changes to these non-invasive biomarkers with histological improvement, specifically the resolution of steatohepatitis.

We performed a retrospective analysis of participants from three interventional clinical trials who underwent multiparametric MRI to measure liver cT1 and LFC (LiverMultiScan) alongside biopsies at baseline and end of study. Responders were defined as those achieving resolution of steatohepatitis with no worsening in fibrosis. Differences in the magnitude of change in cT1 and LFC between responders and non-responders were assessed.

Individual patient data from 150 participants were included. There was a significant decrease in liver cT1 (-119 ms vs. -49 ms) and LFC (-65% vs. -29%) in responders compared to non-responders (p <0.001), respectively. The diagnostic accuracy to identify responders was 0.72 (AUC) for both. The Youden's index for cT1 to separate responders from non-responders was -82 ms and for liver fat was a 58% relative reduction. Those achieving a ≥80 ms reduction in cT1 were 5-fold more likely to achieve histological response (sensitivity 0.68; specificity 0.70). Those achieving a 30% relative reduction in liver fat were ∼4-fold more likely to achieve a histological response (sensitivity 0.77; specificity 0.53).

These results, from a pooled analysis of three drug trials, demonstrate that changes in multiparametric MRI markers of liver health (cT1 and LFC) can predict histological response for steatohepatitis following therapeutic intervention.

We investigated the utility of two MRI-derived non-invasive tests, iron-corrected T1 mapping (cT1) and liver fat content from proton density fat fraction (PDFF), to predict histological improvement in patients who had undergone experimental treatment for metabolic dysfunction-associated steatohepatitis. Using data from 150 people who participated in one of three clinical trials, we observed that a reduction in cT1 by over 80 ms and a relative reduction in PDFF of over 58% were the optimal thresholds for change that predicted resolution of steatohepatitis on histology. PDFF as a marker of liver fat, and cT1 as a specific measure of liver disease activity, are both effective at identifying those who are likely responding to drug interventions and experiencing improvements in overall liver health.

NCT02443116, NCT03976401, NCT03551522.

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.

Endoscopic ultrasound shear wave elastography (EUS-SWE) is a novel modality for liver stiffness measurement. The aims of this study are to evaluate the performance and reliability of EUS-SWE for detecting advanced liver disease in a prospective cohort.

EUS-SWE measurements were prospectively obtained from patients undergoing EUS between August 2020 and March 2023. Liver stiffness measurements were compared between patients with and without advanced liver disease (ALD), defined as stage ≥3, to determine diagnostic accuracy for advanced fibrosis and portal hypertension. Logistic regression was performed to identify variables that impact the reliability of EUS-SWE readings. Select patients underwent paired magnetic resonance elastography (MRE) for liver fibrosis correlation.

Patients with ALD demonstrated higher liver stiffness compared to healthy controls (left lobe: 17.6 vs. 12.7 kPa, P <0.001; median right lobe: 24.8 vs. 11.0 kPa, P <0.001). The area under the receiver operator characteristic (AUROC) for the detection of ALD was 0.73 and 0.80 for left and right lobe measurements, respectively. General anesthesia was associated with reliable EUS-SWE liver readings (odds ratio: 2.73, 95% CI: 1.07-7.39, P =0.040). Left lobe measurements correlated significantly with MRE with an increase of 0.11 kPa (95% CI: 0.05-0.17 kPA) for every 1 kPa increase on EUS-SWE. D.

SWE is a promising technology that can readily be incorporated into standard EUS examinations for the assessment of ALD.

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.

Exercise is a key component of lifestyle management in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but neither its therapeutic effect on the active stage of the disease, that is metabolic dysfunction-associated steatohepatitis (MASH) nor the mediating mechanisms have been characterized. Therefore, we performed multi-omic phenotyping of patients with MASLD-MASH on an exercise program.

Fifteen patients with MASLD conducted high-intensity interval training (HIIT) combined with home-based training for 12 weeks. MASLD was evaluated using histology, transient elastography, and multiparametric magnetic resonance imaging (MRI) before and after the intervention. Change in maximal oxygen consumption (VO2max) and MRI-determined liver fat were compared with a control group of patients with MASLD (n = 22). RNA sequencing was performed on liver, muscle, and fat biopsies of patients in the exercise group. Stool was analyzed by shotgun metagenomics and untargeted metabolomics was performed on plasma, urine, adipose, and stool.

HIIT increased VO2max by 10.1% and improved mitochondrial metabolism in skeletal muscle, indicating improved cardiorespiratory fitness and adherence. VO2max increased significantly in the exercise group compared with controls. Histologically, no reduction in steatosis, MASH, or liver fibrosis was observed; however, transient elastography tended to improve. MRI-determined liver fat did not change in the exercise group compared with controls. HIIT induced changes in mRNA expression of genes related to beiging of adipose tissue and fibrogenesis in liver. In addition, specific gut microbial taxa and metabolites changed.

HIIT increased cardiorespiratory fitness and induced beneficial gene expression changes in muscle, adipose tissue, and liver, but without translation into histological improvement of MASLD. Longer exercise intervention trials are warranted to validate or refute current recommendations for exercise as a cornerstone treatment for MASLD-MASH.

Despite exercise being considered as a key component of lifestyle management for steatotic liver disease, neither the clinical effects nor the mechanisms involved are completely understood. We show that a high-intensity interval training (HIIT) program in 15 patients with metabolic dysfunction-associated steatotic liver disease (MASLD) improved cardiorespiratory fitness, compared with 22 control patients with MASLD who did not participate in an exercise program, however, it did not improve MASLD. HIIT induced a positive effect on fat tissue and muscle metabolism which was accompanied with changes in certain gut bacteria and metabolites in blood and urine. These findings improve our understanding of the effects of exercise on the whole-body metabolism in relation to steatotic liver disease. As such, this study provides a basis for future exercise interventions in patients with MASLD, required to thoroughly test current guideline advice for exercise as a cornerstone treatment for MASLD of all stages.

Dutch Trial Register (registration number NL7932).

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

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

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

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

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one-third of adults globally. Despite efforts to develop non-invasive diagnostic tools, liver biopsy remains the gold standard for diagnosing metabolic dysfunction-associated steatohepatitis (MASH) and assessing fibrosis. This study investigated RNA aptamer panels, selected using APTASHAPE technology, for non-invasive MASLD diagnosis and fibrosis stratification. Aptamer panels were selected in a cohort of individuals with MASLD (development cohort, n = 77) and tested in separate cohorts: one with MASLD (test cohort, n = 57) and one assessed for bariatric surgery (bariatric cohort, n = 62). A panel distinguishing MASLD without steatohepatitis from MASH accurately stratified individuals in the developmentcohort (AUC = 0.83) but failed in the test and bariatric cohorts. It did, however, distinguish healthy controls from individuals with MASLD, achieving an AUC of 0.72 in the test cohort. A panel for fibrosis stratification differentiated F0 from F3-4 fibrosis in the development cohort (AUC = 0.68) but not in other cohorts. Mass spectrometry identified five plasma proteins as potential targets of the discriminative aptamers, with complement factor H suggested as a novel MASLD biomarker. In conclusion, APTASHAPE shows promise as a non-invasive tool for diagnosing and staging MASLD and identifying associated plasma biomarkers.

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.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and non-alcoholic fatty pancreatic disease (NAFPD) are metabolic diseases with rising incidence. Fatty infiltration may lead to dysfunction of the liver and pancreatic tissues. This study aims to quantify liver and pancreatic fat fractions and examine their correlation with disease severity in acute pancreatitis patients.

The severity of acute pancreatitis was assessed using the revised Atlanta classification (RAC), computed tomography severity index (CTSI), and modified CTSI (mCTSI). Proton density fat fraction (PDFF) levels of the liver and pancreas were measured via IDEAL MRI. Patients were categorized into biliary and non-biliary pancreatitis groups. Correlations between PDFF levels and the RAC, CTSI, and mCTSI scores were analyzed.

A total of 127 patients were included, with MASLD present in 40.9% and NAFPD in 30%. Liver PDFF values were significantly higher in non-biliary pancreatitis (p = 0.040). Patients with MASLD exhibited higher CTSI and mCTSI scores (p = 0.009, p = 0.033, respectively). No significant differences were observed in severity scales between patients with and without NAFPD. Liver PDFF was positively correlated with CTSI and mCTSI scores in biliary pancreatitis. ROC analysis identified a liver PDFF > 3.9% (p = 0.002) and pancreatic corpus PDFF > 12.1% (0.028) as diagnostic markers for severe pancreatitis. In addition, a liver PDFF < 4.5% (p = 0.042) was an indicator for biliary pancreatitis.

MASLD is associated with increased severity in acute pancreatitis. IDEAL MRI-derived PDFF levels of the liver and pancreas show potential in predicting severe acute pancreatitis and distinguishing between biliary and non-biliary etiologies.

While the associations between pediatric non-obese metabolic dysfunction-associated fatty liver disease (MAFLD) and multiple diagnostic biomarkers are well-established, the role of a broader range of blood-based, urine-based, and body composition-based biomarkers for monitoring MAFLD are needed.

A pediatric cohort was established in Wuxi, China. We measured body composition biomarkers, blood-based and urine-based biomarkers, and liver stiffness in participants to diagnose MAFLD and identify alternative and novel potential biomarkers for MAFLD. Body mass index (BMI), high-density lipoprotein cholesterol (HDLC), triglycerides, glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist perimeter were used as MAFLD diagnostic biomarkers. To identify alternative biomarkers, we performed correlation analysis to determine biomarkers exhibited strong correlation (|r| > 0.8, p-value < 0.05) with diagnostic biomarkers. To identify novel potential biomarkers, we performed regression analysis to determine biomarkers associated with MAFLD (p-value < 0.05 in stepwise multivariate regression) among the remaining biomarkers that are not related to the diagnostic biomarkers.

Out of 1,108 participants who completed all examinations (N biomarker = 91), 113 participants were diagnosed with MAFLD (prevalence: 14.99% in boys and 5.18% in girls). 27 biomarkers that were strongly correlated with diagnostic biomarkers were identified as alternative biomarkers. A multivariate logistic regression analysis identified 9 novel potential biomarkers including 5 blood-based biomarkers (plateletocrit, calcium, insulin, AST/ALT ratio, total bilirubin), urine pH, and body fat measurements in the arm, leg, and thigh.

This study illustrated the characteristics and potential alternative and novel biomarkers of MAFLD based on a Chinese paediatric cohort. These findings posed new paths in guiding the prevention and early diagnosis and prevention.

This trial was registered in the Chinese Clinical Trials Registry (ChiCTR2400080508). The date of first registration, 01/31/2024. Retrospectively registered.