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BRCC3 isopeptidase complex (BRISC) is a JAMM subfamily deubiquitinase that has been revealed to be required for optional activation of NLRP3 inflammasome and TLR4/NF-κB signaling pathway. BRISC plays an important role in lipopolysaccharide (LPS)/D-galactosamine-induced acute liver failure, while its functional contribution to alcoholic liver disease (ALD) is still unclear. In this study, we found that the expression of BRISC components was increased in liver tissues of alcoholic hepatitis (AH) animal models and patients with AH. Mice lacking either the scaffold subunit ABRO1 or the catalytic subunit BRCC3 showed attenuated liver steatosis, inflammation, and liver injury compared to control mice after chronic plus binge ethanol feeding. Moreover, pharmacological inhibition of BRISC activity by a BRISC inhibitor thiolutin potently protected mice from ALD development. Preliminary mechanistical studies showed that BRISC deficiency did not directly affect alcohol-induced hepatocyte injury or the translocation of LPS through the damaged gut mucosa after ethanol feeding, but prevented alcohol-induced NLRP3 inflammasome activation in liver. Collectively, our work revealed a previously unknown role of BRISC in ALD and suggested that BRISC may serve as a promising therapeutic target for ALD treatment. [ABSTRACT FROM AUTHOR]

Objective: Metabolic dysfunction-associated fatty liver disease (MAFLD) and nephrolithiasis are two common metabolic diseases, but their relationship has not yet been thoroughly studied. Therefore, this study aimed to explore the association between MAFLD and nephrolithiasis and to assess the effect of MAFLD on the risk of nephrolithiasis. Materials and methods: This cross-sectional study included 96,767 adults from China. All participants underwent medical examinations, including physical examinations, medical history tests, and laboratory tests. Based on ultrasound examination, participants were divided into MAFLD and non-MAFLD groups, and the severity of liver steatosis was determined based on ultrasound images. The relationship between MAFLD and nephrolithiasis was analyzed using a multivariate logistic regression model and subgroup analysis was performed. Results: The proportion of participants with MAFLD was significantly higher in the nephrolithiasis group compared to the non-nephrolithiasis group (47.70% vs. 30.45%, P < 0.001). Multivariate logistic regression analysis showed a significant positive association between MAFLD and nephrolithiasis (adjusted OR =1.38, 95% CI : 1.29 to 1.47). Subgroup analyses indicated that, even after accounting for various factors such as age, diabetes, hypertension, obesity, lipid profiles, and renal function, the positive association between MAFLD and an increased risk of nephrolithiasis remained consistent. Further subgroup analysis revealed that in male patients with MAFLD, the risk of nephrolithiasis increased progressively with increasing severity of liver steatosis. The adjusted multivariable odds ratios were 1.43 (95% CI : 1.33 to 1.53) for mild, 1.48 (95% CI : 1.32 to 1.67) for moderate, and 1.94 (95% CI : 1.47 to 2.58) for severe hepatic steatosis. Conclusions: This study found a significant positive association between MAFLD and nephrolithiasis. The risk of nephrolithiasis in males with MAFLD increased substantially with increasing severity of liver steatosis. Therefore, it is essential to strengthen prevention and screening for nephrolithiasis in individuals with MAFLD. More research is needed to elucidate the physiological and pathological mechanisms between MAFLD and nephrolithiasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: US tools to quantify hepatic steatosis have recently been made clinically available by different manufacturers, but comparative data on their consistency are lacking. Objective: US tools to quantify hepatic steatosis have recently been made clinically available by different manufacturers, but comparative data on their consistency are lacking. The aim of our study was to compare the diagnostic consistency for evaluating hepatic steatosis by two different US techniques, hepatorenal index by B-mode Ratio and attenuation coefficient by attenuation imaging (ATI). Methods: Patients with suspicion or previously diagnosed of metabolic dysfunction-associated steatotic liver disease (MASLD) who attended fatty liver consulting room from June 2023 to September 2023 were prospectively recruited. Patients underwent two different US techniques of B-mode Ratio and ATI, and laboratory test were collected. According to previously proposed cut-off values, B-mode Ratio ≥ 1.22, 1.42, 1.54, and ATI ≥ 0.62, 0.70, and 0.78 dB/cm/MH were used for assessing of mild, moderate, and severe hepatic steatosis, respectively. Kappa consistency test was used to evaluate the consistency of hepatic steatosis. Results: A total of 62 patients were enrolled, including 44 males (71.0%) with an age of (41 ± 13) years and a body mass index of (27.0 ± 3.5) kg/m2. In the hyperlipidemia group, the B-mode Ratio and ATI were significantly higher than those in the non-hyperlipidemia group, with values of 1.68 ± 0.39 vs. 1.28 ± 0.35 (p = 0.001) and 0.74 ± 0.12 dB/cm/MH vs. 0.64 ± 0.11 dB/cm/MH (p = 0.005), respectively. The correlation coefficient between B-mode Ratio and ATI was 0.732 (p < 0.001). Using B-mode Ratio and ATI as diagnostic criteria for MASLD, the proportion of patients with MASLD was 79% and 82%, respectively. The Kappa coefficient for assessing MASLD was 0.90 (p < 0.001). Furthermore, these two different US techniques were used for grading hepatic steatosis, with no, mild, moderate, and severe steatosis accounting for 21%, 18%, 13%, and 48%, as well as 18%, 29%, 22%, and 31%, respectively. The linear weighted Kappa coefficient for staging hepatic steatosis was 0.78 (95% confidence interval: 0.68–0.87, p < 0.001). Conclusion: The non-invasive methods of two different US techniques based on B-mode Ratio and ATI have good consistency for evaluating hepatic steatosis, and can be used for large-scale community screening. [ABSTRACT FROM AUTHOR]

To investigate the changes in liver stiffness and immune-inflammatory markers associated with obesity and the degree of hepatic steatosis in obese children and adolescents. A total of 76 obese children and adolescents aged 6–18 years, with body mass index percentiles >95th, were included in the study. Patients with metabolic syndrome, diabetes mellitus, and chronic liver disease were excluded. A control group of 44 patients of healthy and normal-weight children was included. Laboratory values from the past month were analyzed using patient records. Shear wave elastography and ultrasound examinations were performed on a single device by the same experienced radiologist. The systemic immune-inflammation index and pan-immune inflammation values were significantly higher in obese patients with hepatic steatosis compared to obese patients without hepatic steatosis (p <0.001). Liver stiffness values were significantly higher in steatotic patients compared to nonsteatotic patients (p <0.001). A significant difference was observed between hepatic steatosis grades in terms of immune-inflammation index and pan-immune inflammation value values (p <0.001). There was a strong, positive, statistically significant correlation between liver stiffness and immune-inflammation index and pan-immune inflammation value (p <0.05). Immune-inflammatory biomarkers and shear wave elastography may provide valuable insights into the diagnosis and follow-up of inflammation and fibrosis in the evaluation of hepatic steatosis in obese children and adolescents. [ABSTRACT FROM AUTHOR]

Background/Objectives: The characterization of patients with inflammatory bowel disease (IBD) and type 2 diabetes mellitus (T2DM) as a new group has not been well detailed. This study aimed to evaluate the impact of T2DM on IBD progression and analyze the prevalence of steatotic liver disease and liver damage in these patients. Methods: Through a retrospective case–control study, we compared severe IBD occurrence in patients with both IBD-T2DM (cases) versus those with IBD alone (controls). Among 1047 medical records, 79 IBD-T2DM patients were selected and compared to 308 controls in a 1:4 ratio. Severe IBD was defined by variables such as surgery, target therapy, corticosteroid use, and hospitalization. Liver damage was assessed using Fib-4 (>1.3), and hepatic steatosis was evaluated by imaging. Results: There was no significant difference in severe disease rates (59.5% vs. 59.7%; p = 0.97). IBD-T2DM patients had higher rates of hepatic steatosis (62.9% vs. 27.2%; p < 0.0001) and liver damage (55.4% vs. 26.6%; p < 0.0001). IBD-T2DM patients used more corticosteroids (p < 0.0001) and fewer anti-TNF-alpha drugs (p = 0.007). The median age at diagnosis was higher in IBD-T2DM patients (48 vs. 32; p < 0.0001). In Crohn's disease, 24.3% of IBD-T2DM patients had exclusive colonic involvement compared to 5% in the IBD-only group (p = 0.003). Conclusions: T2DM was not associated with worse IBD progression, but was linked to increased liver steatosis and damage. Differences such as age of onset, colonic involvement, and liver damage suggest that IBD-T2DM patients could configure a special population worthy of further studies. [ABSTRACT FROM AUTHOR]

Purpose: Early detection and quantitative evaluation of liver steatosis are crucial. Therefore, this study investigated a method for classifying ultrasound images to fatty liver grades based on echo-envelope statistics (ES) and convolutional neural network (CNN) analyses. Methods: Three fatty liver grades, i.e., normal, mild, and moderate-to-severe, were defined using the thresholds of the magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF). There were 10 cases of each grade, totaling 30 cases. To visualize the texture information affected by the deposition of fat droplets within the liver, the maps of first- and fourth-order moments and the heat maps formed from both moments were employed as parametric images derived from the ES. Several dozen to hundreds of regions of interest (ROIs) were extracted from the liver region in each parametric image. A total of 7680 ROIs were utilized for the transfer learning of a pretrained VGG-16 and classified using the transfer-learned VGG-16. Results: The classification accuracies of the ROIs in all types of the parametric images were approximately 46%. The fatty liver grade for each case was determined by hard voting on the classified ROIs within the case. In the case of the fourth-order moment maps, the classification accuracy of the cases through hard voting mostly increased to approximately 63%. Conclusions: The formation of parametric images derived from the ES and the CNN classification of the parametric images were proposed for the quantitative diagnosis of liver steatosis. In more than 60% of the cases, the fatty liver grade could be estimated solely using ultrasound images. [ABSTRACT FROM AUTHOR]

Background: The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has plagued the general population of the world, which has revised the nomenclature of nonalcoholic fatty liver disease (NAFLD). Transient elastography is one of the key screening methods for MASLD to evaluate the presence of fat and fibrosis in the liver. Materials and Methods: This was a cross-sectional, observational study performed at the single diabetology center of Ahmedabad, in participants aged 18 years and above, and having any one cardio-metabolic risk factors of type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, or obesity. Their lipid, sugar, and transient elastography parameters; controlled attenuation parameter (CAP), and liver stiffness measurement (LSM) were recorded. Results: In data of 141 participants, the presence of co-morbid conditions such as obesity (80.14%) was most common, followed by T2DM in 45.4%, while 79.5% had steatosis (> S0) and 27.6% had fibrosis (> F0/F1). Co-morbid conditions like higher weight and history of myocardial infarction (MI) were the major risk factors associated with increased CAP score, whereas higher weight and glycosylated hemoglobin (HbA1c) were the risk factors for increased LSM values. Fibrosis index-4 score has a poor correlation with the LSM and CAP score individually. Conclusion: The distribution of liver fibrosis and steatosis assessed using the CAP and LSM score, in MASLD individuals, is prevalent among patients with a history of MI and excess weight; while higher HbA1c is significantly associated with LSM score only. [ABSTRACT FROM AUTHOR]

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers of liver fibrosis and hematological parameters in the course of non-alcoholic fatty liver disease (NAFLD). Methods: Two hundred and seven persons were included in the survey: 97 with NAFLD and 110 healthy controls. Serological concentrations of miR-126-3p, miR-197-3p, and miR-1-3p were measured in all participants. Direct indices of liver fibrosis [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin] together with indirect markers (AAR, APRI, FIB-4 and GPR) were also evaluated. The assessment of hematological parameters concerned: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red blood cell distribution width (RDW), MPV to platelet (PLT) ratio (MPR), RDW to PLT ratio (RPR), neutrophil to lymphocyte (LYM) ratio (NLR), PLT to LYM ratio (PLR) and RDW to LYM ratio (RLR). Additionally, the NAFLD fibrosis score and BARD score were applied. Results: The concentration of miR-126-3p and miR-1-3p was higher, and miR-197-3p was lower in the NAFLD group (p < 0.0001). miR-197-3p correlated notably with hematological indices: negatively with PDW (p < 0.05) and positively with PLR (p < 0.05). Conclusions: Significant correlations between miRNA molecules and hematological markers in the course of NAFLD indicate inflammation as a potential background and create new possibilities for a diagnostic approach. [ABSTRACT FROM AUTHOR]

Background: The 1-h post-load plasma glucose was proposed to replace the current OGTT criteria for diagnosing prediabetes/diabetes. However, it remains unclear whether it is superior in identifying progressive metabolic dysfunction-associated steatotic liver disease (MASLD), and thus we aimed to clarify this issue. Methods: Consecutive Asian participants (non-MASLD, n = 1049; MASLD, n = 1165) were retrospectively enrolled between June 2012 and June 2024. CT was used to quantify liver steatosis, while the serum liver fibrotic marker was used to evaluate liver fibrosis. Results: Compared with those with normal levels of both 1-h post-glucose (1hPG) and 2-h post-glucose (2hPG), patients with MASLD showed a significant positive association between elevated 1hPG levels and moderate to severe liver steatosis (odds ratio [OR] = 2.19, 95% confidence interval [CI]: 1.13–4.25, p = 0.02]. Elevated levels of both 1hPG and 2hPG were associated with an increased risk of liver injury (OR = 2.03, 95% CI: 1.44–2.86, p < 0.001). Elevated 2hPG levels with or without elevated 1hPG levels were associated with liver fibrosis (OR = 1.99, 95% CI: 1.15–3.45, p < 0.001; OR = 2.72, 95% CI: 1.79–4.11, p < 0.001, respectively). Additionally, either 1hPG or 2hPG levels were associated with atherosclerosis, revealing significant dose-dependent associations between glucose status and atherosclerosis risk (OR = 2.77, 95% CI: 1.55–4.96, p < 0.001 for elevated 1hPG; OR = 2.98, 95% CI = 1.54–5.78, p = 0.001 for elevated 2hPG; OR = 2.41, 95% CI = 1.38–4.21, p = 0.001 for elevated levels of both 1hPG and 2hPG). The areas under the ROC for predicting steatosis, liver injury, liver fibrosis, and atherosclerosis were 0.64, 0.58, 0.58, and 0.64 for elevated 1hPG (all p < 0.05) and 0.50, 0.60, 0.56, and 0.62 for elevated 2hPG (all p < 0.05), respectively. Conclusions: These findings underscore the necessity for clinicians to acknowledge that the screening and management of MALSD requires the monitoring of 1hPG levels. [ABSTRACT FROM AUTHOR]

Abstract Background While the associations between pediatric non-obese metabolic dysfunction-associated fatty liver disease (MAFLD) and multiple diagnostic biomarkers are well-established, the role of a broader range of blood-based, urine-based, and body composition-based biomarkers for monitoring MAFLD are needed. Methods A pediatric cohort was established in Wuxi, China. We measured body composition biomarkers, blood-based and urine-based biomarkers, and liver stiffness in participants to diagnose MAFLD and identify alternative and novel potential biomarkers for MAFLD. Body mass index (BMI), high-density lipoprotein cholesterol (HDLC), triglycerides, glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist perimeter were used as MAFLD diagnostic biomarkers. To identify alternative biomarkers, we performed correlation analysis to determine biomarkers exhibited strong correlation (|r| > 0.8, p-value

Abstract Background US tools to quantify hepatic steatosis have recently been made clinically available by different manufacturers, but comparative data on their consistency are lacking. Objective US tools to quantify hepatic steatosis have recently been made clinically available by different manufacturers, but comparative data on their consistency are lacking. The aim of our study was to compare the diagnostic consistency for evaluating hepatic steatosis by two different US techniques, hepatorenal index by B-mode Ratio and attenuation coefficient by attenuation imaging (ATI). Methods Patients with suspicion or previously diagnosed of metabolic dysfunction-associated steatotic liver disease (MASLD) who attended fatty liver consulting room from June 2023 to September 2023 were prospectively recruited. Patients underwent two different US techniques of B-mode Ratio and ATI, and laboratory test were collected. According to previously proposed cut-off values, B-mode Ratio ≥ 1.22, 1.42, 1.54, and ATI ≥ 0.62, 0.70, and 0.78 dB/cm/MH were used for assessing of mild, moderate, and severe hepatic steatosis, respectively. Kappa consistency test was used to evaluate the consistency of hepatic steatosis. Results A total of 62 patients were enrolled, including 44 males (71.0%) with an age of (41 ± 13) years and a body mass index of (27.0 ± 3.5) kg/m2. In the hyperlipidemia group, the B-mode Ratio and ATI were significantly higher than those in the non-hyperlipidemia group, with values of 1.68 ± 0.39 vs. 1.28 ± 0.35 (p = 0.001) and 0.74 ± 0.12 dB/cm/MH vs. 0.64 ± 0.11 dB/cm/MH (p = 0.005), respectively. The correlation coefficient between B-mode Ratio and ATI was 0.732 (p

ObjectiveMetabolic dysfunction-associated fatty liver disease (MAFLD) and nephrolithiasis are two common metabolic diseases, but their relationship has not yet been thoroughly studied. Therefore, this study aimed to explore the association between MAFLD and nephrolithiasis and to assess the effect of MAFLD on the risk of nephrolithiasis.Materials and methodsThis cross-sectional study included 96,767 adults from China. All participants underwent medical examinations, including physical examinations, medical history tests, and laboratory tests. Based on ultrasound examination, participants were divided into MAFLD and non-MAFLD groups, and the severity of liver steatosis was determined based on ultrasound images. The relationship between MAFLD and nephrolithiasis was analyzed using a multivariate logistic regression model and subgroup analysis was performed.ResultsThe proportion of participants with MAFLD was significantly higher in the nephrolithiasis group compared to the non-nephrolithiasis group (47.70% vs. 30.45%, P < 0.001). Multivariate logistic regression analysis showed a significant positive association between MAFLD and nephrolithiasis (adjusted OR=1.38, 95% CI: 1.29 to 1.47). Subgroup analyses indicated that, even after accounting for various factors such as age, diabetes, hypertension, obesity, lipid profiles, and renal function, the positive association between MAFLD and an increased risk of nephrolithiasis remained consistent. Further subgroup analysis revealed that in male patients with MAFLD, the risk of nephrolithiasis increased progressively with increasing severity of liver steatosis. The adjusted multivariable odds ratios were 1.43 (95% CI: 1.33 to 1.53) for mild, 1.48 (95% CI: 1.32 to 1.67) for moderate, and 1.94 (95% CI: 1.47 to 2.58) for severe hepatic steatosis.ConclusionsThis study found a significant positive association between MAFLD and nephrolithiasis. The risk of nephrolithiasis in males with MAFLD increased substantially with increasing severity of liver steatosis. Therefore, it is essential to strengthen prevention and screening for nephrolithiasis in individuals with MAFLD. More research is needed to elucidate the physiological and pathological mechanisms between MAFLD and nephrolithiasis.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver condition in children, underscoring the urgent need for non-invasive markers for early detection in this population.MethodsWe utilized survey data from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 regarding liver ultrasound transient elastography (LUTE) for the diagnosis of NAFLD (dependent variable), and used multiple logistic regression models to explore the association between weight-adjusted waist circumference index (WWI) and the prevalence of NAFLD in US adolescents. Smoothing curves and threshold effect analyses were used to assess the non-linear association between the independent variables and the dependent variable. Subgroup analysis was conducted to pinpoint particularly susceptible subgroups within our study cohort of 1,711 participants.ResultsOur findings indicated a positive correlation between WWI and NAFLD scores. Adjusting for all covariates revealed a significant association between increased WWI and the presence of NAFLD, with an odds ratio of 3.37 (95% CI: 2.74, 4.15). This association proved stronger than those observed with waist circumference, body mass index, and NAFLD. Stratifying WWI into quartiles showed a clear and strong positive correlation (P for trend < 0.0001). The results of smoothing curves and threshold effect analysis showed a non-linear relationship between WWI and NAFLD (LLR < 0.001). Notably, for WWI values below 10.65, a significant correlation was observed (OR = 5.25, 95% CI: 3.77,7.31). Additionally, our subgroup analysis revealed that WWI and NAFLD were associated more positively among male participants aged 16 years and older.ConclusionWWI is positively correlated with NAFLD in American adolescents and offers a straightforward and cost-effective method for identifying hepatic steatosis. The findings highlight the importance of focusing on individuals with a WWI below 10.65, where the risk of NAFLD increases. Priority should be given to the male adolescent population aged 16 and above.

Background: The inheritance of the short SLC6A4 allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert-/-) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD). Growing evidence suggests the significance of hepatic regulatory mechanisms in the neurobiology of central nervous system disorders, supporting the ‘liver-brain’ concept. However, the relationship between aberrant behavior and hepatic alterations under conditions of SERT deficiency remains poorly investigated. Methods: One-year-old female Sert-/- mice and their wild-type (WT) littermates were subjected to a control diet (CD) or the WD for a duration of three weeks. The WD had a higher caloric content and was characterized by an elevated saturated fat content (21%) compared to the CD (4.5%) and contained 0.2% cholesterol. Mice were evaluated for anxiety-like behavior, exploration and locomotor activity in the open field test, as well as glucose tolerance and histological indicators of hepatic steatosis. Hepatic pro-inflammatory and metabolism-related gene expression and markers of nitrosative stress, were analyzed utilizing real-time polymerase chain reaction (RT-PCR) and correlated with behavioral and histological outcomes. Results: In comparison to unchallenged mice, Sert-/-/WD mutants, but not the WT/WD group, had increased locomotion and anxiety-like behavior, increased hepatic steatosis, and elevated expression of insulin receptor B and pro-inflammatory cytokines interleukin-1β (Il-1β) and Tnf, as well as decreased expression of leptin receptor B. The two genotypes displayed distinct gene expression patterns of nitric oxide (NO)-related molecules inducible NO synthase (iNos) and arginase (Arg2), insulin receptor-related signaling factors: cluster of differentiation 36 (Cd36), ecto-nucleotide pyrophosphatase/phosphodiesterase (Enpp), protein tyrosine phosphatase N1 (Ptpn1), cytochrome P450 omega-hydroxylase 4A14 (Cyp4a14), acyl-CoA synthetase 1 (Acsl1) and phosphatase and tensin homolog (Pten). Furthermore, there were profound differences in correlations between molecular, histological, and behavioral measurements across the two genotypes. Conclusions: Our findings suggest that the genetic deficiency of SERT results in abnormal hepatic pro-inflammatory and metabolic adaptations in response to WD. The significant correlations observed between behavioral measures and pro-inflammatory and metabolic alterations in WD-fed mice suggest the importance of liver-brain interactions and their role in the aberrant behaviors exhibited by Sert-/- mutants. This study presents the first evidence that altered liver functions are associated with pathological behaviors arising from genetic SERT deficiency.

Background: Asymptomatic liver steatosis constitutes an emerging issue worldwide. Therefore, we decided to explore relationships between selected types of microRNAs (miRNAs), serological markers of liver fibrosis and hematological parameters in the course of non-alcoholic fatty liver disease (NAFLD). Methods: Two hundred and seven persons were included in the survey: 97 with NAFLD and 110 healthy controls. Serological concentrations of miR-126-3p, miR-197-3p, and miR-1-3p were measured in all participants. Direct indices of liver fibrosis [procollagen I carboxyterminal propeptide (PICP), procollagen III aminoterminal propeptide (PIIINP), platelet-derived growth factor AB (PDGF-AB), transforming growth factor-α (TGF-α) and laminin] together with indirect markers (AAR, APRI, FIB-4 and GPR) were also evaluated. The assessment of hematological parameters concerned: mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red blood cell distribution width (RDW), MPV to platelet (PLT) ratio (MPR), RDW to PLT ratio (RPR), neutrophil to lymphocyte (LYM) ratio (NLR), PLT to LYM ratio (PLR) and RDW to LYM ratio (RLR). Additionally, the NAFLD fibrosis score and BARD score were applied. Results: The concentration of miR-126-3p and miR-1-3p was higher, and miR-197-3p was lower in the NAFLD group (p < 0.0001). miR-197-3p correlated notably with hematological indices: negatively with PDW (p < 0.05) and positively with PLR (p < 0.05). Conclusions: Significant correlations between miRNA molecules and hematological markers in the course of NAFLD indicate inflammation as a potential background and create new possibilities for a diagnostic approach.

Background: Metabolic-associated fatty liver disease (MAFLD) is a prevalent condition with significant health and economic burdens. Dietary interventions, such as intermittent fasting (IF) and low-calorie diets (LCD), have shown promise in managing MAFLD, but their comparative efficacy remains unclear., Methods: This 10-month, parallel, single-blind randomized controlled trial compared the effects of a 16:8 IF diet with an LCD on 52 patients with MAFLD. Anthropometric, biochemical, liver enzyme, steatosis, fibrosis, inflammatory, and oxidative status parameters were assessed before and after the interventions., Results: Both diets led to improvements in anthropometric measures and liver enzyme levels, with no significant differences between groups. However, the LCD group showed superior outcomes in reducing liver steatosis (-52.40 vs -44.63 dB/m; P < 0.001) and fibrosis (-0.74 vs -0.004 Kpa; P = 0.01) compared to the IF group. LCD also led to a significant decrease in serum triglycerides (-24.08 vs 11.22 mg/dL; P = 0.02), while neither intervention significantly affected inflammatory markers or oxidative status., Conclusion: While both IF and LCD can be effective in managing MAFLD, LCD may offer additional benefits in terms of liver fat reduction and improvement in certain lipid parameters. These findings highlight the complexity of dietary interventions in MAFLD and the need for personalized approaches., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cancer, obesity, Inflammation, NAFLD, supplement., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Objective: We reviewed the evidence on the impact of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis on mortality, functional dependence, and recurrence after acute ischemic stroke (AIS)., Methods: This PROSPERO registered review searched PubMed, Embase, CENTRAL, and Web of Science databases from inception of databases to 30 th July 2023 for studies comparing outcomes of AIS based on the presence of NAFLD and liver fibrosis. Adjusted data on mortality, functional dependence and risk of recurrent AIS was pooled to obtain odds ratio (OR) with 95% confidence intervals (CI) in a random-effects model., Results: Ten studies were included. Descriptive analysis showed conflicting effects of NAFLD on AIS outcomes with some studies showing better functional outcomes with the presence of NAFLD. Meta-analysis showed that the presence of liver fibrosis was associated with a significantly increased risk of mortality (OR: 2.22 95% CI: 1.02-4.86 I 2 =92%) and functional dependence (OR: 1.89 95% CI: 1.27-2.82 I 2 =53%) as compared to no fibrosis. Meta-analysis found that liver fibrosis did not increase the risk of recurrent AIS (OR: 1.32 95% CI: 0.74-2.37 I 2 =74%)., Conclusion: Scant evidence exists for the effect of NAFLD and liver fibrosis on AIS outcomes. A paradoxical effect of NAFLD on functional outcomes has been noted which needs confirmation by future studies. Liver fibrosis was found to increase the risk of mortality and functional dependence in AIS., (Copyright: © Pakistan Journal of Medical Sciences.)

Background and Aims: The prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease has increased in parallel with a rise in consumption of ultra-processed foods (UPF), but little is known about their association., Methods: We cross-sectionally examined associations of UPF with hepatic steatosis and fibrosis in 2458 (mean age 54 years; 55.9 % women) community-dwelling adults who completed vibration-controlled transient elastography and a food frequency questionnaire. Dietary intake was categorized into levels of food processing via the NOVA system. We used multivariable-adjusted logistic regression models to evaluate the association of energy-adjusted UPF intake (per 1-SD unit and by quintile) with clinical hepatic steatosis (Controlled Attenuation Parameter [CAP]≥ 290 dB/m) and fibrosis (Liver Stiffness Measurement [LSM] ≥ 8.2 kPa) and tested for linear trends of UPF intake with CAP and LSM. We adjusted for age, sex, smoking, alcohol intake, physical activity, and intake of minimally processed foods. Additional models adjusted for diet quality index or body mass index (BMI)., Results: Higher intake of UPF was directly associated with higher odds of hepatic steatosis (Odds Ratio 1.33 [95 % Confidence Interval 1.21, 1.46] per standard deviation increase). UPF intake and CAP had a dose-response relation (P trend <0.001). There were 2.50 times higher odds of hepatic steatosis (Confidence Interval 1.81, 3.45) with a 19.49 (standard error: 3.73) unit increase in CAP (P < 0.001) when comparing quintile 5 to quintile 1 of UPF consumption. Higher UPF was not significantly associated with hepatic fibrosis. Adjustment for BMI attenuated the strength of all UPF-hepatic associations., Conclusions: UPF consumption was positively associated with hepatic steatosis. Longitudinal studies are needed to assess whether lowering consumption of UPF can decrease odds of hepatic fibrosis., Competing Interests: Declaration of competing interest Michelle T. Long is employed full time by Novo Nordisk A/S. All other authors have no relevant conflicts of interest., (Copyright © 2025 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Orosomucoid (ORM) is an important hepatokine that regulates metabolism. Previous report showed that isoform ORM2 but not ORM1 could downregulate lipogenic genes and ameliorate hepatic steatosis in obese mice, thereby categorizing ORM2 as a promising candidate for therapeutic intervention in nonalcoholic fatty liver disease (NAFLD). However, our previous studies found that mice lacking ORM1 gradually developed an obese phenotype with severe hepatic steatosis at the age of 24 weeks. Consequently, it remains imperative to further investigate the precise role of ORM1 in the context of NAFLD. The current study aims to assess the function and therapeutic prospects of ORM1 in NAFLD models induced by a high-fat diet (HFD) or a methionine- and choline-deficient diet (MCD), employing a series of loss- and gain-of-function experiments. The results showed that liver ORM levels elevated in fat NAFLD models but decreased in lean NAFLD models. Orm1-deficient mice fed either on HFD or MCD had significantly higher NAFLD activity score with more severe steatosis and ballooning, showing an aggravated NAFLD progression. However, liver-specific Orm1 overexpression in mice could not alleviate NAFLD when fed on HFD or MCD. These results suggest that systemic endogenous ORM1 is indispensable in protecting against the development of NAFLD; however, it may not serve as an effective localized therapeutic target for managing the disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Diffuse liver disease is a substantial world-wide problem. With the combination of conventional ultrasound of the abdomen, fat quantification and elastography, appropriate staging of the patient can be assessed. This information allows for the diagnosis of steatosis and detection of fibrosis as well as prognosis, surveillance, and prioritization for treatment. With the potential for reversibility with appropriate treatment accurate assessment for the stage of chronic liver disease is critical., Competing Interests: Disclosure R.G. Barr has received a speaker honorarium from Canon Medical systems, Philips Ultrasound, Siemen Healthineers, Mindray, Samsung Ultrasound, Hologic Ultrasound. He has received research grants from Philips Ultrasound, Canon Ultrasound, Canon MRI, Samsung, South Korea, Siemens Healthineers, Germany, Hologic, United States, Mindray and equipment grants from Canon Medical Systems, United States, Philips Ultrasound, and Siemens Healthineers. He receives royalties from Thieme Publishers and Elsevier Publisher. He is on the advisory panels of Bracco Diagnostics and Lantheus., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart., (© 2024 The Author(s). BioFactors published by Wiley Periodicals LLC on behalf of International Union of Biochemistry and Molecular Biology.)