Search Results (556)

Background/Objectives: Lean metabolic dysfunction-associated steatotic liver disease (lean MASLD) is an increasingly recognized phenotype occurring in individuals with normal body mass index (BMI), despite clinically important hepatic and cardiometabolic risk. This narrative review summarizes current evidence on its epidemiology, pathophysiology, diagnostic challenges, clinical outcomes, and management. Methods: A narrative literature review was conducted using PubMed, Embase, and Cochrane Library from database inception to March 2026. Relevant studies on lean MASLD/lean NAFLD, including cohort studies, meta-analyses, clinical trials, consensus statements, and practice guidelines, were prioritized. Results: Lean MASLD reflects interactions between visceral adiposity, insulin resistance, genetic susceptibility, sarcopenia, dietary and lifestyle factors, vitamin D deficiency, and gut microbiome alterations. Diagnosis is challenging because BMI and aminotransferase levels may underestimate metabolic vulnerability, MASH, or clinically significant fibrosis. Available data suggest increased liver-related events, liver-related mortality, and all-cause mortality compared with individuals without steatotic liver disease, although comparisons with non-lean MASLD remain heterogeneous. Resmetirom and semaglutide have expanded treatment options for noncirrhotic MASH with moderate to advanced fibrosis, but lean patients are underrepresented in pivotal trials. Conclusions: Lean MASLD is an underrecognized but clinically important phenotype. Earlier recognition, fibrosis risk stratification, sarcopenia assessment, cardiometabolic optimization, and lean-specific therapeutic research are needed to improve outcomes. Full article

This study evaluated the impact of lactic acid fermentation on microbiological and nutritional quality, bioactive compound profile, and bioactive properties of mashed navy beans (MNB). Lactic Acid Bacteria (LAB) viability and microbiological quality of fermented mashed navy beans (FMNBs) were maintained for up to 28 days at 4 °C. Fermentation improved protein quality while reducing trypsin inhibitor activity. Additionally, fermentation enhanced the extractability of phenolic compounds, especially of bound forms. Proteolytic activity during fermentation generated low-molecular-weight peptides enriched in hydrophobic residues. Although antioxidant capacity remained comparable between samples, fermented samples exhibited higher angiotensin-converting enzyme inhibitory (ACE-I) activity (IC₅₀ ACE-I = 0.635 ± 0.043 and 0.413 ± 0.002 mg solids mL⁻¹ for MNBs and FMNBs, respectively). Simulated gastrointestinal digestion enhanced both antioxidant (ABTS•+) and antihypertensive potential. ECA-I inhibition was higher in the fermented sample dialysates (D), with IC₅₀ values of 0.160 ± 0.005 and 0.117 ± 0.003 mg solids mL⁻¹ for MNB-D and FMNB-D, respectively, due to the increased dialyzability of phenolic compounds and the presence of hydrophobic low-molecular-weight peptides in FMNB-D. Furthermore, FMNB-D exhibited competitive ACE-I inhibition. These findings demonstrate that lactic fermentation is an effective strategy to enhance the nutritional and health-promoting properties of legume-based foods. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are increasingly recognized as key drivers of hepatocellular carcinoma (HCC). Unlike HCC caused by viral infections or alcohol, MASLD/MASH-related liver cancer develops within a chronic immunometabolic environment characterized by lipotoxicity, sterile inflammation, fibrogenesis, and remodeling of the microenvironment. In this setting, interleukin-10 (IL-10) has attracted growing attention due to its complex, context-dependent roles in immune regulation and tumor immune tolerance. This review explores IL-10 biology and its connection to MASLD/MASH-associated HCC, emphasizing the paradox that IL-10 may diminish harmful inflammation in early stages while promoting immunosuppressive conditions in advanced disease. To supplement existing research, we performed an exploratory reanalysis of publicly available bulk liver RNA-seq data from a mouse model that progresses from MASLD/MASH to HCC. The reanalysis revealed a receptor- and effector-specific rewiring of the IL-10 pathway: while the expression of canonical signaling genes (Stat3, Jak1, Jak2, Tyk2, Socs3) showed minimal changes across stages, receptor subunits (Il10ra, Il10rb) and IL-10-responsive effectors (such as Scd2, related to lipid metabolism, and Ddit4, involved in mTOR and glycolysis regulation) displayed strong stage-dependent induction. This was accompanied by a decrease in hepatocyte signature profiles and an increase in stromal and immune signatures. These results generate new hypotheses and raise key questions—particularly whether a large portion of IL-10 modulation originates from peripheral or non-parenchymal sources, and whether the transcriptional patterns observed reflect protein-level changes—that will require stage-specific, cell-focused human studies incorporating proteomic and cytokine measurements. Full article

The brewing industry remains at the forefront of technological innovation, with growing interest in alternative yeasts. Saccharomyces cerevisiae var. boulardii, a well-established probiotic yeast, has attracted attention for its potential to produce probiotic-enriched beers, offering an option for moderate consumers seeking functional beverages. This mini-review brings together current research on the use of S. boulardii in craft brewing, focusing on fermentation performance, flavour and sensory characteristics, and potential health-related functions. While often regarded as a variant of S. cerevisiae, S. boulardii shows comparable or greater cell growth, increased acetic acid production at the expense of glycerol, and lower alcohol yield compared to S. cerevisiae. Despite these differences, beers brewed with S. boulardii exhibit similar volatile compound profiles and sensory characteristics to those produced with S. cerevisiae. In terms of health-related attributes, S. boulardii-fermented beers show higher antioxidant activity, the presence of malto-oligosaccharides with prebiotic potential, and the ability of yeast to survive both storage and gastrointestinal transit. Strategies explored to optimise its brewing performance and customer acceptance include co-fermentation with S. cerevisiae, modified mashing protocols, and natural flavour additions. Overall, the available evidence supports S. boulardii as a promising yeast for developing probiotic-enriched beers. Further research is needed to validate current findings at commercial scales, investigate host–microbiome interactions following beer consumption and develop strategies that balance probiotic efficacy and desirable beer appearance over shelf life. The paper may assist brewers in making informed decisions about deploying S. boulardii, aligning consumer interest in functional beverages with the enjoyment of beer. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread pathology requiring adequate preclinical models for studying pathogenesis and evaluating therapeutic and preventive agents. This study compared differential markers of MASLD pathogenesis in rats using two distinct dietary models: a choline-deficient high-fat diet (HFD-CD) and a cholesterol-enriched high-fat diet (HFD+CHOL). Male Wistar rats were fed either a control AIN93M diet, HFD-CD (40% fat, 20% fructose, and choline deficiency), or HFD+CHOL (40% fat, 20% fructose, and 1% cholesterol) for 56 days. Comprehensive assessment included phenotypic, biochemical, hematological, histomorphological parameters, oxidative stress markers, hepatocyte apoptosis, cytokine levels, and hepatic gene expression. HFD-CD induced steatosis with moderate insulin resistance, increased malondialdehyde levels, and suppressed Acaca, Scd and ChREBP gene expression. In contrast, HFD+CHOL caused macrovesicular steatosis, inflammation, early fibrosis, atherogenic dyslipidemia, intrahepatic cholesterol accumulation, hepatocyte apoptosis, upregulated Srebf1, Cyp7a1, and Nfkb1 expression, and activated Nrf2-dependent antioxidant responses. HFD-CD and HFD+CHOL induce two pathogenetically distinct MASLD phenotypes. The HFD-CD model, characterized by steatosis and oxidative stress without pronounced inflammation or fibrosis, is preferable for studying the preventive potential of bioactive food compounds. Conversely, the HFD+CHOL model with inflammatory and fibrotic components is more suitable for evaluating therapeutic agents aimed at mitigating inflammation, restoring cholesterol homeostasis, and attenuating fibrosis. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasingly prevalent global health concern driven by metabolic imbalance and excess caloric intake, leading to hepatic steatosis, inflammation, and fibrosis that may progress to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, or hepatocellular carcinoma. Current management relies primarily on lifestyle interventions and, in advanced stages, pharmacological therapies; however, long-term outcomes remain limited due to variable efficacy and poor sustainability. Recent advances in pharmacotherapy, including GLP-1 receptor agonists, THR-β agonists and SGLT2 inhibitors, have shown clinically meaningful improvements in metabolic parameters and hepatic steatosis, although their impact on fibrosis and long-term disease modification remains uncertain. In parallel, genomic and nanotechnology-based strategies (such as RNA-based therapies and nanoparticle delivery systems) have emerged as promising approaches to enhance drug stability, targeting, and therapeutic precision. Despite these advances, most emerging strategies remain at preclinical or early translational stages, with significant challenges related to safety, scalability, regulatory approval, and long-term efficacy. In this context, this review provides an integrative synthesis of pharmacological, genomic, and nanotechnology-based therapies, highlighting their mechanisms, limitations, and translational potential. Future research should focus on well-designed clinical trials, standardized evaluation frameworks, and the development of personalized therapeutic approaches. The convergence of these strategies may enable more effective and durable interventions for MASLD. Full article

The recent redefinition of steatotic liver diseases, introducing metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), reflects a growing consensus among liver societies and marks a paradigm shift in disease classification. MASLD subsumes former categories of nonalcoholic fatty liver disease (NAFLD) and incorporates metabolic criteria alongside moderate alcohol intake, while MASH replaces nonalcoholic steatohepatitis (NASH), aligning terminology with disease mechanisms. This evolution clarifies the diagnostic criteria and minimizes stigma, facilitating more consistent epidemiological and clinical investigations. Recent advances in noninvasive diagnostics, including vibration-controlled transient elastography, magnetic resonance elastography, shear-wave elastography, and the Enhanced Liver Fibrosis test, have improved the identification and stratification of patients with advanced fibrosis. Current guidelines recommend targeted screening in populations at elevated metabolic risk, enabling earlier intervention and personalized management. Population studies indicate that MASLD affects over one-third of adults and is a major contributor to cardiovascular and metabolic morbidity. Therapeutic progress is highlighted by the approval of novel agents such as resmetirom and semaglutide for the treatment of MASH with fibrosis. Emerging dual and triple agonists, as well as sodium–glucose cotransporter inhibitors, offer additional promise, although further research is required to define their long-term efficacy and safety. As the disease prevalence escalates globally, the integration of multidisciplinary care, the ongoing refinement of diagnostic tools, and the expansion of therapeutic options will remain essential to optimizing outcomes for affected individuals. Full article

Background: Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of MASLD; however, large-scale clinical data characterizing prevalence patterns, phenotypic subtypes, and disease-specific associations remain limited. Methods: This cross-sectional study enrolled 2549 MASLD patients with gastrointestinal symptoms undergoing lactulose methane–hydrogen breath testing and transient elastography. Univariate and multivariable analysis identified independent risk factors for SIBO. We also explore the distribution of SIBO subtypes and their associations with comorbidity profiles across the MASLD spectrum. Results: The overall prevalence of SIBO was 66.3%, escalating from 65.9% in MASL to 72.8% in at-risk MASH and 78.9% in cirrhosis, alongside a notable enrichment of the intestinal methanogen overgrowth (IMO) phenotype. Multivariable analysis identified advanced fibrosis (stage F4; OR = 1.75, 95% CI: 1.03–2.96), gastroesophageal reflux disease (GERD; OR = 1.66, 95% CI: 1.22–2.28), and coronary artery disease (CAD; OR = 1.80, 95% CI: 1.06–3.06) as independent predictors of SIBO. Additionally, elevated ALT (OR = 1.01, 95% CI: 1.01–1.13) showed a modest association with SIBO. Subtype analysis revealed that IMO was associated with GERD, alcohol consumption, CAD, and obesity, while a history of cholecystectomy and elevated triglycerides were linked to early-phase hydrogen peaks. Conclusions: SIBO is highly prevalent among patients with MASLD, with its prevalence and phenotypic subtype distribution being closely associated with disease severity. The identification of fibrosis-specific risk factors and subtype–clinical associations suggest consideration of SIBO assessment in advanced MASLD, particularly in patients with cardiometabolic or gastrointestinal comorbidities. Full article

Background/Objectives: It is estimated that one in three adults in the US has one or more risk factors for cardiovascular–kidney–metabolic (CKM) syndrome. The American Heart Association (AHA) has warned that the interaction between obesity, Type 2 diabetes (T2D), chronic kidney disease (CKD), and cardiovascular disease (CVD) leads to a multistage CKM syndrome with elevated mortality. This narrative review describes the newly coined terms CKM health and CKM syndrome, introduced by the AHA Presidential Advisory in 2023. Methods: In this narrative review, we will discuss the epidemiology and development of CKM syndrome, CKM stages, and the possible impact of precision nutrition on CKM and evaluate what is currently known about the role of nutrient metabolism in the physiological state and pathogenesis of CKM. Results: Since the AHA defined CKM syndrome in 2023, several studies have analyzed NHANES data to identify the correlations between CKM stages and adverse health outcomes. Studies also found that correlations between dietary intake and diet patterns may contribute to the protection against progression through various stages of CKM. However, experimental research and clinical studies are still lagging. Although the liver plays an integral role in nutrient metabolism, energy homeostasis, protein synthesis, nutrient storage, antibody production, and detoxifying compounds, it has not been included in the definition of CKM. Conclusions: Integrated body systems contribute to the development and progression of CKM. Precision nutrition and dietary patterns may play a role in the management of CKM and related comorbidities. Further research is warranted to address the role of precision nutrition in the prevention, early detection, and intervention in CKM syndrome as part of a comprehensive approach. It would be worth considering including metabolic dysfunction-associated liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) within the CKM framework. Full article

Background/Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by severe hepatic steatosis, lobular inflammation, and fibrosis. Although hesperidin, a citrus-derived flavanone, has been reported to exert metabolic and anti-inflammatory effects, its role in severe inflammatory and fibrotic conditions such as MASH remains incompletely understood. This study aimed to evaluate the effects of hesperidin in MASH using integrated in silico and in vivo approaches. Methods: Potential targets of hesperidin were identified using network pharmacology and molecular docking. For in vivo validation, C57BL/6 mice were fed a methionine- and choline-deficient (MCD) diet for five weeks, with oral administration of hesperidin (150 or 300 mg/kg/day) starting from week two. The MCD model induces severe hepatic inflammation and fibrosis but does not fully reflect metabolic features such as obesity and insulin resistance. Hepatic histology, serum transaminases, immune cell populations, and hypothalamic neuroinflammatory markers were assessed. Results: In silico analyses suggested that hesperidin interacts with key regulators associated with MASH, including PPARG, TGFB1, and TNF. In the in vivo MCD-induced model, hesperidin treatment reduced hepatic lipid accumulation and collagen deposition, accompanied by significant decreases in serum ALT and AST levels (by approximately 30–34% and 42–53%, respectively, depending on dose). These effects were associated with downregulation of pro-inflammatory and pro-fibrogenic gene expression and increased expression of antioxidant markers. In addition, hesperidin decreased circulating Ly6C^high monocytes and hepatic Kupffer cells, along with reduced hypothalamic microglial and astrocyte activation. Conclusions: Hesperidin attenuated key pathological features of MASH, including steatosis, inflammation, and fibrosis, and was associated with modulation of peripheral immune responses and central neuroinflammatory markers. These findings suggest that hesperidin may influence the liver–immune–brain axis and warrant further investigation in models that more closely reflect human metabolic conditions. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive stage of metabolic dysfunction-associated steatotic liver disease characterized by lipid dysregulation, oxidative stress, inflammation, and fibrosis. Because these processes occur simultaneously, compounds targeting multiple pathways may offer therapeutic benefit. Naringin, a citrus-derived flavonoid, has reported antioxidant and anti-inflammatory properties, but its integrated effects in MASH remain unclear. In this study, the effects of naringin were evaluated using combined in silico analysis and in vivo experiments. Network pharmacology and molecular docking predicted targets related to lipid metabolism, oxidative stress, inflammation, and fibrosis, which were validated in a methionine- and choline-deficient diet-induced mouse model. Naringin reduced hepatic lipid accumulation and improved serum AST and ALT levels. It modulated oxidative stress-related genes, attenuated inflammatory responses, and reduced fibrogenic markers. Naringin also decreased Ly6Chigh inflammatory monocytes and Kupffer cell activation, and reduced hypothalamic microglial activation. These findings suggest that naringin exerts multi-target effects across hepatic, systemic, and central pathways, supporting its potential as a therapeutic candidate for MASH. Full article

Background/Objectives: Chronic liver diseases, including metabolic dysfunction-associated steatohepatitis (MASH) and chronic viral hepatitis (CVH), are major global health concerns due to their potential progression to cirrhosis, liver failure, and hepatocellular carcinoma. Because liver biopsy, despite meeting the diagnostic gold standard, is invasive and associated with complications, non-invasive fibrosis assessment tools have been increasingly recommended in clinical practice. This study aimed to compare the diagnostic performance of several non-invasive fibrosis markers (ARR, APRI, FI, FIB-4, API, NFS, BARD) and transient elastography in detecting advanced liver fibrosis (F4) in patients with MASH and CVH. Methods: This retrospective study included 237 adult patients (77 MASH, 160 CVH) who underwent liver biopsy between 2017 and 2025 at the University Clinical Center of Serbia. CVH included chronic hepatitis B (CHB) and C (CHC). Patients were evaluated using serum fibrosis indices and TE, and results were compared to histological staging (F0–F4). ROC analysis assessed diagnostic performance. Results: Cirrhosis (F4) was more common in CVH than MASH (p < 0.001). In MASH, NFS (AUROC 0.931), FIB-4 (0.915), BARD (0.872), and APRI (0.878) showed high diagnostic accuracy for F4. In CHC, APRI (0.931), FIB-4 (0.863), and TE (0.938) had strong performance, while in CHB, TE (0.987) outperformed FIB-4 (0.821). Sensitivity and specificity varied by test and cohort, with TE consistently yielding the best results where available. Conclusions: Non-invasive methods, particularly NFS and FIB-4 for MASH and TE for CVH, effectively identify advanced fibrosis. Their application could significantly reduce the need for biopsy, especially in high-risk groups. TE demonstrated superior accuracy, but access limitations highlight the continued relevance of serum-based scores. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide and a major contributor to the global cardiometabolic burden. Early identification of patients at risk of metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis is essential to prevent liver-related and cardiovascular complications. In Spain, the burden of MASLD is increasing, yet information on routine clinical management by gastroenterologists remains limited. Methods: A nationwide cross-sectional online survey was conducted among members of the Spanish Society of Digestive Diseases (SEPD). The questionnaire explored five domains: MASLD knowledge, use of non-invasive biomarkers and imaging, awareness and implementation of clinical guidelines, cardiometabolic and alcohol-related risk assessment, and coordination with primary care. Results: A total of 429 specialists responded, 33.1% reported more than 20 years of practice and most worked in public hospitals, including 29.2% in large tertiary centers. Awareness of the MASLD definition was high, and 91.2% identified fibrosis as the main prognostic determinant. Non-invasive fibrosis biomarkers were widely used, whereas steatosis biomarkers were less frequently applied. Elastography was available to 96.1%. Guideline knowledge was reported by 80.4%, although implementation was lower. Cardiovascular risk evaluation varied: 75.1% reported systematic screening. Alcohol consumption was usually assessed. Coordination with primary care was limited: 91.1% expressed concerns regarding physicians’ familiarity with MASLD classification, and only 31.1% reported shared protocols. Conclusions: Spanish gastroenterologists show high awareness of MASLD and broad access to non-invasive diagnostic tools. However, important gaps remain in cardiovascular and alcohol risk assessment, guideline implementation, and coordination with primary care. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) is a complex, multifactorial disease heavily influenced by the gut–liver axis. While enterotoxigenic Bacteroides fragilis (ETBF) and its principal virulence factor, B. fragilis toxin (BFT)—a zinc-dependent metalloprotease—are well-known for disrupting intestinal barriers, their potential systemic impact on distant organs remains an emerging area of interest. Although various gut-derived factors contribute to hepatic inflammation, the precise molecular triggers that exacerbate the transition from simple steatosis to progressive fibrosis remain incompletely understood. This review proposes the “Direct Structural Disruption” hypothesis, examining the biological activity of BFT and its proposed role in MASH pathogenesis. We postulate that under permissive conditions, systemic BFT may target hepatic structural proteins (e.g., cadherins). This hypothesized architectural impairment amplifies canonical fibrogenic signaling and hepatic stellate cell (HSC) activation. In addition, we discuss current challenges in the detection and characterization of systemic BFT, particularly the technical limitations in clinical diagnostics stemming from its profound structural homology with host metalloproteinases. Future research integrating advanced diagnostic methodologies and liver-specific in vivo models is essential to elucidate these pathophysiological mechanisms and evaluate the ETBF-BFT axis as a complementary target in progressive MASH. Full article

This study investigated whether storage changes the composition of Fontane and Challenger potatoes, including their starch characteristics, and whether these changes impact the properties of (deep-fried) mashes made from these potatoes stored for up to eight months. Fontane mashes showed an increase in firmness and viscoelasticity when potatoes were stored for a longer time. Moreover, when deep-fried mashes were made with Fontane potatoes, more water evaporated during deep frying and the resultant oil content increased as a function of the storage duration of the potatoes used to make them. This was not observed in mashes made from Challenger potatoes. Since the potato composition, starch characteristics and molecular mobility in mashes were minimally impacted by potato storage for both cultivars, it is assumed that storage-induced changes in potato cell walls and/or pectin methyl esterase activity contribute to the observed differences between deep-fried mashes made from fresh versus stored Fontane potatoes. The acquired insights help understand how potato storage can impact the properties of (deep-fried) potato mash-based products and highlight the potential to mitigate storage-induced declines in product quality by selecting cultivars based on the potato storage time. Full article