This study examines the impact of glucosamine on the progression and outcomes of metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction and alcohol-associated liver disease (MetALD) using a large scale cohort.

Present study utilized inverse probability of treatment weighting (IPTW) to adjust for confounders in this cohort study. Participants were classified based on glucosamine use, and primary and secondary outcomes included all-cause mortality, liver cirrhosis, cardiovascular disease, cerebrovascular disease, and chronic kidney disease (CKD) incidences. Cox proportional hazards models were used to assess hazard ratios and 95 % confidence intervals.

We found that glucosamine significantly reduces all-cause mortality in MASLD and MetALD cohorts after IPTW adjustment (P < 0.001). Additionally, glucosamine use was associated with lower liver cirrhosis incidence in MASLD both before (P = 0.003) and after IPTW adjustment (P = 0.046). Glucosamine also decreased cardiovascular disease risk in MASLD (P < 0.001) and MetALD (P = 0.037) cohorts, though it showed no significant impact on cerebrovascular disease incidence. Furthermore, glucosamine use was associated with a significantly lower incidence of CKD in the MASLD cohort (P = 0.034) and the entire cohort (P = 0.030), but not in the No steatotic liver disease cohort or MetALD cohort.

The findings suggest that glucosamine could be a beneficial supplementary therapy for managing steatotic liver diseases, particularly for patients at high risk for cardiovascular and renal complications. Further clinical trials are required to validate these potential benefits.

Given the increasing prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH), there is a critical need for accurate non-invasive early diagnostic markers.

This study aimed to validate NLRP3-related RNA signatures (EP300, CPN60, and ITGB1 mRNAs, miR-6881-5p, and LncRNA-RABGAP1L-DT-206) using an integrated molecular approach and advanced machine-learning algorithms to identify robust biomarkers for early diagnosis of NASH.

A cohort of 237 participants (117 Healthy controls, 60 MAFLD, 120 NASH) was utilized. Twenty-five demographic, clinical, and molecular features were collected from each participant. Various machine learning models were trained on the dataset.

The Random Forest algorithm emerged as the most effective classifier. The model identified nine key features: EP300 mRNA, CPN60 mRNA, AST, D. bilirubin, Albumin, GGT, HbA1c, HOMA-IR, and BMI, achieving an impressive 97 % accuracy in distinguishing NASH from non-NASH cases.

The integration of molecular, clinical, and demographic data with machine learning algorithms provides a highly accurate method for the early diagnosis of NASH. This model holds promise for early detection in individuals at risk of progressing to cirrhosis or liver cancer and may aid in identifying new therapeutic targets for managing NASH.

The objective of this study was to validate the diagnostic accuracy of the acFibroMASH index in a population of metabolic dysfunction-associated steatotic liver disease (MASLD) patients with at-risk metabolic dysfunction-associated steatohepatitis (MASH) and to compare it with other scoring systems.

394 patients with biopsy-proven MASLD were retrospectively enrolled. The patients were divided into the at-risk MASH (NAFLD activity score ≥ 4 and significant fibrosis) group (n = 103) and the non-at-risk MASH group (n = 291). The diagnostic performance of the acFibroMASH index was compared to that of fibroScan-aspartate aminotransferase (FAST) and other noninvasive fibrosis scores by plotting the receiver operating characteristic curve (ROC), including the area under the curve (AUC), sensitivity, and specificity. Cut-offs of the acFibroMASH index for sensitivity (≥ 0.90) and specificity (≥ 0.90) were obtained in our cohort.

The AUC of the acFibroMASH index in assessing at-risk MASH was 0.780, while the AUC of FAST was 0.770. The comparison of acFibroMASH with FAST showed no significant difference (P = 0.542). When the cut-off value for acFibroMASH was < 0.15, 95.5% of at-risk MASH patients could be excluded in 89 patients correctly. Conversely, when the cut-off value was set at > 0.39, 49.3% of at-risk MASH patients could be diagnosed in 140 patients correctly. When the NPV was set at 0.900, the critical value for exclusion was determined to be 0.23, with a sensitivity of 0.835 and a specificity of 0.526.

This study validated the efficacy of the acFibroMASH index in predicting at-risk MASH in a population of MASLD patients, demonstrating comparable performance to that of the FAST. The acFibroMASH index may provide a valuable clinical basis for screening and identifying at-risk MASH in primary care settings.

To address the need for a simple model to predict ≥ F2 fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients, a study utilized data from 791 biopsy-proven MASLD patients from the NASH Clinical Research Network and Jinan University First Affiliated Hospital. The data were divided into training and internal testing sets through randomized stratified sampling. A multivariable logistic regression model using key categorical variables was developed to identify ≥ F2 fibrosis. External validation was performed using data from the FLINT trial and multiple centers in China. The DA-GAG score, incorporating diabetes, age, GGT, aspartate aminotransferase/ platelet ratio, and globulin/ total protein ratio, demonstrated superior performance in distinguishing ≥ F2 fibrosis with an area under the receiver operating characteristic curve of 0.79 in training and over 0.80 in testing datasets. The DA-GAG score efficiently identifies MASLD patients with ≥ F2 fibrosis, significantly reducing the medical burden.

Sodium-glucose co-transporter type-2 (SGLT2) inhibitors have been identified to have a crucial hepatoprotective role in patients with type 2 diabetes (T2DM) and metabolic-associated steatotic liver disease (MASLD). Thus, we aimed to assess the effect of SGLT2 inhibitors on hepatic steatosis in patients with T2DM and MASLD added to the standard of care (SOC) treatment. Our study was a single-arm clinical trial with trial no ISRCTN85961860. Thirty T2DM patients with MASLD were recruited from the outpatient endocrinology and diabetes clinic of the Internal Medicine Department at Kasr Al-Aini Hospital, Cairo University, Egypt. Our Patients received Empagliflozin 10 mg daily which was added to SOC treatment and followed up for 24 weeks. Magnetic resonance imaging proton density fat fraction (MRI-PDFF) was done at baseline and after 24 weeks to assess the percentage change in hepatic fat mass. Also changes in Fib-4 and NAFLD fibrosis scores were calculated. Our study showed a statistically significant decrease in the mean MRI-PDFF measurement of hepatic steatosis after 24 weeks of adding empagliflozin to SOC treatment (13.297 ± 7.15) compared to the mean at baseline (15.288 ± 8.72), P = 0.006 with overall percentage decrease about 13.16% of liver steatosis. There were significant decreases in BMI, fasting blood glucose, and Alanine transaminase, (P < 0.001, 0.03, 0.01) respectively. There were no significant differences in Fib-4 or NAFLD fibrosis scores. Adding empagliflozin 10 mg to the standard treatment in patients with diabetes and MASLD could reduce hepatic fat mass significantly after 24 weeks of treatment. Thus, adding SGLT2 inhibitors to the clinical practice guidelines could be a therapeutic agent for patients with MASLD and T2DM.

Background: Triglyceride glucose (TyG) and its related index (TyG-body mass index, TyG-BMI) are recognized as markers for nonalcoholic fatty liver disease (NAFLD), but their associations with metabolic dysfunction-associated steatotic liver disease (MASLD) and significant liver fibrosis (SLF) risk are less studied. Therefore, this study explores the effectiveness of these indices in assessing MASLD and SLF risk in the U.S. population. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional study involving 5520 participants from the general population was performed. This research measured demographic, anthropometric, biochemical, comorbid, and lifestyle characteristics, all of which are considered risk factors for MASLD/SLF. Results: Upon controlling for confounding variables, only the TyG-BMI was found to have a consistent positive association with the risk of MASLD and SLF. Specifically, for each standard deviation increase, the odds ratio (OR) and 95% confidence interval (CI) were 4.44 (3.64-9.26, p for trend < 0.001) for MASLD and 2.48 (2.15-2.87, p for trend < 0.001) for SLF. Significant interactions were identified among age, sex, and the risk of MASLD associated with the TyG-BMI. The TyG-BMI also had a significant threshold effect on the risk of MASLD at a cutoff point of 180.71. Furthermore, the area under the receiver operating characteristic curve (AUC) revealed that the TyG-BMI better predicted the risk of MASLD and SLF (AUC 0.820, 95% CI 0.810-0.831; AUC 0.729, 95% CI 0.703-0.756, respectively). In addition, the integrated discrimination improvement (IDI), decision curve analysis (DCA), and net reclassification index (NRI) also demonstrated the satisfactory predictive ability of the TyG-BMI. Conclusions: Within this large dataset, the TyG-BMI was independently associated with both the MASLD score and the SLF in the MASLD cohort. Its predictive efficacy consistently surpassed that of TyG and other noninvasive models, indicating that TyG-BMI has potential for the early identification of MASLD and SLF risk.

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

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.

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) often manifest a combination of cardiometabolic risk factors of varying severity. The cardiometabolic phenotypes and their associations with advanced liver fibrosis and all-cause mortality among patients with MASLD warrant further investigation.

A total of 4209 and 1901 eligible participants were obtained from the National Health and Nutrition Examination Survey and included in the original and replication datasets, respectively. In the original dataset, three distinct and stable cardiometabolic phenotypes were identified using unsupervised cluster analyses, including mild cardiometabolic risk factor (MCMRF) phenotype, overweight combined with high diastolic blood pressure dominated (OCHBP) phenotype, and severe glucose and lipid metabolic dysfunction dominated (SGLMD) phenotype. The above phenotypes were subsequently replicated in the replication dataset, demonstrating similar characteristics. After adjusting for potential covariates, the results of logistic and Cox regression models showed that OCHBP and SGLMD phenotypes were significantly associated with higher odds of advanced liver fibrosis (OCHBP: OR = 4.37, 95 % CI: 1.54-12.35, P = 0.020; SGLMD: OR = 9.66, 95 % CI: 4.76-19.61, P = 0.002) and an increased risk of all-cause mortality (OCHBP: HR = 1.39, 95 % CI: 1.17-1.65, P < 0.001; SGLMD: HR = 2.51, 95 % CI: 1.86-3.40, P < 0.001) compared to the MCMRF phenotype. Moreover, the observed associations remained statistically significant in most subgroups, and a series of sensitivity analyses further confirmed the robustness of these findings.

Three heterogeneous cardiometabolic phenotypes were identified among participants with MASLD, showing significant associations with two critical outcomes. These novel phenotypes may be of great importance to precision medicine in MASLD.

The liver function tests and noninvasive tests (NITs) play important roles in the follow-up and monitoring of fatty liver disease (FLD). Our aim is to establish annual biological variation (BV) and personalized reference intervals (prRIs) of liver function tests for the first time in order to accurately assess the status and progress of FLD.

67 fatty liver patients who participated in regular physical examination once a year for six consecutive years, were enrolled. Based on these patients, we calculated annual BV and derived parameters, including reference change value (RCV), index of individuality (II), and total variation around the true homeostatic set point (TVset) which could further be used to derive prRI.

We calculated the annual within-subject BV (CVI), within-person BV (CVP), RCV, II, TVset of 8 liver function tests and 3 NITs for fatty liver patients. CVI estimates of fatty liver patients for half of liver function tests were significantly lower than those of healthy people and these could lead to a lower RCV. IIs of all measurands were < 1.4 except for total bile acids (TBA). The mean of CVP is similar to the CVI; however, there is a significant heterogeneity in CVP among different subjects. Annual TVset estimates for 7 measurands were lower and prRI was also narrower in fatty liver patients than that of healthy people.

Annual BV and their derived parameters based on fatty liver patients can provide an objective basis for the monitoring and follow-up of FLD, a global epidemic disease.

The current subclassification of steatotic liver disease (SLD) relies on validated questionnaires, such as Alcohol Use Disorders Identification Test (AUDIT) and Lifetime Drinking History (LDH), which, while useful, are impractical and lack precision for their use in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity.

To assess the diagnostic accuracy of PEth for differentiating metabolic dysfunction and alcohol-associated liver disease (MetALD) from metabolic dysfunction-associated steatotic liver disease (MASLD) in a large, population-based, prospective, multiethnic cohort of individuals with overweight or obesity.

This is a cross-sectional analysis of a prospective study including 374 adults with overweight or obesity residing in Southern California who had SLD as defined by MRI-PDFF ≥ 5%. The clinical research visit included medical history, biochemical and PEth testing, standardised validated questionnaires (including AUDIT and LDH), physical examination, and advanced imaging using MRI-PDFF and MRE.

Among 374 adults with SLD, the prevalence of MASLD, MetALD, and ALD was 90.1%, 6.4%, and 3.5%, respectively. PEth had a robust diagnostic accuracy in the detection of MetALD (AUROC 0.81, 95%CI 0.73-0.89) and the Youden cut-off was 25 ng/mL. In head-to-head comparative efficacy analysis, PEth was both statistically and clinically superior to all previously used indirect alcohol biomarkers for diagnosing MetALD, including aspartate aminotransferase/alanine aminotransferase ratio, mean corpuscular volume, gamma glutamyltransferase, and ALD/NAFLD index (p < 0.05).

PEth outperforms previously used non-invasive tests in differentiating MetALD from MASLD and has the potential to change clinical practice by enhancing the subclassification of SLD.

Limited and inconclusive evidence exists regarding the correlation between serum zinc levels and non-alcoholic fatty liver disease (NAFLD) and advanced fibrosis. The objective of this cross-sectional study was to investigate the association between serum zinc concentration and both NAFLD and advanced liver fibrosis among the United States (US) adults. 3398 subjects from National Health and Nutrition Examination Survey (NHANES) 2011-2016 were included. Serum zinc concentration was measured by inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS). NAFLD was diagnosed with Hepatic Steatosis Index (HSI), and advanced fibrosis risk was assessed by NAFLD Fibrosis Score (NFS). Weighted logistic regression and restricted cubic splines (RCS) were used to examine the association between serum zinc concentration and NAFLD and advanced fibrosis. Linear trend tests were conducted by incorporating the median of serum zinc quartiles as a continuous variable in the models. We employed sensitivity analysis and subgroup analysis to enhance the robustness of our results. The results from the RCS regression revealed no evident nonlinear relationship between serum zinc concentration and the presence of NAFLD and advanced fibrosis (p-nonlinear > 0.05). Compared with those in the lowest quartile (Q1) of serum zinc concentrations, the odds ratios (95% confidence intervals) of NAFLD were 1.49 (0.89,2.49) in Q2, 0.99 (0.68,1.45) in Q3, and 2.00 (1.40,2.86) in Q4 (p-trend = 0.002). Similarly, the odds ratios (95% confidence intervals) for advanced fibrosis in Q2-4 compared to Q1 were 0.86 (0.50,1.47), 0.60 (0.26,1.39), and 0.41 (0.21,0.77), respectively (p-trend = 0.006). Subgroup analyses and sensitivity analyses reinforce the same conclusion. The investigation revealed a positive linear relationship between serum zinc concentrations and the probability of developing NAFLD. Conversely, an inverse correlation was observed between serum zinc concentrations and the incidence of advanced liver fibrosis among individuals diagnosed with NAFLD.

Liver transplantation (LT) is the standard of care for both end-stage liver failure and hepatocellular carcinoma (HCC). Side effects of the main used immunosuppressive drugs have a noteworthy impact on the long-term outcome of LT recipients. Consequently, to achieve a balance between optimal immunosuppression and minimal side effects is a cornerstone of the post-LT period. Today, there are no validated markers for overimmunosuppression and underimmunosuppression, only a few drugs have therapeutic drug monitoring, and immunosuppression regimens vary from center to center and from country to country. Currently, there are many drugs with different efficacy and safety profiles. Using different agents permits a decrease in the dosage and minimizes the toxicities. A small subset of recipients achieves immunotolerance with the chance to stop immunosuppressive therapy. This article focuses on the side effects of immunosuppressive drugs, which significantly impact long-term outcomes for LT recipients. The primary aim is to highlight the balance between achieving effective immunosuppression and minimizing adverse effects, emphasizing the role of personalized therapeutic strategies. Moreover, this review evaluates the mechanisms of action and specific complications associated with immunosuppressive agents. Finally, special attention is given to strategies for reducing immunosuppressive burdens, improving patient quality of life, and identifying immunotolerant individuals.

The aim of this study is to analyze association between liver fibrosis with CVE, incident diabetes, and cirrhosis complications.

Historic cohort of biopsy-proven MASLD patients, divided into two groups: F0-F2 vs F3-F4 fibrosis. Baseline data included metabolic traits and liver function tests. Patients were contacted and scheduled for laboratory analysis and elastography. Endpoints were (a) CVE, defined as any of acute myocardial infarction, coronary stenting, ischemic cardiopathy, and stroke; (b) incident diabetes; (c) cirrhosis complications. Baseline data were collected at the time of liver biopsy, while follow-up data were recovered through personal interview or medical records. A stepwise logistic regression determined predictive variables for each endpoint.

Study population included 220 patients with median age 53 years, and 145 were women; baseline fibrosis was F0-F2 in 165 patients and F3-F4 in 55 patients; median follow-up was 9.9 years. A higher percentage of F3-F4 patients had CVE (29.4%) than F0-F2 ones (13.1%) (hazard ratio 2.42; 95% CI: 1.26-4.6; P = 0.008). Incident diabetes occurred in 53.3% of F3-F4 and 20.2% of F0-F2 cohort (hazard ratio 3.04; 95% CI: 1.99-4.86; P < 0.001); cirrhosis complications occurred in 9/55 F3-F4 patients and in 1/165 F0-F2 ones (hazard ratio 26.3; 95% CI: 3.3-208.3; P = 0.002). Multivariate analysis confirmed liver fibrosis as an independent predictor of incident diabetes and cirrhosis complications. CVE were associated with baseline diabetes and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio.

In a cohort of 220 MASLD patients followed for 9.9 years, baseline F3-F4 was associated with incident diabetes and cirrhosis complications. AST/ALT ratio and diabetes were associated with CVE.

The study aimed to assess the effect of COVID-19 on hepatic lipid (HL) content, fibrosis risk, and adiposity in persons with type 2 diabetes.

Participants with type 2 diabetes with a history of mild COVID-19 (n=15, age 58±12 years, body mass index 30.9±5.2 kg/m2) were examined before (baseline) and 1 year (12±2 months) after (follow-up) recovery from COVID-19. Investigations for changes in metabolic risk comprised clinical examination, fasting blood sampling and MR-based measurements. Potential changes were corrected with the time course of the respective parameters in a group of participants who did not contract COVID-19 over the same time course (n=14, 61±6 years, 30.0±4.6 kg/m2).

COVID-19 resulted in a relative increase in HL content of 56% (95% CI 18%, 106%; p=0.04) measured as proton density fat fraction (HL-PDFF), corrected for the time course in the absence of COVID-19. While no changes in hepatic stiffness and volume, intramyocellular lipids, whole-body, subcutaneous and visceral adipose tissue volumes as well as homeostatic model assessment of insulin resistance and beta-cell function were observed.

History of COVID-19 in persons with type 2 diabetes is associated with higher HL-PDFF after 1 year following recovery from infection.

NCT01055093.

De novo lipogenesis (DNL) is a metabolic pathway that converts carbohydrates into fatty acids, primarily occurring in the liver and, to a lesser extent, in adipose tissue. While hepatic DNL is highly responsive to dietary carbohydrate intake and regulated by insulin via transcription factors like SREBP-1c, adipose DNL is more modest and less sensitive to dietary overfeeding. Dysregulated DNL contributes to metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Lifestyle interventions, such as physical exercise, ketogenic diets, and time-restricted eating (TRE) offer promising strategies to regulate DNL and improve metabolic health. Physical exercise enhances glucose uptake in muscles, reduces insulin levels, and promotes lipid oxidation, thereby suppressing hepatic DNL. Endurance and resistance training also improve mitochondrial function, further mitigating hepatic triglyceride accumulation. Ketogenic diets shift energy metabolism toward fatty acid oxidation and ketogenesis, lower insulin, and directly downregulate lipogenic enzyme activity in the liver. TRE aligns feeding with circadian rhythms by optimizing AMP-activated protein kinase (AMPK) activation during fasting periods, which suppresses DNL and enhances lipid metabolism. The combined effects of these interventions demonstrate significant potential for improving lipid profiles, reducing hepatic triglycerides, and preventing lipotoxicity. By addressing the distinct roles of the liver and adipose DNL, these strategies target systemic and localized lipid metabolism dysregulation. Although further research is needed to fully understand their long-term impact, these findings highlight the transformative potential of integrating these approaches into clinical practice to manage metabolic disorders and their associated complications.

Improving the management of metabolic dysfunction-associated steatotic liver disease (MASLD) in Primary Care requires a good knowledge of the disease. This study evaluated the knowledge of biomarkers and comorbidities associated with the disease among Primary Care Physicians (PCPs), the resources available for diagnosis, and the relationship with hepatologists.

Cross-sectional study based on an anonymous email survey sent to PCPs actively practicing at the time of distribution. Retired professionals were excluded. The survey comprised 29 questions grouped into 3sections: 1. Sociodemographic characteristics, 2. Relationship with the gastroenterology department, 3. Diagnosis and management of MAFLD.

A total of 362 responses were received (10.23% participation). Of the respondents, 64.2% were women, and the most participative age group was 50-59 (29.4%). Cantabria, Catalonia, Andalusia, Castilla-León and Madrid were the regions with the highest response rates. 81.5% of PCPs did not have protocols for diagnosis and management, and while two-thirds were familiar with the Fib-4 marker, only half used it. Having protocols increased the use of Fib-4 (OR 4.41; 95%CI 1.68-11.53). A total of 81.5% recognized the importance of extrahepatic comorbidities, and 92% actively screened for cardiovascular risk factors. Elastography was considered useful by 58.7%, but only 11% had access to it. 72% of PCPs had no relationship with specialists, although 60% had access to a Hepatology Unit.

It is necessary to improve knowledge of MAFLD, strengthen collaboration between care levels, and establish standardized management protocols.

It is critical to assess the extent and progression of liver fibrosis for patients to receive suitable treatments, but its diagnostic methods remain unmet. Extracellular matrix protein 1 (ECM1) has previously been reported to be a key factor in the induction and progression of liver fibrosis. However, little is known about the use of ECM1 as a biomarker to evaluate fibrosis. In a CCl4-induced mouse model of liver fibrosis, the present study demonstrated that ECM1 decreased with gradually increasing fibrosis. Using biopsy as a reference, the serum ECM1 levels decreased with increasing fibrosis stage in 247 patients with liver fibrosis, but there were no significant changes between fibrosis stage 2 and stage 0-1. To improve the performance of ECM1, age, platelet count, and ECM1 concentration were combined to calculate an EPA (ECM1-platelet-age) score (ranging from 0 to 10). The areas under the receiver operating characteristic curve of the EPA scores for the detection of F⩾2, F⩾3, and F4 were 0.6801, 0.7377, and 0.8083, respectively, which showed a comparable or significantly greater diagnostic performance for assessing fibrosis than that of the AST/ALT ratio, APRI score, or FIB-4 score. In HBV patients following antiviral treatment, the dynamics of the EPA score depended on the status of liver fibrosis development. The accuracy of the EPA score in predicting fibrosis regression and progression was 66.00% and 71.43%, respectively, while that of the LSM, another useful method for monitoring hepatic fibrosis changes during treatment, was only 52.00% and 7.14%, respectively. Compared with healthy controls, there were lower levels of serum ECM1 in HBV patients and individuals with HCV infection, MAFLD, ALD, PBC, and DILI. These findings suggested that individuals with reduced ECM1 levels may have a risk of developing liver injury, and further examinations or medical care are needed. In conclusion, the ECM1-containing EPA score is a valuable noninvasive test for staging fibrosis and predicting the progression of liver fibrosis. Additionally, ECM1 alone is an indicator for distinguishing patients with liver injury from healthy controls.

Severity of fibrosis is the driver of liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD), and non-invasive testing such as fibrosis-4 (FIB-4) score is utilized for risk stratification. We aimed to determine if primary care patients at risk for MASLD and advanced fibrosis were evaluated with subsequent testing. A secondary aim was to determine if at-risk patients with normal aminotransferases had advanced fibrosis.

Primary care patients at increased risk for MASLD with advanced fibrosis (n = 91,914) were identified using previously established criteria. Patients with known alternative/concomitant etiology of liver disease or cirrhosis were excluded. The study cohort included patients with calculated FIB-4 score in 2020 (n = 52,006), and stratified into low, indeterminate, and high likelihood of advanced fibrosis. Among those at indeterminate/high risk, rates of subsequent testing were measured.

Risk stratification with FIB-4 characterized 77% (n = 40,026) as low risk, 17% (n = 8847) as indeterminate, and 6% (n = 3133) as high risk. Among indeterminate/high-risk patients (n = 11,980), 78.7% (n = 9433) had aminotransferases within normal limits, 0.95% (n = 114) had elastography, and 8.2% (n = 984) were referred for subspecialty evaluation.

In this cohort of primary care patients at risk for MASLD with fibrosis, the FIB-4 score identified a substantial proportion of indeterminate/high-risk patients, the majority of which had normal aminotransferase levels. Low rates of subsequent testing were observed. These data suggest that a majority of patients at increased risk for liver-related outcomes remain unrecognized and highlight opportunities to facilitate their identification.

The association between Life's Essential 8 (LE8) score and all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) remains unknown.

This population-based prospective cohort study analyzed data of participants aged 20-79 years in the National Health and Nutrition Examination Survey from 2005 to 2018, with linked mortality information until 2019. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for the association between different cardiovascular health (CVH) scores and all-cause mortality in participants with MASLD.

Among 11,988 participants, 4109 (34.3 %) were diagnosed with MASLD. During the median 7.8 years of follow-up, 912 deaths were recorded. Unexpectedly, the total LE8 CVH score was not associated with all-cause mortality in patients with MASLD (all P > .05). However, individuals with MASLD with moderate and poor LE8 health behaviors scores exhibited an increased risk of all-cause mortality (moderate: HR, 1.51; 95 % CI, 1.05-2.17; poor: HR, 2.32; 95 % CI, 1.64-3.30), particularly among patients with advanced fibrosis (moderate: HR, 1.77; 95 % CI, 1.07-2.92; poor: HR, 2.43; 95 % CI, 1.23-4.78). Population-attributable fraction estimates suggest that 35.0 % of all-cause mortality attributed to poor or moderate health behaviors scores could be avoided if ideal CVH metrics were achieved in all patients with MASLD.

These findings demonstrate a significant association between the LE8 health behaviors score and all-cause mortality in patients with MASLD, highlighting the usefulness of this score in optimizing risk management strategies for MASLD in future clinical practice.

Gaucher disease (GD) is a rare genetic disorder with multi-system involvement. Liver fibrosis is a long-term complication of GD, potentially leading to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There are currently no validated clinical tools for the monitoring of liver fibrosis in patients with GD. In this study, we aim at assessing the validity of common fibrosis-predicting scores, developed for other diseases, for the use in GD, using transient elastography as a gold-standard, as well as developing the first GD-specific liver fibrosis predicting score. We enrolled 19 adult patients with GD who had been on treatment for a minimum of 1 year on enzyme replacement therapy or substrate reduction therapy and who had no evidence of any other liver disease except GD or metabolic-associated steatotic liver disease (MASLD), which is a common comorbidity of GD. We analyzed the correlation between liver stiffness and genotype, treatment modality (imiglucerase or other therapies), clinical severity, and clinical laboratory tests. We found that the common liver fibrosis scores APRI, FIB-4, and NFS did not accurately predict liver fibrosis in people with GD. We also found that male sex, the DS3 score, AST, and GGT levels significantly correlated with liver stiffness, and used these to create a simple but accurate fibrosis-predicting score specifically for GD (the "Gaucher liver fibrosis score", or GLFS), with high accuracy (AUC = 0.8571, p = 0.0206). We believe that our new GLFS may be used in clinical practice to help prioritize GD patients for closer monitoring of liver fibrosis.

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease worldwide, consisting of a broad spectrum of diseases such as simple steatosis (NAFL), non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatic inflammation plays a key role in the pathophysiology of NAFLD. Inflammatory mediators such as cytokines and chemokines are considered as contributing factors to NAFLD development and progression. In the present study, we aimed to investigate the inflammatory protein signatures as predictive disease-specific markers for non-alcoholic fatty liver disease (NAFLD). This cross-sectional study included healthy control (n = 64), NAFL (n = 109), and NASH (n = 60) human subjects. Serum concentrations of various cytokines and chemokines were evaluated using sensitive multiplex assays. We used principal component analysis (PCoA) to reveal distinct differences in the levels of cytokines and chemokines between each of the study groups. Further, a random forest classification model was developed to identify the panel of markers that could predict diseases. The protein-protein network analysis was performed to determine the various signaling pathways associated with the disease-specific panel of markers. Serum concentrations of TNF-α, IL-1β, IL-1ra, G-CSF, PDGF-BB, MCP-1, MIP-1a, MIP-1b, RANTES, eotaxin, IL-8 and IP-10 were significantly increased in NASH group as compared to control group. Furthermore, serum concentrations of IL-9 and IL-13 were significantly lower in the NASH group, whereas IL-2 levels were significantly decreased in the NAFL group when compared to the control group. PCoA results demonstrated statistically significant differences in cytokines and chemokines between each of the study groups (PERMANOVA p = 0.001; R2 = 0.102). RANTES, IL-1ra, MIP-1b, IL-2, and G-CSF could differentiate the NAFL group from the controls; G-CSF, IL-1ra, TNF-α, RANTES, and IL-9 could differentiate the NASH group from the controls; and G-CSF, IL-9, IL-13, eotaxin, and TNF- α could differentiate the NASH group from the NAFL group. Our protein-protein network revealed that these markers are involved in cytokine-cytokine receptor interaction, Th1 and Th2 cell differentiation, TNF, chemokine, JAK/STAT, P13K/Akt, TLR, NOD-like receptor, NF-kB, and adipocytokine signaling pathways which might be responsible for disease pathogenesis. Our study findings revealed a set of distinct cytokine and chemokine markers and they might be considered as biomarkers in distinguishing NASH from NAFL. Future multicentre studies with larger sample size are recommended to determine the potential utility of these panels of markers.

The long-term survival rate of patients with pancreatic ductal adenocarcinoma has improved alongside the development of multidisciplinary treatment, and there is now demand for less invasive surgery that maintains postoperative pancreatic function. We evaluated the efficacy of pancreas-preserving distal pancreatectomy in terms of oncologic parameters and postoperative pancreatic function.

The data of 98 consecutive patients who underwent distal pancreatectomy for the treatment of pancreatic ductal adenocarcinoma between 2012 and 2022 in our institution were retrospectively analyzed. The surgical outcomes, overall survival, and postoperative pancreatic function were compared between pancreas-preserving distal pancreatectomy, in which the pancreatic stump was distal to the left margin of the portal vein on postoperative computed tomography, and conventional distal pancreatectomy.

Sixteen patients (16%) underwent pancreas-preserving distal pancreatectomy. Fewer lymph nodes were dissected in the pancreas-preserving distal pancreatectomy group than the conventional distal pancreatectomy group (19 vs 31, respectively; P < .01); however, the R0 resection rate (94% vs 93%, respectively; P = 1.00), recurrence-free survival, and overall survival were similar. Similar results were obtained in an analysis limited to patients with pancreatic ductal adenocarcinoma in the pancreatic tail. Patients who underwent pancreas-preserving distal pancreatectomy were less likely to develop worsening of their diabetes than those who underwent conventional distal pancreatectomy (19% vs 39%, respectively; P = .16). Nonalcoholic fatty liver disease newly developed in 22% of the patients who underwent conventional distal pancreatectomy but in none of those who underwent pancreas-preserving distal pancreatectomy (P = .04).

The pancreatic transection site should be distally located to preserve postoperative pancreatic function when R0 resection can be achieved.

Obesity is associated with varying degrees of metabolic dysfunction. In this study, we aimed to discover markers of the severity of metabolic impairment in men with obesity via a multiomics approach.

Thirty-two morbidly men with obesity who were candidates for Roux-en-Y gastric bypass (RYGB) surgery were prospectively followed. Nine healthy adults served as controls. Deep phenotyping, including targeted metabolomics, transcriptomics, and brain magnetic resonance imaging (MRI), was performed.

Testosterone emerged as a key contributor to phenotypic variability via principal component analysis and was therefore used to further categorize obese patients as having or not having hypogonadotropic hypogonadism (HH). Despite having comparable body mass indices, obese individuals with HH presented with worse metabolic defects than obese individuals without HH, including higher insulin resistance, as well as MRI signs of hypothalamic inflammation and a specific blood transcriptomics signature. The upregulated genes were involved mainly in inflammation, mitochondrial function, and protein translation. Integration of gene expression and clinical data revealed high FGF21 and low cortisol levels as the top markers correlated with the transcriptomic signature of metabolic risk. Following RYGB-induced substantial weight loss, testosterone levels markedly increased in both obese individuals with and without HH, challenging the current definition of hypogonadism. A longitudinal study in a subset of men with obesity following bariatric surgery revealed a unique FGF21 trajectory with a sharp peak at one month post-RYGB that correlated with metabolic and reproductive improvements.

Combining clinical, biochemical, and molecular markers allows adequate stratification of metabolic risk in men with obesity and provides novel tools for personalized care.

Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver disease worldwide, affecting one-fourth of the world's population. With more than half of the world's population, the Asia-Pacific region contributed 62.6 % of liver-related fatal incidents in 2015. Currently, liver imaging techniques such as computed tomography (CT), nuclear magnetic resonance (NMR) spectroscopy, and ultrasound are non-invasive imaging methods to diagnose the disease. A liver biopsy is the gold standard test for establishing the definite diagnosis of non-alcoholic steatohepatitis (NASH). However, there are still significant problems with sample variability and the procedure's invasiveness. Numerous studies have indicated various non-invasive biomarkers for both fibrosis and steatosis to counter the invasiveness of diagnostic procedures. Metabolomics could be a promising method for detecting early liver diseases, investigating pathophysiology, and developing drugs. Metabolomics, when utilized with other omics technologies, can result in a deeper understanding of biological systems. Metabolomics has emerged as a prominent research topic, offering extensive opportunities to investigate biomarkers for liver diseases that are both sensitive and specific. In this review, we have described the recent studies involving the use of a metabolomics approach in the diagnosis of liver diseases, which would be beneficial for the early detection and treatment of liver diseases.

Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.

This was a four-group, prospective, randomized, parallel, open label study in which 100 biopsy-proven NASH patients were selected, stratified to diabetics and non-diabetics and randomized with 1:1 allocation to either 30 mg pioglitazone or 10 mg dapagliflozin, once daily for 24 weeks. Histological evaluation, anthropometric measures, hepatic, metabolic biochemical markers, fibrosis non-invasive markers, quality of life (QOL) and medications adverse events were examined.

Dapagliflozin showed a comparable histological effect to pioglitazone in both diabetic and non-diabetic patients (P>0.05). As assessed by transient elastography, it also showed a comparable effect on liver fibrosis grade improvement from baseline in diabetics (P=0.287) versus a significant superiority in non-diabetics (P=0.018). Dapagliflozin showed a significant superiority in all anthropometric measures (P<0.001) and QOL (P<0.05) among both diabetics and non-diabetics. There was a significant interaction between interventions and diabetes status on change from baseline of hepatic and metabolic panel collectively (P=0.023) in favor to dapagliflozin among diabetics.

Compared to pioglitazone, dapagliflozin had a comparable effect histologically, superior effect biochemically among diabetics and superior effect on liver fibrosis, steatosis and insulin resistance among non-diabetics.

The study was registered on clinicaltrials.gov, identifier number NCT05254626.

The treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) has focused on the control of comorbidities. Silybum marianum (SM) and alpha-lipoic acid (ALA) have shown antioxidant and adjuvant effects on the control of metabolic disorders.

To evaluate whether the SM-ALA formulation (LUDLEV®), in combination with the Mediterranean diet (MD), could improve MASLD-related liver injury.

A randomized, double-blind clinical trial was conducted on patients with MASLD. Administration of SM-ALA plus MD (group A) vs placebo plus MD (group B) was compared for 24 weeks. At baseline and weeks 12 and 24, anthropometric measurements, metabolic parameters, and liver function were analyzed. Clinical effectiveness was evaluated through transient elastography.

Fifty patients aged 54 ± 10 years were included, and the majority (74%) were female. Reduced visceral fat and umbilical circumference were reported in both groups, with significance in group A (P = 0.045 and 0.003, respectively). The decrease in controlled attenuation parameter was gradual and maintained at 12 and 24 weeks in group A (P = 0.026), whereas in group B the decrease was greater at week 12 and remained unchanged at week 24 (∆controlled attenuation parameter: -27 dB/m). Mild adverse effects were reported in 4 patients in group A (16%) and 4 patients in group B (16%), with no significant differences between groups (P = 0.641).

SM-ALA (LUDLEV®) combined with the MD can promote the improvement of metabolic parameters, reducing visceral fat and hepatic steatosis in Mexican patients with MASLD.

The present study explored the association between biological aging (BA), healthy eating index-2015 (HEI-2015) and non-alcoholic fatty liver disease (NAFLD) in the general population of the United States.

We used data from the NHANES database between 2017-2018 years to conduct the study. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS), and subgroup analysis were performed to analyze the association of BA and HEI-2015 with prevalence of NAFLD and the mediation effect of HEI-2015 was also discussed. Additionally, generalized additive model was conducted to investigate the association of BA and HEI-2015 with ZJU index, BARD score, and NAFLD fibrosis score.

There was a total of 2,421 individuals. RCS shown that BA was positively correlated with prevalence of NAFLD, while HEI-2015 was negative correlated with NAFLD risk. After adjusting for interfering factors, compared with the lowest quartiles of BA and HEI-2015, the odds ratios with 95% confidence intervals for NAFLD across the quartiles were (1.24 (0.84, 1.84), 2.07 (1.15, 3.73) and 2.49 (1.16, 5.38)) and (0.89 (0.66, 1.18), 0.87 (0.65, 1.16) and 0.64 (0.46, 0.87)), respectively. The BA was linear positive with ZJU index, BARD score and NAFLD fibrosis score. However, the linear negative correlation existed between HEI-2015 and ZJU index, BARD score and NAFLD fibrosis score. Mediation analysis showed that the positive correlation between BA and NAFLD could be mediated and weakened by HEI-2015.

The prevalence of NAFLD gradually increases with BA, but this positive association can be weakened by the healthy diet.

The objective of this research was to explore the possible link between markers of liver fibrosis and survival rates in a group of adults who have been diagnosed with both chronic kidney disease (CKD) and coronary artery disease (CAD).

The National Health and Nutrition Examination Survey (NHANES) data (1999-2018) for participants with both CAD and CKD were analyzed. The fibrosis-4 index (FIB-4), Nonalcoholic Fatty Liver Score (NFS), Forns index, and aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio were identified as crucial biomarkers. All-cause and cardiovascular disease (CVD) mortality were primary outcomes, assessed using Cox models, Kaplan-Meier curves, and receiver operating characteristic (ROC) analysis.

A total of 1,192 CKD and CAD patients were included. The Cox regression analysis revealed substantial correlations between elevated FIB-4, NFS, Forns index, and AST/ALT levels and a heightened risk of all-cause (hazard ratio [HR]: 1.188, 95% confidence interval [CI]: 1.108-1.274; HR: 1.145, 95% CI: 1.069-1.227; HR: 1.142, 95% CI: 1.081-1.201; HR: 1.316, 95% CI: 1.056-1.639, respectively) and CVD mortality (HR: 1.133, 95% CI: 1.007-1.275; HR: 1.155, 95% CI: 1.024-1.303; HR: 1.208, 95% CI: 1.109-1.316 and HR: 1.636, 95% CI: 1.203-2.224, respectively). The ROC analysis indicated comparable predictive accuracy for all three biomarkers, with AST/ALT showing slightly superior performance.

Liver fibrosis markers, including AST/ALT, NFS, Forns index and FIB-4, are significant mortality predictors in CAD-CKD patients. The AST/ALT ratio, being easily measurable, may serve as an effective predictive tool for risk stratification in this population.

Alpha-Glutathione-S-transferase (alphaGST) is a liver enzyme whose serum levels increase with the worsening of fibrosis in alcoholic and viral chronic hepatitis. Its usefulness in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) remains unexplored. From January 2016 to December 2017, 200 patients with MASLD and 30 controls were enrolled. AlphaGST serum levels were measured. Variables related to advanced fibrosis (AF) were selected via Principal Component Analysis (PCA), and the best cut-off (BCO) was estimated using ROC analysis. Liver stiffness measurement (LSM), NAFLD fibrosis (NFS), Fibrosis-4 (FIB-4), and BMI-AST/ALT Ratio-Diabetes (BARD) scores were determined. The first acute cardiovascular events (ACE) in ACE-naïve subjects were recorded over five years. A validation cohort of 60 MASLD patients was enrolled from January 2018 to May 2019 and followed for five years. AlphaGST levels increased with fibrosis stage (p < 0.0001) in both cohorts, showing high accuracy in predicting AF (TrC: AUC 0.89, VlC: AUC 0.89). PCA-selected variables were HbA1c, HDL, and alphaGST, forming the "FLAME" model. FLAME showed superior predictive performance for AF and ACEs compared to other models and scores. FLAME represents a novel tool that accurately predicts AF and ACEs in MASLD.

Global metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is estimated at 30% and projected to reach 55.7% by 2040. In the Veterans Affairs (VA) healthcare system, an estimated 1.8 million veterans have metabolic dysfunction-associated steatohepatitis (MASH).

Adult patients at risk for MASLD in a VA healthcare system underwent Fibrosis-4 (FIB-4) and Enhanced Liver Fibrosis (ELF®) testing. Referral rates and cost savings were compared among 6 noninvasive testing (NIT) strategies using these 2 tests independently or sequentially at various cutoffs.

Enrolled patients (N = 254) had a mean age of 65.3 ± 9.3 years and mean body mass index (BMI) of 31.7 ± 6, 87.4% male: 78.3% were non-Hispanic/Latino, and 96.5% had type 2 diabetes mellitus (T2DM). Among the 6 evaluated strategies, using FIB-4 followed by ELF at a 9.8 cutoff yielded the highest proportion of patients retained in primary care without need of referral to hepatology clinic (165/227; 72.7%), and was associated with the lowest costs ($407.62). Compared to the FIB-4 only strategy, FIB-4/ELF with a 9.8 cutoff strategy resulted in 26% fewer referrals and 8.47% lower costs. In the subgroup of patients with BMI >32, there were 25.17% fewer referrals and costs were 8.31% lower.

Our study suggests that sequential use of ELF with a 9.8 cutoff following indeterminate FIB-4 tests results in lower referral rates and lower care costs in a veteran population at risk of MASLD. Adding ELF as a sequential test after indeterminate FIB-4 might help reduce the number of referrals and overall cost of care.

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).