Metabolic dysfunction-associated steatotic liver disease (MASLD) is a type of fat accumulation in the liver that can lead to cirrhosis and chronic liver disease. MASLD is recognized as the most frequent of liver-associated deaths worldwide. The SERPINA1 gene encodes a serine protease protein that plays a pivotal role in the pathogenesis of liver deficiencies. In this study, we aimed to evaluate the genetic association between rs6647 (M1), rs709932 (M2), and rs1303 (M3) variants in the SERPINA1 gene and the risk of MASLD in an Iranian population.

In this case-control study, 120 patients affected by MASLD and 120 healthy subjects participated. The Nephelometry system measured serum levels of α1-antitrypsin (A1AT). Biochemical tests were conducted to assess serum levels of blood parameters using commercially available kits. DNA extraction was performed using the salting-out method, followed by the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method for genotyping. Statistical analysis was performed by SPSS v16.0.

The findings showed that the rs6647 G allele significantly increased the risk of MASLD. The G allele in codominant, dominant, and over-dominant models caused an increase in the risk of MASLD. Additionally, the rs709932 T allele was more frequent among patients compared to healthy subjects and significantly enhanced the risk of MASLD. The T allele in the codominant and recessive models indicated a high risk for MASLD in our population. The G allele of rs1303 caused an enhancement in the mean serum levels of A1AT in the MASLD group.

Our results show an association between SERPINA1 gene variants and the risk of MASLD. The rs6647 (M1) and rs709932 (M2) variants of the SERPINA1 gene increased the risk of disorder in our population.

The transition in terminology from fatty liver disease to metabolic dysfunction-associated steatotic liver disease (MASLD) marks a considerable evolution in diagnostic standards. This new definition focuses on liver fat accumulation in the context of overweight/obesity, type 2 diabetes, or metabolic dysfunction, without requiring the exclusion of other concurrent liver diseases. The new definition also provides clear guidelines for defining alcohol consumption in relation to the disease. MASLD is currently acknowledged as the most widespread liver disorder globally, affecting ~25% of the population. Despite the extensive array of clinical trials conducted in recent years, the number of approved treatments for metabolic dysfunction-associated fatty liver disease is very limited. In the review critically evaluates the results of clinical trials of related drugs and assesses the future directions for drug development trials. The renaming of MASLD presents new challenges and opportunities for the design of clinical trials and the selection of target populations for drug development.

The association between remnant cholesterol (RC) with obesity phenotypes remains unclear.

This study designed to evaluate the association between RC and obesity phenotypes using data from the National Health and Nutrition Examination Survey (NHANES). The classification systems for obesity phenotypes encompassed both preclinical/clinical obesity and obesity stages, which were assessed based on two authoritative obesity guidelines: the 2025 clinical obesity guideline, and the 2016 obesity guideline established by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). Participants were selected according to the diagnostic criteria for obesity proposed in the 2025 clinical obesity guideline and were categorized into tertiles based on their RC levels. Their obesity phenotypes, obesity-related clinical manifestations, obesity-related comorbidities, and characteristics were then described. Logistic regression analyses and restricted cubic spline (RCS) models were used to analyze the relationship between RC and adverse obesity phenotypes. Sensitivity analyses were conducted in patients not receiving lipid-lowering drugs.

This study comprised 3,207 adult participants, revealing distinct prevalence patterns: 47.80% exhibited preclinical obesity and 17.81% showed clinical obesity, while obesity stage stratification demonstrated 0%, 12.76%, and 21.63% prevalence for stage 0, 1, and 2, respectively. Multivariable regression analyses demonstrated dose-response relationship between RC levels and adverse obesity phenotypes, with individuals in the highest RC tertile showing significantly elevated risks of clinical obesity (OR 1.95, 95% CI 1.19-3.19) and obesity stage progression (OR 1.96, 95% CI 1.06-3.62) compared to the lowest tertile reference group. RCS analyses further revealed similar "J"-shaped association between RC levels and adverse obesity phenotypes (P for nonlinearity < 0.001), sharing a common inflection point at 0.51 mmol/L. The sensitivity analyses confirmed the consistency of the results among patients who were not receiving lipid-lowering therapy.

RC was found to be positively and independently associated with adverse obesity phenotypes, particularly when RC levels exceeded 0.51 mmol/L, demonstrating a similar "J"-shaped association. It is recommended that clinicians monitor RC levels for obese patients as a primary screening indicator for adverse phenotypes of obesity.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a chronic liver disease affecting 25% of the European population, with rising global incidence. Liver damage includes ballooning, steatosis, inflammation and fibrosis. Associated brain disorders include sleep, cognitive issues, anxiety, and depression. While neurological complications in advanced MASLD are well documented, early cerebral manifestations remain largely unexplored. This study aimed at developing an MASLD rat model to assess the onset of early brain damage, focusing on impairments of the circadian cycle rhythm and associated neuroinflammation. Sprague Dawley rats were divided into two groups: one received a high-fat, high-cholesterol (HFHC) diet for 90 days, while the other received a standard diet. Histological analysis showed significant hepatic steatosis, ballooning, and inflammation in the HFHC group (p < 0.01). These lesions correlated with elevated hepatic triglycerides (p < 0.01), increased Alanine Aminotransferase, Aspartate Aminotransferase, total cholesterol, and low-density lipoprotein, alongside decreased plasma high-density lipoprotein. Behavioural analysis using activity wheels revealed that the HFHC rats steadily maintained their activity level during the rest periods when compared with controls (p < 0.05). This behavioural alteration occurred alongside neuroinflammation, demonstrated by changes in the expression of 36 and 17 inflammatory mediators in the cerebellum and frontal cortex respectively. These changes were associated with an increase in the expression of glial cell markers (Aif1 and Gfap genes) and an increase in the number of microglial cells, affecting the frontal cortex and cerebellum differently. This rat model of early MASLD shows circadian rhythm disturbances, which could reflect sleep disorders in humans. These early brain disturbances specific to MASLD, which occur before the symptoms of liver disease become clinically apparent, could therefore be used as an early diagnosis marker for MASLD patients.

Polycystic ovary syndrome (PCOS) is linked to non-alcoholic fatty liver disease (NAFLD). Biochemical, sex hormonal, and anthropometric indicators have been explored for screening NAFLD in PCOS patients. However, the accuracy of NAFLD screening using these indicators in PCOS patients remains uncertain. This study aimed to identify biochemical, sex hormonal, and anthropometric indicators associated with NAFLD in overweight and obese PCOS patients and assess the diagnostic efficacy of combined indicators.

This cross-sectional study (Clinical trial number ChiCTR1900020986; Registration date January 24th, 2019) involved 87 overweight or obese women with PCOS (mean age 29 ± 4 years). Measurements included anthropometric indices, biochemistry, sex hormone levels, and liver proton density fat fraction (PDFF). Correlation analysis, intergroup comparisons, and logistic regression analysis were used to identify risk factors for NAFLD (PDFF > 5.1%). The receiver operating characteristic curve, area under the curve (AUC), sensitivity, specificity, positive predictive value, and negative predictive value were used to determine cut-off values and evaluate diagnostic accuracy.

Liver PDFF was 7.69% (3.93%, 14.80%) in overweight and obese PCOS patients, with 67.8% diagnosed with NAFLD. NAFLD was associated with increased body mass index (BMI), abdominal circumference (AC), and triglyceride, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), glucose, insulin, and free testosterone (FT) levels, and with decreased high-density lipoprotein-cholesterol (HDL-C) and sex hormone-binding globulin (SHBG) levels (P < 0.05). Risk factors for NAFLD in PCOS included BMI > 26.8 kg/m2, AC > 88.3 cm, triglyceride > 1.57 mmol/L, TC > 4.67 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, FT > 7.6 pg/mL and SHBG < 25 nmol/L (β = 1.411-2.667, P < 0.005). A multi-indicator model including triglycerides, LDL-C, glucose, insulin, and SHBG showed higher diagnostic accuracy (AUC = 0.899, P < 0.001) for screening NAFLD in PCOS patients than single indicators (AUC = 0.667-0.761, P < 0.05).

Overweight and obese PCOS patients have higher incidences of liver PDFF and NAFLD. A multi-indicator model including triglycerides > 1.57 mmol/L, LDL-C > 3.31 mmol/L, glucose > 4.83 mmol/L, insulin > 111.35 pmol/L, and SHBG < 25 nmol/L is highly accurate for screening NAFLD in overweight and obese PCOS patients.

Background: An association between education levels and liver disease has been confirmed, but not yet with metabolic dysfunction-associated steatotic liver disease (MASLD). The aim is to investigate the relationship between education and MASLD in two cohorts in southern Italy. Methods: The study cohort included 2909 participants assessed during the third recall of the MICOL study and the second of NUTRIHEP, subdivided into four groups based on education levels. Results: A strong protective association was found between MASLD and higher education levels. Participants had an OR = 0.50 (p < 0.001, 0.36 to 0.69 95% C.I.), OR = 0.29 (p < 0.001, 0.21 to 0.41), and OR = 0.24 (p < 0.001, 0.16 to 0.37 95% C.I.) for middle, high school, and graduate education, respectively. Conclusions: This study's findings indicate that there is an association linking MASLD with education level, i.e., having a lower education level increases the risk of liver disease, and a proper policy to regulate education may also mitigate the ever-increasing problem of this disease.

The new definition of steatotic liver disease (SLD), as a broader concept, was a step forward in the increasing recognition of the substantial overlap between alcohol and cardiometabolic risk factors (CMRFs), in a continuum way. The spectrum of pathophysiological aspects, ranging from liver steatosis to fibrosis, has similarities in MASLD and ALD. Also, there is now considerable evidence that the association of metabolic dysfunction with increased alcohol consumption impacts on the risk of severe liver disease and prognosis. The new MetALD class, as recently proposed, shows clear differences in prognosis when comparing with MASLD and ALD groups. However, there is room for improvement, such as considering the role of previous alcohol intake, fluctuations of consumption over time, including binge drinking, refinement of alcohol assessment, and better understanding of the role of biomarkers. In summary, SLD is no doubt a significant improvement, but the new classification needs to be dynamic and adapting to patients needing frequent reassessment. Furthermore, it brings opportunities for research on the interaction between alcohol consumption and CMRFs.

Metabolic-associated liver disease is a growing public health crisis, with phenotypes from fatty liver to steatohepatitis, previously known as NASH (Non-Alcoholic SteatoHepatitis) and currently rebranded as MASH (Metabolic dysfunction-Associated SteatoHepatitis). Dysfunction in liver metabolism can progress to liver fibrosis, end stage cirrhosis and death. MASH (NASH) is associated with an increased risk of cardiovascular disease, elevation in serum lipids and Type 2 Diabetes Mellitus. There is now a US-approved drug to treat patients with NASH (MASH) under the FDA Accelerated Approval Pathway, which requires follow-up outcome studies to confirm clinical benefit or risk drug withdrawal by the agency. Despite extra-hepatic factors that contribute to MASH and complicate clinical trial design, reorganization of the FDA drug premarket review divisions, improvements to agency policies and procedures, as well as updates to the US Food, Drug & Cosmetic Act (FD&C Act) upon which FDA regulation is based, have provided new agency tools that facilitated such a drug approval to address the profound unmet medical need for patients with this metabolic-based liver disease. There is reason for hope that continued evolution of the regulatory process will lead to additional drug approvals, as well as the ability for clinical trial endpoints studying MASH treatments to include both liver-based and traditional metabolic measures, independent of the specific FDA review division. This initial NASH/MASH FDA approval has also opened the door for initiation of Combination Clinical Trials, where the approved drug is paired with an experimental drug with a different mechanism of action, to increase overall efficacy and potentially minimize risks. It is envisioned that future treatment of NASH/MASH will mirror what is currently observed with Type 2 Diabetes Mellitus practice patterns, where multiple drugs with different mechanisms of actions are used to optimize treatment benefit/risk in the selected patient populations.

The role of peridroplet mitochondria (PDM) in diseased liver, such as during the progression of metabolic dysfunction-associated steatohepatitis (MASH), remains unknown. We isolated hepatic cytoplasmic mitochondria (CM) and PDM from a mouse model of diet-induced MASLD/MASH to characterize their functions from simple steatosis to advanced MASH, using chow-fed mice as controls. Our findings show an inverse relationship between hepatic CM and PDM levels from healthy to steatosis to advanced MASH. Proteomics analysis revealed these two mitochondrial populations are compositionally and functionally distinct. We found that hepatic PDM are more bioenergetically active than CM, with higher pyruvate oxidation capacity in both healthy and diseased liver. Higher respiration capacity of PDM was associated with elevated OXPHOS protein complexes and increased TCA cycle flux. In contrast, CM showed higher fatty acid oxidation capacity with MASH progression. Transmission electron microscopy revealed larger and elongated mitochondria during healthy and early steatosis, which appeared small and fragmented during MASH progression. These changes coincided with higher MFN2 protein levels in hepatic PDM and higher DRP1 protein levels in hepatic CM. These findings highlight the distinct roles of hepatic CM and PDM in MASLD progression towards MASH.

Consumption of phytosterols is a nutritional strategy employed to reduce cholesterol absorption, but recent research shows that their biological activity might go beyond cholesterol reduction for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD), and novel phytosterol formulations, such as submicron dispersions, could improve these effects. We explored the therapeutic activity of phytosterols, either formulated as submicron dispersions of phytosterols (SDPs) or conventional phytosterol esters (PEs), in a mouse model of MAFLD. MAFLD was induced in mice by atherogenic diet (AD) feeding. The reversion of distorted serum and liver parameter values after a period of AD feeding was investigated after supplementation of the AD with SDPs, PEs, or a placebo (PT). Additionally, the metabolic parameters of fatty acid synthesis, fatty acid oxidation, and inflammation were studied to understand the mechanism of action of phytosterols. AD supplementation with SDPs was shown to reduce liver fat, along with showing a significant improvement in liver triglycerides (TGs), free fatty acids (FFAs), and liver cholesterol levels. These results were reinforced by the analyses of the liver steatosis scores, and liver histologies, where SDP intervention showed a consistent improvement. Treatment with PEs showed slighter effects in the same analyses, and no effects were observed with the PT treatment. Additionally, SDP intervention reversed, with a higher efficacy than PEs, the effect of AD on the serum levels of TGs, total- and LDL-cholesterol levels, and glucose levels. And, exceptionally, while SDP improved HDL-cholesterol serum levels, PEs did not show any effect on this parameter. We provide evidence for the therapeutical activity of phytosterols in MAFLD beyond the regulation of cholesterol levels, which is increased when the phytosterols are formulated as submicron dispersions compared to ester formulations.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prominent liver disease occurring in approximately 25% of the general population. As treatment, lifestyle modification is essential, but there are few reports on dietary patterns associated with MASLD except for the Mediterranean diet. This study examines dietary habits related to MASLD using the fatty liver index (FLI). Longitudinal analysis of a community-based cohort, the Nagahama Prospective Cohort for Comprehensive Human Bioscience, was performed. Dietary habits were assessed by a self-reported questionnaire on food intake frequency, and factor analysis was applied to identify dietary patterns. Multiple regression analysis was performed with baseline FLI or FLI after 5 y as the dependent variable and sex, age, and/or baseline FLI, and factor scores of each dietary pattern as simultaneous independent variables. The same analyses stratified by sex or body mass index (BMI) were also performed. Three thousand five hundred one participants were included. The 15 food items of the questionnaire were summarized into four dietary patterns. Dietary patterns rich in soybean products, vegetables, fish, fruits, and miso soup, which is characteristic of traditional Japanese diet, negatively correlated with FLI and FLI after 5 y (partial regression coefficient: -3.01 and -1.03, respectively; p<0.01 for both). The result was similar in sex-specific analysis and in BMI<23 kg/m2 group, when the participants were stratified according to BMI. Our results suggest that dietary patterns rich in soybean products, vegetables, fish, fruits, and miso soup are protective factors against MASLD especially in individuals with BMI<23 kg/m2.

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver, causing liver cell damage, increased inflammation, and weight gain. Despite its high prevalence, diagnosis and follow-up of the disease is difficult. Irisin, a slimming myokine produced in response to physical activity (PA), exhibits anti-inflammatory and anti-obesity effects. This study aimed to investigate changes in irisin levels, inflammation markers (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and myeloid differentiation factor-2 (MD2) levels in NAFLD, as well as anthropometric and routine biochemical parameters, by providing PA recommendations and nutrition education (NE) to individuals diagnosed with NAFLD over a period of 12 weeks.

The study included 62 patients diagnosed with NAFLD who did not use alcohol. They were divided into groups: PA, NE, both (NE + PA), and untreated (control) patients. Patients receiving NE were provided with 1-h NE sessions every 4 weeks for 12 weeks, and their personal information, nutritional status, 24-h retrospective food consumption record, and anthropometric measurements were recorded at the beginning (day 0) and end (week 12) of the study. The PA group was recommended aerobic walking for 30 min, 5 days a week. At the beginning (day 0) and end (week 12) of the study, patients' anthropometric and routine biochemical tests were conducted, and irisin, MD2, TNF-α, and IL-6 levels were measured using the ELISA method.

All groups were similar in demographic characteristics and dietary habits. After 12 weeks, there were no significant differences in biochemical parameters among the groups. Glucose levels increased in the untreated group but decreased in the PA and PA + NE groups compared to baseline, with a significant decrease in the PA group. Insulin levels significantly decreased in the NE group. The PA + NE group showed decreased aspartate aminotransferase (AST), gamma-glutamyl transferase, alkaline phosphatase, total cholesterol, low-density lipoprotein, and triglyceride levels and significant decrease in ALT levels. AST decreased significantly in the PA group while high-density lipoprotein increased significantly. There were no statistically significant differences between the groups in irisin, MD2, IL-6, and TNF-α levels. After 12 weeks, irisin levels significantly increased in nutrition and PA groups except the untreated group. There were no statistically significant differences in IL-6 and MD2 levels compared with baseline after 12 weeks. PA recommendations alone were not effective in observing significant changes in anthropometric measurements in individuals with NAFLD. It was detected that only nutritional recommendations provided a significant decrease in body fat ratio but were insufficient for the change in other anthropometric measurements. In the group where NE and PA were recommended together, a significant decrease in anthropometric measurements was found. The NE group significantly reduced their energy and carbohydrates (%EI) intake after 12 weeks of intervention compared with the baseline.

NE and PA recommendations led to improvements in liver-related biochemical parameters and significant reductions in anthropometric measurements among individuals with NAFLD. Moreover, patients receiving NE experienced a decrease in energy and carbohydrates intake as a percentage of total energy intake (%EI). Increased irisin levels in NE, PA, and NE + PA groups may have contributed to the decrease in body fat percentage.

Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD), emerges as major cause of morbidity and mortality globally, with chronic patients facing increased risk. Guidelines on MASLD management in primary care (PC) are limited. This study aimed to develop and evaluate a clinical care pathway for use in PC to improve MASLD screening and management, including early detection, communication and treatment, in three European countries (Greece, Spain, the Netherlands).

An international multidisciplinary panel of experts oversaw pathway development, which was designed as a two-step algorithm with defined and sequenced tasks. To evaluate algorithm implementation, a controlled pilot study was conducted. Patients at risk of MASLD were assigned to general practitioners (GPs) trained in algorithm implementation (active group) or usual care (control group) and followed for 4-8 weeks. Primary outcomes were the number of patients screened for MASLD, managed in PC and referred to specialists.

In this algorithm, patients with metabolic or liver dysfunction, confirmed MASLD or cardiovascular disease are screened with FIB-4 and classified as having risk of low-level (FIB-4 < 1.3), intermediate-level (1.3 ≤ FIB-4 < 2.67) or high-level MASLD (FIB-4 ≥ 2.67). The algorithm provides evidence-based tools to support GPs manage patients with risk of low-level MASLD in PC, coordinate linkage of patients with risk of high-level MASLD to specialists and refer patients with risk of intermediate-level MASLD for elastography (low-risk if <7.9 kPa or intermediate/high-risk if ≥7.9 kPa). During pilot evaluation, N = 37 participants were recruited in Spain (54.1% women, median age: 63 years). Significantly higher rates of patients in the active group (n = 17) than the control group (n = 20) were screened with FIB-4 (94.1% vs. 5.5%, p = 0.004). Patients in the active group received significantly more frequently a PC intervention for weight loss (70.6% vs. 10.0%, p < 0.001), alcohol regulation (52.9% vs. 0%, p < 0.001) and smoking cessation (29.4% vs. 0%, p = 0.005). In Greece no algorithm implementation was observed in either the active or control group, while the evaluation was not conducted in the Netherlands for logistic reasons.

This study provides evidence on the development and implementation of a new PC algorithm for MASLD screening and management. Variations among participating settings in algorithm implementation are indicative of context-specific particularities. Further research is necessary for integrating such pathways in tailored interventions to tackle this emerging public health issue.

The complement system, a coordinator and facilitator of the innate immune response, plays an essential role in maintaining host homeostasis. It promotes clearance of pathogen- and danger-associated molecular patterns, regulates adaptive immunity, and can modify various metabolic processes such as energy expenditure, lipid metabolism, and glucose homeostasis. In this review, we will focus on the intricate interplay between complement components and lipid metabolism. More precisely, we will display how alterations in the activation and regulation of the complement system affect pathological outcome in lipid-associated diseases, such as atherosclerosis, obesity, metabolic syndrome, age-related macular degeneration, and metabolic dysfunction-associated steatotic liver disease. In addition to that, we will present and evaluate underlying complement-mediated physiological mechanisms, observed both in vitro and in vivo. Our manuscript will demonstrate the clinical significance of the complement system as a bridging figure between innate immunity and lipid homeostasis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive liver disorder with a rising prevalence. It begins with lipid accumulation in hepatocytes and gradually progresses to Metabolic-associated steatohepatitis (MASH), fibrosis, cirrhosis, and potentially hepatocellular carcinoma (HCC). The pathophysiology of MASLD is complex and involves multiple factors, with oxidative stress playing a crucial role. Oxidative stress drives the progression of MASLD by causing cellular damage, inflammatory responses, and fibrosis, making it a key pathogenic mechanism. The Nuclear Factor Erythroid 2-Related Factor 2 / Heme Oxygenase-1 (Nrf2/HO-1) signaling axis provides robust multi-organ protection against a spectrum of endogenous and exogenous insults, particularly oxidative stress. It plays a pivotal role in mediating antioxidant, anti-inflammatory, and anti-apoptotic responses. Many studies indicate that activating the Nrf2/HO-1 signaling pathway can significantly mitigate the progression of MASLD. This article examines the role of the Nrf2/HO-1 signaling pathway in MASLD and highlights natural compounds that protect against MASLD by targeting Nrf2/HO-1 activation. The findings indicate that the Nrf2/HO-1 signaling pathway holds great promise as a therapeutic target for MASLD.

Ferroptosis, a form of regulated cell death characterized by lipid peroxidation and iron accumulation, has been implicated in the progression of metabolic-dysfunction-associated steatohepatitis (MASH) in obesity. This study investigated the role of ferroptosis in the development of hepatic steatosis and MASH in obese mice and assessed the therapeutic potential of ferrostatin-1, a ferroptosis inhibitor. C57BL/6J wild-type (n = 8) and ob/ob mice (n = 16) were maintained on a standard chow diet. Mice were divided into three groups that included C57BL/6 (n = 8), ob/ob (n = 8), and ob/ob + ferrostatin-1 (FER) (n = 8), with the latter group receiving an intraperitoneal injection of 5 μM/kg ferrostatin three times per week for eight weeks. Following treatment, serum and tissue samples were collected for analysis. Significant hepatic steatosis and increased lipogenesis markers were observed in ob/ob mice, which were restored to baseline levels in the ob/ob + FER group treated with ferrostatin-1. Elevated oxidative stress was indicated by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels in the ob/ob group, while glutathione peroxidase 4 (GPX4) activity was significantly reduced. Ferrostatin-1 treatment decreases MDA levels and restores GPX4 activity. Additionally, ferrostatin mitigates iron overload and promotes macrophage polarization from M1 to M2, thereby reducing liver inflammation and fibrosis. Ferrostatin treatment reversed mitochondrial dysfunction in ob/ob mice. Our findings revealed that ferroptosis plays a significant role in the progression of obesity to hepatic steatosis and MASH. Inhibiting ferroptosis using ferrostatin-1 effectively improves liver histology, reduces oxidative stress, normalizes lipogenesis, and modulates macrophage polarization. This study highlights the potential of targeting ferroptosis as a therapeutic strategy for obesity-related liver diseases, warranting further investigation in clinical settings.

Previous studies have demonstrated a significant association between serum vitamin A concentration and non-alcoholic fatty liver disease (NAFLD) development. However, the long-term prognostic implications of serum vitamin A in patients with NAFLD remain underexplored. This study aims to investigate whether there exists a correlation between serum vitamin A concentrations and overall mortality among subjects diagnosed with NAFLD.

To investigate the association between serum vitamin A concentrations and NAFLD outcomes, we conducted prospective cohort studies using data from the 1999-2006 and 2017-2018 National Health and Nutrition Examination Survey (NHANES). We utilized a multivariate Cox regression model to explore the relationship between serum vitamin A levels and all-cause mortality. Survival curves related to serum vitamin A were constructed using the Kaplan-Meier method. Additionally, the restricted cubic splines (RCS) method was applied to examine potential nonlinear relationships between serum vitamin A concentrations and all-cause mortality of NAFLD.

Over a median follow-up period of 10.3 years, a total of 1,399 all-cause deaths were recorded. The weighted average concentration of serum vitamin A was 61.48 ± 0.37 μg/dL. After adjusting for potential confounders, a significant U-shaped relationship was identified between serum vitamin A concentrations and the risk of all-cause mortality in NAFLD patients. This relationship was particularly pronounced in men and elderly individuals aged 60 to 85.

Our study reveals a significant non-linear relationship between serum vitamin A concentrations and the risk of all-cause mortality in patients with NAFLD. These findings underscore the importance of monitoring and maintaining optimal serum vitamin A levels to potentially improve survival outcomes in NAFLD patients.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most recent definition for steatotic liver disease associated with metabolic syndrome. The results of recent metabolic and observational studies suggest a potential beneficial effect of food-derived flavonoids in some chronic diseases, including MASLD. The study aims to evaluate the protective role of diet flavonoids in subjects with and without MASLD belonging to a cohort living in the South of Italy.

The study cohort comprised 1297 participants assessed in the NUTRIHEP cohort (2015-2018), divided into two groups, based on presence or absence of MASLD.

The results indicated statistically significant flavonoid consumption, showing a protective role against MASLD, at an optimal concentration of 165 mg/day, with an OR value of 0.63, (p = 0.001, 95% C.I.: 0.47; 0.83 t). The OR remained almost unchanged when the intake increased from 165 mg per day to 185 mg per day.

In conclusion, our study results show a protective role of flavonoids against MASLD. Consuming only 165 mg of flavonoids daily can activate this protective function, reducing the risk of MASLD.

Background/Objectives: The diverse effects of fructose and glucose on the progression of metabolic dysfunction-associated steatotic liver disease remain uncertain. This study investigated the effects, in animal models, of high-fat diets (HFDs) supplemented with either glucose or fructose. Methods: Six-week-old, male C57BL/6J mice were randomly allocated to four groups: normal diet (ND), HFD, HFD supplemented with fructose (30% w/v, HFD + Fru), and HFD supplemented with glucose (initially 30%, HFD + Glu). After 24 weeks, liver and plasma samples were gathered for analysis. In addition, 39 patients with obesity undergoing bariatric surgery with wedge liver biopsy were enrolled in the clinical study. Results: The HFD + Glu group consumed more water than did the HFD and HFD + Fru groups. Thus, we reduced the glucose concentration from 30% at baseline to 15% at week 2 and 10% starting from week 6. The HFD + Fru and HFD + Glu groups had a similar average caloric intake (p = 0.463). The HFD increased hepatic steatosis, plasma lipid levels, lipogenic enzymes, steatosis-related oxidative stress, hepatic inflammation, and early-stage liver fibrosis. Supplementation with fructose or glucose exacerbated liver damage, but no significant differences were identified between the two. The expression patterns of hepatic ceramides in HFD-fed mice (with or without supplemental fructose or glucose) were similar to those observed in patients with obesity and severe hepatic steatosis or metabolic dysfunction-associated steatohepatitis. Conclusions: Fructose and glucose similarly exacerbated liver damage when added to an HFD. Ceramides may be involved in the progression of hepatic lipotoxicity.

This investigation seeks to explore the correlation between nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs), and to to provide evidence for the prevention and treatment of CVDs.

This study utilized data from the Jinchang cohort platform, including 19,399 participants without pre-existing major CVDs. Based on the general population and gender stratification, Cox models were used to analyze the risk of NAFLD for CVDs. The combined effect of NAFLD and different obesity indicators on CVDs was analyzed by additive and multiplicative interaction models and subgroups.

There were 3129 NAFLD patients out of 19399 subjects, and 723 (23.11%) of them had the CVD. After adjusting for multiple confounding factors, the Cox model revealed a 1.17-fold increase in the risk of CVDs among patients with NAFLD compared to those without NAFLD. Moreover, there was no notable disparity in CVDs risk among most NAFLD patients at the same level of obesity. The results indicated no additive interaction between NAFLD and obesity concerning CVDs risk, but rather a positive multiplicative interaction. Using the normal population as a reference, it was found that people with both obesity and NAFLD significantly increased the risk of developing CVDs, with HRs and 95% CIs of 1.790 (1.508, 2.126), 1.356 (1.213, 1.517), and 1.807 (1.503, 2.174), respectively, for BMI, WC, and the combination of BMI and WC.

NAFLD and obesity are independent risk factors for CVDs. The synergy of obesity and NAFLD implies that NAFLD patients should control weight gain. Larger BMI and WC values may increase the CVDs risk for NAFLD patients, especially women.

In 2023, the concept of metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced as an alternative to non-alcoholic fatty liver disease (NAFLD). We aimed to assess the quantity and quality of skeletal muscle using each of these diagnostic classifications.

This cross-sectional study included 18 154 participants (11 551 [63.6%] men and 6603 [36.4%] women, mean age 53.0 ± 8.8). The participants were classified into four categories: neither steatotic liver disease (SLD), NAFLD only, MASLD only or both SLDs. An appendicular skeletal muscle mass adjusted for body mass index of <0.789 for men and <0.512 for women was defined as sarcopenia. The total abdominal muscle area (TAMA) at the L3 vertebral level was segmented into normal-attenuation muscle area (NAMA), low-attenuation muscle area and intermuscular/intramuscular adipose tissue. Myosteatosis was defined by a T-score < -1.0 of the NAMA/TAMA index, which was calculated by dividing the NAMA by the TAMA and multiplying by 100.

Using subjects with neither SLD as a reference, the multivariable-adjusted odds ratios (ORs) for sarcopenia were significantly increased in those with MASLD, with adjusted ORs (95% confidence interval [CI]) of 2.62 (1.94-3.54) in the MASLD-only group and 2.33 (1.92-2.82) in the both SLDs group, while the association was insignificant in those with NAFLD only (adjusted OR [95% CI]: 2.16 [0.67-6.94]). The OR for myosteatosis was also elevated in the MASLD groups, with an OR (95% CI) of 1.75 (1.52-2.02) in subjects with MASLD only and 1.70 (1.57-1.84) in those with both SLDs, while it was slightly decreased in subjects with NAFLD only (0.52 [0.29-0.95]).

Employing the MASLD concept rather than that of the NAFLD proved to be more effective in distinguishing individuals with reduced muscle mass and compromised muscle quality.

Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear.

Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics.

A sample of 11,509 participants with a mean age of 54.0 ± 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12), was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% CI 1.011-1.196; p = 0.026), but not incident AFib (log[FIB-4 index]) adjusted hazard ratio: 1.125 with 95% CI 0.943-1.342, p = 0.19). Elastic net regularized regression identified CCL20, DNER, and CXCL10 for prevalent AFib, and AXIN1, CXCL10, and Flt3L for the log(FIB-4 index) (per SD) as most important in common regulated proteins. The relationship between the FIB-4 index, the identified proteins, and AFib was relevant and reproduced at the 5-year follow-up for CXCL10 after adjusting for confounders (log[FIB-4 index] per SD - CXCL10 [per SD] adjusted β 0.160 with 95% CI 0.127-0.194, p <0.0001; CXCL10 [per SD] - AFib aOR 1.455 with 95% CI 1.217-1.741, p <0.0001), reproduced using the NFS and APRI, and corresponding to increased serum levels.

CXCL10 is linked to liver fibrosis, as determined by the FIB-4 index, and to prevalent AFib.

How elevated liver stiffness relates to atrial fibrillation in the general population remains to be clarified. We hypothesized that systemic inflammation against a background of liver fibrosis produced from metabolic dysfunction-associated steatotic liver disease (MASLD), is involved in the pathophysiology of atrial fibrillation. Using large-scale targeted proteomics, we found that CXCL10 is related to both liver fibrosis, as defined by the fibrosis-4 index, and to atrial fibrillation. These results can aid evidence-based drug development for patients with atrial fibrillation and MASLD-related liver fibrosis.

The incidence of obesity is rapidly increasing worldwide. Obesity-associated insulin resistance has long been established as a significant risk factor for obesity-related disorders such as type 2 diabetes and atherosclerosis. Insulin plays a key role in systemic glucose metabolism, with the liver, skeletal muscle, and adipose tissue as the major acting tissues. Insulin receptors and the downstream insulin signaling-related molecules are expressed in various tissues, including vascular endothelial cells, vascular smooth muscle cells, and monocytes/macrophages. In obesity, decreased insulin action is considered a driver for associated disorders. However, whether insulin action has a positive or negative effect on obesity-related disorders depends on the tissue in which it acts. While an enhancement of insulin signaling in the liver increases hepatic fat accumulation and exacerbates dyslipidemia, enhancement of insulin signaling in adipose tissue protects against obesity-related dysfunction of various organs by increasing the capacity for fat accumulation in the adipose tissue and inhibiting ectopic fat accumulation. Thus, this "healthy adipose tissue expansion" by enhancing insulin sensitivity in adipose tissue, but not in the liver, may be an effective therapeutic strategy for obesity-related disorders. To effectively address obesity-related metabolic disorders, the mechanisms of insulin resistance in various tissues of obese patients must be understood and drugs that enhance insulin action must be developed. In this article, we review the potential of interventions that enhance insulin signaling as a therapeutic strategy for obesity-related disorders, focusing on the molecular mechanisms of insulin action in each tissue.

RNA splicing is an essential post-transcriptional mechanism that facilitates the excision of introns and the connection of exons to produce mature mRNA, which is essential for gene expression and proteomic diversity. In the liver, precise splicing regulation is critical for maintaining metabolic balance, detoxification, and protein synthesis. This review explores the mechanisms of RNA splicing and the role of splicing factors, particularly in the context of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This review also highlights how RNA splicing dysregulation can lead to aberrant splicing and impact the progression of liver diseases such as MASLD, with a particular focus on Metabolic Dysfunction-Associated Steatohepatitis (MASH), which represents the advanced stage of MASLD. Recent advances in the clinical application of antisense oligonucleotides (ASOs) to correct splicing errors offer promising therapeutic strategies for restoring normal liver function. Additionally, the dysregulation of splicing observed in liver diseases may serve as a potential diagnostic marker, offering new opportunities for early identification of individuals more susceptible to disease progression. This review provides insights into the molecular mechanisms that govern splicing regulation in the liver, with a particular emphasis on MASLD, and discusses potential therapeutic approaches targeting RNA splicing to treat MASLD and related metabolic disorders.

The growing prevalence of NAFLD and its global health burden have provoked considerable research on possible diagnostic and therapeutic options for NAFLD. Although various pathophysiological mechanisms and genetic factors have been identified to be associated with NAFLD, its treatment remains challenging. In recent years, exosomes have attracted widespread attention for their role in metabolic dysfunctions and their efficacy as pathological biomarkers. Exosomes have also shown tremendous potential in treating a variety of disorders. With increasing evidence supporting the significant role of exosomes in NAFLD pathogenesis, their theragnostic potential has become a point of interest in NAFLD. Expectedly, exosome-based treatment strategies have shown promise in the prevention and amelioration of NAFLD in preclinical studies. However, there are still serious challenges in preparing, standardizing, and applying exosome-based therapies as a routine clinical option that should be overcome. Due to the great potential of this novel theragnostic agent in NAFLD, further investigations on their safety, clinical efficacy, and application standardization are highly recommended.

Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known.

We collected data from the National Health and Nutrition Examination Survey 2017-2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD.

A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092-11.249, P < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD (p < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases.

There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

Elevations in fructose consumption have been reported to contribute significantly to an increased incidence of obesity and metabolic diseases in industrial countries. Mechanistically, a high fructose intake leads to the dysregulation of glucose, triglyceride, and cholesterol metabolism in the liver, and causes elevations in inflammation and drives the progression of nonalcoholic fatty liver disease (NAFLD). A high fructose consumption is considered to be toxic to the body, and there are ongoing measures to develop pharmaceutical therapies targeting fructose metabolism. Although a large amount of work has summarized the effects fructose exposure within the intestine, liver, and kidney, there remains a gap in our knowledge regarding how fructose both indirectly and directly influences immune cell recruitment, activation, and function in metabolic tissues, which are essential to tissue and systemic inflammation. The most recent literature demonstrates that direct fructose exposure regulates oxidative metabolism in macrophages, leading to inflammation. The present review highlights (1) the mechanisms by which fructose metabolism impacts crosstalk between tissues, nonparenchymal cells, microbes, and immune cells; (2) the direct impact of fructose on immune cell metabolism and function; and (3) therapeutic targets of fructose metabolism to treat NAFLD. In addition, the review highlights how fructose disrupts liver tissue homeostasis and identifies new therapeutic targets for treating NAFLD and obesity.

Background and Aims: Screening for liver fibrosis presents a clinical challenge. This study aimed to explore a useful alternative method for assessing fibrosis risk among US adults at risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A liver stiffness score (LSS) model was proposed and tested using data from 3976 participants at possible risk of MASLD, obtained from the US National Health and Nutrition Examination Survey (NHANES). Results: The LSS model was developed using liver stiffness measurements, blood biochemistry, and body measurement data from 2414 NHANES participants at risk of MASLD, sampled between 2017 and 2020: LSS = exp(0.007035 × bodyweightkg - 0.1061 × raceblack1,0 + 0.183221 × diabetes1,0 + 0.008539 × ASTIU/L - 0.0018 × plateletcount1000cell/UL - 0.21011 × albuming/dL + 2.259087). The probability (P) of having fibrosis F3 + F4 is calculated as follows: P = 0.0091 × LSS2 - 0.0791 × LSS + 0.1933. The developed LSS model was tested on 1562 at-risk participants from the 2017-2018 cycle. The results showed that the LSS model achieved AUROC values of 0.79 and 0.78 for diagnosing cirrhosis (F4) and advanced fibrosis (F3 + F4) in the US population, respectively. It outperformed existing models such as NFS, FIB-4, SAFE, and FIB-3. For screening F3 + F4 fibrosis, the LSS model's top decile outperformed the NFS and FIB-4 models by 37.7% and 42.6%, respectively. Additionally, it showed superior performance compared to the waist circumference classification method by 29.5%. Conclusions: derived from an ethnically diverse population dataset, the LSS screening model, along with its probability equation, may offer clinicians a valuable alternative method for assessing the risk of liver fibrosis in the at-risk adult population.

Nonalcoholic fatty liver disease (NAFLD) is known to be associated with atherosclerosis. This study focused on upstream changes in the process by which NAFLD leads to atherosclerosis. The study aimed to confirm the association between NAFLD and the cardio-ankle vascular index (CAVI), an indicator of subclinical atherosclerosis, and explore metabolites involved in both by assessing 94 plasma polar metabolites.

A total of 928 Japanese community-dwellers (306 men and 622 women) were included in this study. The association between NAFLD and CAVI was examined using a multivariable regression model adjusted for confounders. Metabolites commonly associated with NAFLD and CAVI were investigated using linear mixed-effects models in which batch numbers of metabolite measurements were used as a random-effects variable, and false discovery rate-adjusted p-values were calculated. To determine the extent to which these metabolites mediated the association between NAFLD and CAVI, mediation analysis was conducted.

NAFLD was positively associated with CAVI (coefficients [95% Confidence intervals (CI)]=0.23 [0.09-0.37]; p=0.001). A total of 10 metabolites were involved in NAFLD and CAVI, namely, branched-chain amino acids (BCAAs; valine, leucine, and isoleucine), aromatic amino acids (AAAs; tyrosine and tryptophan), alanine, proline, glutamic acid, glycerophosphorylcholine, and 4-methyl-2-oxopentanoate. Mediation analysis showed that BCAAs mediated more than 20% of the total effect in the association between NAFLD and CAVI.

NAFLD was associated with a marker of atherosclerosis, and several metabolites related to insulin resistance, including BCAAs and AAAs, could be involved in the process by which NAFLD leads to atherosclerosis.

This study aims to investigate the relationship between Sodium Glucose Co-transporter-2 inhibitors (SGLT2i) treatment and fibrosis in patients with Metabolic dysfunction-associated steatotic liver disease (MASLD) combined with Type 2 Diabetes Mellitus (T2DM) and Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs).

A case-control study was conducted, involving 280 patients with MASLD combined with T2DM treated at the First Affiliated Hospital of Xinjiang Medical University from January 2014 to October 2023. Among these patients, 135 received SGLT2i treatment. The association between the Fibrosis-4 (FIB-4) index and the occurrence of MACCEs, as well as the association between the Aspartate Aminotransferase-to-Platelet Ratio Index (APRI) scores and MACCEs, were evaluated.

The FIB-4 index and APRI scores were significantly lower in the SGLT2i treatment group compared to the non-SGLT2i group (1.59 vs 1.25, P<0.001). SGLT2i treatment tended to reduce the occurrence of MACCEs compared to non-SGLT2i treatment (45.5% vs 38.5%, P=0.28). All patients who developed MACCEs in the non-SGLT2i treatment group had higher FIB-4 index (1.83 vs 1.35, P=0.003). Additionally, after SGLT2i treatment for a median duration of 22 months, patients showed significant reductions in blood glucose, APRI, and FIB-4 index.

SGLT2i treatment significantly reduces the occurrence of MACCEs and liver fibrosis in patients with MASLD combined with T2DM. The FIB-4 index may serve as a potential surrogate marker for predicting the occurrence of MACCEs.

This study aimed to assess the response patterns of circulating lipids to exercise and diet interventions in nonalcoholic fatty liver disease (NAFLD).

The 8.6-month four-arm randomized controlled study comprised 115 NAFLD patients with prediabetes who were assigned to aerobic exercise (AEx; n = 29), low-carbohydrate diet (Diet; n = 28), AEx plus low-carbohydrate diet (AED; n = 29), and nonintervention (NI, n = 29) groups. Hepatic fat content (HFC) was quantified by proton magnetic resonance spectroscopy. Serum lipidomic analytes were measured using liquid chromatography-mass spectrometry.

After intervention, the total level of phosphatidylcholine (PC) increased significantly in the AEx group ( P = 0.043), whereas phosphatidylethanolamine (PE) and triacylglycerol decreased significantly in the AED group ( P = 0.046 and P = 0.036, respectively), and phosphatidylserine decreased in the NI group ( P = 0.002). Changes of 21 lipid metabolites were significantly associated with changes of HFC, among which half belonged to PC. Most of the molecules related to insulin sensitivity belonged to sphingomyelin (40 of 79). Controlling for the change of visceral fat, the significant associations between lipid metabolites and HFC remained. In addition, baseline serum lipids could predict the response of HFC to exercise and/or diet interventions (PE15:0/18:0 for AED, area under the curve (AUC) = 0.97; PE22:6(4Z,7Z,10Z,13Z,16Z,19Z)/0:0 for AEx, AUC = 0.90; and PC14:1(9Z)/19:1(9Z) for Diet, AUC = 0.92).

Changes of lipidome after exercise and/or diet interventions were associated with HFC reductions, which are independent of visceral fat reduction, particularly in metabolites belonging to PC. Importantly, baseline PE could predict the HFC response to exercise, and PC predicted the response to diet. These results indicate that a circulating metabolomics panel can be used to facilitate clinical implementation of lifestyle interventions for NAFLD management.

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.

With the exploding prevalence of obesity, many children are at risk of developing nonalcoholic fatty liver disease. Using anthropometric and laboratory parameters, our study aimed to develop a model to quantitatively evaluate liver fat content (LFC) in children with obesity.

A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation cohort. The external validation cohort comprised 77 children. The assessment of liver fat content was performed using proton magnetic resonance spectroscopy. Anthropometry and laboratory metrics were measured in all subjects. B-ultrasound examination was carried out in the external validation cohort. The Kruskal-Wallis test, Spearman bivariate correlation analyses, univariable linear regressions and multivariable linear regression were used to build the optimal predictive model.

The model was based on indicators including alanine aminotransferase, homeostasis model assessment of insulin resistance, triglycerides, waist circumference and Tanner stage. The adjusted R2 of the model was 0.589, which presented high sensitivity and specificity both in internal [sensitivity of 0.824, specificity of 0.900, area under curve (AUC) of 0.900 with a 95% confidence interval: 0.783-1.000] and external validation (sensitivity of 0.918 and specificity of 0.821, AUC of 0.901 with a 95% confidence interval: 0.818-0.984).

Our model based on five clinical indicators was simple, non-invasive, and inexpensive; it had high sensitivity and specificity in predicting LFC in children. Thus, it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder, is closely associated with insulin resistance, obesity, and metabolic syndromes. A body of research has proposed that olive oil, a basic component of the Mediterranean diet with antioxidant and anti-inflammatory properties, may alleviate metabolic disturbances and retard the progression of NAFLD. We conducted a systematic review and meta-analysis to assess the effectiveness of olive oil intake in people with NAFLD. We systematically searched the major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Central Register of Controlled Trials), as well as grey literature sources, to identify randomized controlled trials (RCTs) investigating the effects of olive oil consumption on biochemical and anthropometric parameters of individuals with NAFLD. The quality of the studies was evaluated using the risk-of-bias tool 2.0 (RoB 2). The mean difference (MD) and the 95% confidence interval (CI) were calculated using fixed-effects and random-effects models. Seven RCTs involving 515 subjects were included in the analysis. In the random-effects model, no statistically significant differences were identified with respect to alanine transaminase (MD = -1.83 IU/L, 95% CI: -5.85, 2.19 IU/L, p = 0.37, I2 = 69%) and aspartate transaminase (MD = -1.65 IU/L, 95% CI: -4.48, 1.17 IU/L, p = 0.25, I2 = 72%) levels or waist circumference values (MD = -0.23 cm, 95% CI: -1.23, 0.76 cm, p = 0.65, I2 = 0%). However, a significant effect on body mass index was observed (MD = -0.57 kg/m2, 95% CI: -1.08, -0.06 kg/m2, p = 0.03, I2 = 51%) for subjects who received olive oil compared to those who received an alternative diet or placebo. The findings of the present meta-analysis suggest a modestly positive impact of olive oil intake on body weight in people with NAFLD.

In the realm of liver transplantation, accurately determining hepatic steatosis levels is crucial. Recognizing the essential need for improved diagnostic precision, particularly for optimizing diagnosis time by swiftly handling easy-to-solve cases and allowing the expert time to focus on more complex cases, this study aims to develop cutting-edge algorithms that enhance the classification of liver biopsy images. Additionally, the challenge of maintaining data privacy arises when creating automated algorithmic solutions, as sharing patient data between hospitals is restricted, further complicating the development and validation process. This research tackles diagnostic accuracy by leveraging novel techniques from the rapidly evolving field of quantum machine learning, known for their superior generalization abilities. Concurrently, it addresses privacy concerns through the implementation of privacy-conscious collaborative machine learning with federated learning. We introduce a hybrid quantum neural network model that leverages real-world clinical data to assess non-alcoholic liver steatosis accurately. This model achieves an image classification accuracy of 97%, surpassing traditional methods by 1.8%. Moreover, by employing a federated learning approach that allows data from different clients to be shared while ensuring privacy, we maintain an accuracy rate exceeding 90%. This initiative marks a significant step towards a scalable, collaborative, efficient, and dependable computational framework that aids clinical pathologists in their daily diagnostic tasks.

Metabolic dysfunction-associated steatohepatitis (MASH) is always accompanied with hepatic fibrosis that could potentially progress to liver cirrhosis and hepatocellular carcinoma. Employing a rat model, we evaluated the role of human placental extract (HPE) to arrest the progression of hepatic fibrosis to cirrhosis in patients with MASH. SHRSP5/Dmcr rats were fed with a high-fat and high-cholesterol diet for 4 weeks and evaluated for the development of steatosis. The animals were divided into control and treated groups and received either saline or HPE (3.6 ml/kg body weight) subcutaneously thrice a week. A set of animals were killed at the end of 6th, 8th, and 12th weeks from the beginning of the experiment. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic malondialdehyde (MDA), and glutathione content were measured. Immunohistochemical staining was performed for α-smooth muscle actin (α-SMA), 4-hydroxy-2-nonenal (4-HNE), collagen type I, and type III. Control rats depicted progression of liver fibrosis at 6 weeks, advanced fibrosis and bridging at 8 weeks, and cirrhosis at 12 weeks, which were significantly decreased in HPE-treated animals. Treatment with HPE maintained normal levels of MDA and glutathione in the liver. There was marked decrease in the staining intensity of α-SMA, 4-HNE, and collagen type I and type III in HPE treated rats compared with control animals. The results of the present study indicated that HPE treatment mediates immunotropic, anti-inflammatory, and antioxidant responses and attenuates hepatic fibrosis and early cirrhosis. HPE depicts therapeutic potential to arrest the progression of MASH towards cirrhosis.

Chronic liver diseases are a major global health concern.

this study investigated the links between medical, clinical, anthropometric, and dietary factors with dysfunction-associated steatotic liver disease (MASLD) in the Lebanese population using a case-control approach to uncover factors influencing visceral obesity, sarcopenia, and sarcopenic obesity.

a total of 120 participants (20-70 years old) were divided into case and control groups based on liver disease diagnosis. Patient information was gathered through a questionnaire encompassing demographics, medical history, and beverage consumption. Anthropometric and body composition data were collected in a clinical setting.

our findings indicated a clear association between the presence of MASLD and obesity, hypertension, and diabetes. The positive association with higher body mass index and all three conditions remained consistent even when data was stratified by case and control groups. A greater proportion of MASLD patients exhibited sarcopenic obesity. Furthermore, MASLD cases showed higher consumption of sugary beverages and a reduced intake of milk and water in their diets.

this study shed light on the health attributes and diets of the Lebanese population with liver diseases and suggested more research in this area and in a more ethnically diverse population.

Metabolic syndromes (MetS) and related cardiovascular diseases (CVDs) pose a serious threat to human health. MetS are metabolic disorders characterized by obesity, dyslipidemia, and hypertension, which increase the risk of CVDs' initiation and development. Although there are many availabile drugs for treating MetS and related CVDs, some side effects also occur. Considering the low-level side effects, many natural products have been tried to treat MetS and CVDs. A five-cyclic triterpenoid natural product, oleanolic acid (OA), has been reported to have many pharmacologic actions such as anti-hypertension, anti-hyperlipidemia, and liver protection. OA has specific advantages in the treatment of MetS and CVDs. OA achieves therapeutic effects through a variety of pathways, attracting great interest and playing a vital role in the treatment of MetS and CVDs. Consequently, in this article, we aim to review the pharmacological actions and potential mechanisms of OA in treating MetS and related CVDs.