Search Results (182)

Background/Objectives: Fat and inflammation confound current magnetic resonance imaging (MRI) methods for assessing fibrosis in liver disease. Sodium or amide proton transfer-weighted MRI methods may be more specific for assessing liver fibrosis. The purpose of this study was to determine the feasibility of sodium and amide proton transfer-weighted MRI in individuals with liver disease and to determine if either method correlated with clinical markers of fibrosis. Methods: T₁ and T₂ relaxation maps, proton density fat fraction maps, liver shear stiffness maps, amide proton transfer-weighted (APTw) images, and sodium images were acquired at 3T. Image data were extracted from regions of interest placed in the liver. ANOVA tests were run with disease status, age, and body mass index as independent factors; significance was set to p < 0.05. Post-hoc t-tests were run when the ANOVA showed significance. Results: A total of 36 participants were enrolled, 34 of whom were included in the final APTw analysis and 24 in the sodium analysis. Estimated liver tissue sodium concentration differentiated participants with liver disease from those without, whereas amide proton transfer-weighted MRI did not. Estimated liver tissue sodium concentration negatively correlated with the Fibrosis-4 score, but amide proton transfer-weighted MRI did not correlate with any clinical marker of disease. Conclusions: Amide proton-weighted imaging was not different between groups. Estimated liver tissue sodium concentrations did differ between groups but did not provide additional information over conventional methods. Full article

Objectives: This study aimed to evaluate the effect of nutritional education on nutritional knowledge, nutritional status, and quality of life in patients with liver cirrhosis. Methods: Thirty patients participated. At baseline, assessments were conducted to collect data on demographics, physical activity, anthropometric and biochemical measures, dietary habits, 24 h food intake, nutritional status, quality of life, and nutritional knowledge. Participants received a 30 min face-to-face nutritional education session by a registered dietitian, repeated after one month. A follow-up phone call was conducted one month later to reinforce the education. Final evaluations were completed one month after the call. Results: A significant upward trend was detected in nutritional knowledge scores after the intervention period (from 7.4 ± 2.76 to 9.2 ± 3.45). The physical component of quality of life improved, while the mental component showed a slight decline. Dietary changes included reduced energy and protein intake among females and increased protein intake in males. In both genders, fat intake increased and carbohydrate intake decreased. Biochemical improvements were observed, including significant reductions in gamma-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and triglycerides in females and alanine aminotransferase and gamma-glutamyl transferase in males. Conclusions: Structured nutritional education may improve nutritional knowledge, dietary behavior, and biochemical markers in cirrhosis patients. Longer follow-up durations may further enhance these improvements. Full article

(1) Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by liver damage similar to alcoholic fatty liver disease, including triglyceride infiltration of hepatocytes, regardless of alcohol consumption. It leads to progressive liver damage, such as loss of liver function, cirrhosis, and liver cancer, and the response rate of drugs under clinical research is less than 50%. There is an urgent need for biomarkers to evaluate the efficacy of these drugs. (2) Methods: MASLD was induced in mice using a High-Fat diet (HF), Western diet (WD), and Methionine/Choline-Deficient diet (MCD) for 20 weeks (4 weeks for MCD). Liver tissue biopsies were performed, and the treatment effects of saponin and non-saponin feeds were evaluated. Fat accumulation and hepatic inflammation were measured, and mRNA sequencing analysis was conducted. The therapeutic effects were validated using patient-derived liver organoids. (3) Results: The NAFLD Activity Score (NAS) significantly increased in all MASLD models compared with controls. Saponin treatment decreased NAS in the HF and WD groups but not in the MCD group. RNA sequencing and PCA analysis showed that the HF saponin response samples were similar to normal controls. DAVID analysis revealed significant changes in lipid, triglyceride, and fatty acid metabolic processes. qRT-PCR confirmed decreased fibrosis markers in the HF saponin response group, and GSEA analysis showed reduced HAMP1 gene expression. (4) Conclusions: Among the diets, red ginseng was most effective in the HF diet, with significant effects in the saponin-treated group. The therapeutic efficacy was better when HAMP1 expression was increased. Therefore, we propose HAMP1 as a potential exploratory biomarker to assess the saponin response in a preclinical setting. In addition, the reduction of inflammation and hepatic iron accumulation suggests that saponins may exert antioxidant effects through modulation of oxidative stress. Full article

Ketosis and fatty liver syndrome are metabolic disorders apparent in dairy cows during the transition period. The study focused on examining how varying levels of milk production in dairy cows might reflect or influence specific blood biochemical markers and liver health as assessed through ultrasonography. A total of 65 Holstein-Friesian cows from six farms were evaluated at three time points as follows: 7 days before expected calving and at 7 and 21 ± 3 days postpartum. Each evaluation included the body condition score (BCS), blood sampling for biochemical analysis, and liver ultrasonography. Based on average farm milk yield, cows were divided into three production groups as follows: GR1 (38.4 ± 6.45 L/day, n = 23), GR2 (42.9 ± 2.77 L/day, n = 24), and GR3 (45.69 ± 7.49 L/day, n = 18). Parameters assessed included liver lipid content and ultrasonographic measurements such as portal vein diameter and depth, liver depth, and liver angle. Significant time-dependent changes were observed in liver size, fat metabolism, and electrolyte balance, especially postpartum. However, no significant differences emerged among the production groups, indicating that these changes likely represent physiological adaptations to lactation. These findings support the use of blood analysis and ultrasonography as practical, minimally invasive tools for routine metabolic health monitoring in dairy cows during the transition period. Full article

Background. Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of the world population. Progression to its inflammatory state, MASH, is associated with increasing liver fibrosis, leading to end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC). SW033291, an inhibitor of 15-PGDH (the PGE2 degradation enzyme), has been shown to increase in vivo regeneration of liver parenchyma, ameliorating oxidative stress and inflammation. We hypothesized that SW033291 abrogates MASH progression by inducing a paucity of the initial apoptotic switch and restoring physiological collagen’s microenvironment. Methods. The expression levels of the cell metabolic proteins FOXO1, mTOR, and SIRT7 were determined in a diet-induced MASH-mouse model at 16, 20, and 24 weeks. Non-targeted metabolomics in mouse plasma were measured by LC-MS/MS. Liver morphology and apoptotic activity were quantified by the NAS score and TUNEL assay, respectively. Statistical analyses between groups (NMC, HFD, and SW033291) were determined by ANOVA, t-test/Tukey’s post hoc test using GraphPad Prism. Metabolomics data were analyzed using R-lab. Results. The treated group showed significant decreases in total body fat, cellular oxidative stress, and inflammation and an increase in total lean mass with improved insulin resistance and favorable modulation of metabolic protein expressions (p < 0.05). SW033291 significantly decreased GS:SG, citric acid, and corticosterone, NAS scores (9.4 ± 0.2 vs. 6.2 ± 0.1, p < 0.05), liver fibrosis scores (1.3 ± 0.5 vs. 0.25 ± 0.1, p < 0.05), and apoptotic activity (43.9 ± 4.6 vs. 0.38 ± 0.1%, p < 0.05) compared with controls at 24W. Conclusions. The inhibition of 15-PGDH appears to normalize the metabolic and morphological disturbances during MASH progression with a paucity of the initial apoptotic switch, restoring normal collagen architecture. SW033291 warrants further investigation for its translation. Full article

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a leading cause of liver cirrhosis, with its global prevalence rising due to obesity, insulin resistance, and type 2 diabetes mellitus. While bariatric surgery remains effective for weight loss, Glucagon-Like Peptide-1 analogs such as liraglutide are emerging as promising pharmacological treatments. This study aimed to evaluate the effects of a 3-month liraglutide treatment on liver steatosis, subclinical markers, and insulin resistance in non-diabetic, obese patients with MASLD. Twenty-eight obese adults (BMI ≥ 30 kg/m²) were treated with daily subcutaneous liraglutide injections for three months. Liver steatosis was assessed using FibroScan^® (CAP score) and non-invasive indices (Hepatic Steatosis Index—HSI, and NAFLD Liver Fat Score—NLFS). Insulin resistance was measured with conventional markers (HOMA-IR, QUICKI) and triglyceride-based indices (METS-IR, TyG). Liraglutide significantly reduced liver steatosis (CAP score: 305 to 268 dB/m, p < 0.05) and improved HSI, while NLFS remained unchanged. Despite significant weight loss, traditional insulin resistance markers remained unchanged, while METS-IR and TyG improved. Liraglutide therapy improved liver steatosis and triglyceride-based insulin resistance markers in non-diabetic obese patients with MASLD. These findings support the use of liraglutide, highlighting the value of personalized approaches and alternative insulin resistance assessments in MASLD management. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH), characterized by liver inflammation, fibrosis, and fat accumulation, can develop into cirrhosis and liver cancer. Despite its increasing prevalence worldwide, there are few established therapies for advanced MASH. We previously demonstrated that stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) exerted therapeutic effects in a MASH mouse model. The gut–liver axis is thought to be associated with liver disease progression, and soluble Siglec-9 (sSiglec-9), an immunoinhibitory receptor, is a key protein in SHED-CM that induces anti-inflammatory macrophages and has intestinal epithelial protective effects. Therefore, we evaluated sSiglec-9’s role in intestinal barrier protection in MASH mice. Methods: We evaluated sSiglec-9 effects on intestinal barrier function using in vitro Caco-2 cell monolayers injured by TNF-α and IFN-γ. For the MASH mouse model, male C57BL/6J mice were given a Western diet and high-sugar solution orally; to induce liver injury, CCl4 was intraperitoneally administered for 12 weeks. Mice were treated weekly with 10 ng/g sSiglec-9 or vehicle. Intestinal permeability was assessed by blood 4 kDa FITC-dextran concentration, and intestinal transcriptomes and liver histology were analyzed. Results: sSiglec-9 decreased intestinal permeability and liver inflammation in MASH mice. sSiglec-9 and SHED-CM reduced 4 kDa FITC-dextran permeability in injured Caco-2 cells, and sSiglec-9 significantly reduced intestinal permeability and modulated expression of 34 intestinal genes. The NAFLD Activity Score indicated significantly reduced inflammation following sSiglec-9 treatment. Conclusions: sSiglec-9 may protect intestinal barrier function by mitigating mucosal inflammation. sSiglec-9 treatment may represent a novel therapeutic approach for MASH via gut–liver axis modulation. Full article

The identification of causal genomic regions for liver fat accumulation in the context of metabolic dysfunction remains a challenging goal. This study aimed to identify potential endophenotypes for liver fat content and employ them in bivariate linkage searches for pleiotropic genetic regions where targeted association analysis is more likely to reveal significant variants. Multiple metabolic risk and adiposity distribution traits were assessed using the endophenotype ranking value. The top-ranked endophenotypes were then used in a bivariate linkage analysis, paired with liver fat content. Quantitative trait loci (QTLs) identified as significant or suggestive were targeted for measured genotype association analyses. The highest-ranked endophenotypes for liver fat accumulation were insulin resistance (IR), visceral adipose tissue (VAT), and high-density lipoprotein cholesterol (HDL-C). The univariate linkage analysis for liver fat content identified one significant QTL at chromosome 17p13.2 (Logarithm of odds score (LOD) = 2.90, p = 1.29 × 10⁻⁴). The bivariate linkage analysis pairing liver fat with IR and VAT improved the localization of two suggestive QTLs at 13q21.31 (LOD = 2.11, p = 9.03 × 10⁻⁴), and 6q21 (LOD = 2.35, p = 5.07 × 10⁻⁴), respectively. Targeted association analyses within the -1-LOD score regions of these QTLs revealed 17 marginally significant single nucleotide polymorphisms (SNPs) associated with liver fat content or its combination with the selected endophenotypes. The endophenotype-informed linkage analysis successfully identified regions suitable for the targeted association analysis of liver fat content, either alone or in combination with IR or VAT, leading to the discovery of marginally significant variants with potential for future functional studies. Full article

Background: Early-life stress and dietary habits are key determinants of metabolic health. This study investigates the combined effects of maternal separation (MS) and a post-weaning high-fat diet (HFD) on liver morphology in male C57BL/6 mice. Methods: Male mice were subjected to MS during early postnatal life or kept unmanipulated (UM). After weaning, animals were assigned to either a control diet (CD) or an HFD, forming four groups: UM-CD, UM-HFD, MS-CD, and MS-HFD. Liver histology, collagen deposition, and both morphometric and stereological parameters were assessed following 16 weeks of dietary intervention. Results: MS and HFD independently altered liver structure, while the combination of both factors intensified these changes. The MS-HFD group exhibited pronounced steatosis, mixed inflammatory infiltrates, and hepatocellular ballooning, with a significantly higher NAFLD Activity Score (NAS). No significant differences were observed in liver fibrosis. Morphometric analysis revealed increased body mass in HFD-fed groups and elevated liver mass in MS-HFD. Liver volume was higher in MS-HFD, though not significantly. Liver stereology revealed reduced numerical density of hepatocytes (Nv_hep) and increased surface density (Sv_hep) in MS groups, with the most pronounced effects in MS-HFD. Conclusions: Maternal separation amplifies the hepatic alterations induced by HFD, promoting early inflammatory and steatotic changes. These findings highlight the significance of early-life stress as a factor increasing susceptibility to diet-induced liver damage. Full article

This study evaluates the effects of a proprietary tannin blend (BX), supplemented with or without sodium monensin (MON), on beef cattle performance, carcass traits, and health. Steers (n = 2986; initial shrunk body weight (SBW) 254 ± 9.2 kg) were allocated into 48 pens (61–62 steers/pen; 12 pens/treatment) fed for 230 d. Treatments included: (1) no feed additives (CTL); (2) BX (7.95 g/animal daily); (3) MON + Tylosin phosphate (TYL; 437.52 mg MON/animal daily + 80 mg TYL/animal daily); or (4) MON + BX (437.52 mg MON/animal daily + 7.95 g BX/animal daily). Data were analyzed in R 4.2.1 using a randomized block design with pen as the experimental unit. Dry matter intake was lower (p < 0.001) in MON + TYL and MON + BX than in CTL. Steers fed MON + BX had greater carcass-adjusted final SBW (p = 0.002), average daily gain (p = 0.002), fat thickness (p = 0.035), and marbling score (p = 0.046) than BX. Feed conversion improved in MON + TYL and MON + BX (p < 0.001). CLT and BX had higher (p < 0.001) liver abscess prevalence compared to MON + BX and MON + TYL. The addition of BX did not improve the parameters measured. Steers fed MON + BX showed reduced liver abscesses and similar feed efficiency compared to MON + TYL. Full article

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally. Probiotic supplementation has shown promise in its prevention and treatment. Although Weissella viridescens, a lactic acid bacterium with immunomodulatory effects, has antibacterial and anti-inflammatory activities, there is a lack of direct evidence for its role in alleviating MASLD. This study aimed to investigate the protective effects of W. viridescens strain Wv2365, isolated from healthy human feces, in a high-fat diet (HFD)-induced rat model of MASLD. Methods: Rats were randomly assigned to a normal chow diet (NC), high-fat diet (HFD), and HFD supplemented with W. viridescens Wv2365 (Wv2365) groups. All groups were fed their respective diets for 8 weeks. During this period, the NC and HFD groups received a daily oral gavage of PBS, while the Wv2365 group received a daily oral gavage of Wv2365. Results: Wv2365 supplementation significantly reduced HFD-induced body weight gain, improved NAFLD activity scores, alleviated hepatic injury, and restored lipid metabolism. A liver transcriptomic analysis revealed the downregulation of inflammation-related pathways, along with decreased serum levels of TNF-α, IL-1β, IL-6, MCP-1, and LPS. Wv2365 also activated the Nrf2/HO-1 antioxidant pathway, enhanced hepatic antioxidant enzyme activities and reduced malondialdehyde levels. A gut microbiota analysis showed the enrichment of beneficial genera, including Butyricicoccus, Akkermansia, and Blautia. Serum metabolomic profiling revealed increased levels of metabolites including indole-3-propionic acid, indoleacrylic acid, and glycolithocholic acid. Conclusions: Wv2365 attenuates hepatic injury, oxidative stress, and inflammation in a rat model of high-fat-diet-induced MASLD, supporting its potential as a probiotic candidate for the modulation of MASLD. Full article

Background: Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) is the accumulation of fat in the liver without excessive alcohol consumption or other known liver diseases. MASLD is the most common liver disease in adolescents with obesity. The aims of this study were as follows: (i) to determine which index (waist circumference BMI, WHtR, VAI, METS-IR, METS-VF, HSI, FLI, or MetS_zscore) best explains the prevalence of MASLD in adolescents with obesity; (ii) to determine whether there was a specific index that was most strongly associated with MASLD; (iii) to assess which liver function indexes were most strongly correlated with MASLD. Methods: A total of 758 adolescents with severe obesity (BMI z-score > 2) admitted at the Division of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo-Verbania for a 3-week multidisciplinary body weight reduction program were selected. Anthropometric parameters (stature, body mass, BMI, and waist and hip circumference) were collected, and body composition (lean and fat mass) was determined using the tetrapolar bioimpedance analysis (BIA) technique. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides (TG), and C-reactive protein (CRP) were measured using standard techniques. MASLD was diagnosed based on abdominal ultrasound results. Results: WHtR (65.76%) was the most sensitive compared with other indexes. The HSI (AUC: 0.67 (0.63–0.71, 95% CI), p-value < 0.05) showed the best performance in predicting MASLD, with the threshold for having MASLD considered at 48.22. The indexes that showed the worst performance in predicting MASLD were the MetS z-score (AUC: 0.56 (0.52–0.60)) and the VAI (AUC: 0.57 (0.52–0.61)). ALT (OR: 2.92 (2.29–3.77); 95% CI) and AST (OR: 2.52 (2.03–3.20)) were the parameters with a stronger correlation with MASLD. Conclusions: The most sensitive index for diagnosing MASLD was the WHtR, based exclusively on anthropometric parameters. HSI was the index that correlated the most with MASLD, while the parameters of liver function (ALT and AST) were the most strongly correlated with the disease and its severity. Full article

This study presents findings from two discrete experimental processes that examined the impact of lameness events on two consecutive, critical time points in the annual production cycle of dairy cattle (early in puerperium—first study, and later at the onset of the reproductive period—second study) regarding liver function, glucose levels, milk production, body condition score, and back fat thickness. In the first study, 47 cows (lame group n = 22, control group n = 25) were monitored from 10 days ante partum (ap) to 46 days post-partum (pp). In the second study, 79 cows (lame group n = 52, control group n = 27) were monitored from day 28 ± 5 pp to day 65–72 ± 5 pp. Lame cows had greater gamma-glutamyl transferase (GGT) concentrations in the blood serum compared to control cows (25.83 vs. 23.56, p = 0.02, respectively) early in puerperium, whereas the two groups did not differ in the second study. The concentration of glutamate dehydrogenase (GLDH) was lower for lame compared to control cows in both studies (17.24 vs. 24.60, respectively, p = 0.02 in the first study, and 30.50 vs. 51.10, respectively, p = 0.02 in the second study). The concentrations of aspartate transaminase (AST) and glucose did not differ between groups in both studies. Lame cows had a lower body condition score (BCS) and backfat thickness (BFT) scores compared to the control in both studies overall. The lame cows of the first study experienced a significant loss of milk production, especially during the second month of lactation, while in the second study, milk production remained unaffected. Conclusively, lame cows have lower BCS and BFT values, whereas milk yield can be negatively affected only if lameness occurs early in the puerperium, probably beginning at the dry period. However, the current research shows that acutely lame cows, as described in this study, exhibit only mild alterations in liver function compared to non-lame ones. Full article

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. Full article

Background: Liver ultrasound segmentation is challenging due to low image quality and variability. While deep learning (DL) models have been widely applied for medical segmentation, generic pre-configured models may not meet the specific requirements for targeted areas in liver ultrasound. Quantitative ultrasound (QUS) is emerging as a promising tool for liver fat measurement; however, accurately segmenting regions of interest within liver ultrasound images remains a challenge. Methods: We introduce a generalizable framework using an adaptive evolutionary genetic algorithm to optimize deep learning models, specifically U-Net, for focused liver segmentation. The algorithm simultaneously adjusts the depth (number of layers) and width (neurons per layer) of the network, dropout, and skip connections. Various architecture configurations are evaluated based on segmentation performance to find the optimal model for liver ultrasound images. Results: The model with a depth of 4 and filter sizes of [16, 64, 128, 256] achieved the highest mean adjusted Dice score of 0.921, outperforming the other configurations, using three-fold cross-validation with early stoppage. Conclusions: Adaptive evolutionary optimization enhances the deep learning architecture for liver ultrasound segmentation. Future work may extend this optimization to other imaging modalities and deep learning architectures. Full article