Search Results (9,073)

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model was induced in male wild-type (WT) and endothelial nitric oxide synthase (eNOS)-deficient (eNOSKO) mice by feeding them a high-fat/cholesterol/cholate diet, and they were administered either a vehicle or pemafibrate at 0.17 mg/kg/day for 10 weeks. Although pemafibrate treatment did not change plasma lipid profiles in either WT or eNOSKO mice, pemafibrate reduced plasma AST levels in both WT and eNOSKO mice compared to the levels in the vehicle-treated mice. Histopathological analysis of the liver showed that MASLD was improved in the pemafibrate-treated groups in both WT and eNOSKO mice. Compared to vehicle treatment, pemafibrate treatment significantly reduced the expression levels of hepatic NADPH oxidase subunit genes, M1 macrophages, inflammatory-cytokine-related genes and profibrotic genes in both WT and eNOSKO mice, along with reduction in hepatic oxidative stress assessed by dihydroethidium staining and 4-hydroxynonenal protein levels. Thus, pemafibrate ameliorated MASLD with reduction in oxidative stress and inflammation even in vascular endothelial dysfunction. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD), a recently proposed term to replace non-alcoholic fatty liver disease (NAFLD), emphasizes the critical role of metabolic dysfunction and applies broader diagnostic criteria. Diagnosis of MAFLD requires evidence of hepatic steatosis combined with obesity, type 2 diabetes mellitus, or other metabolic dysregulation conditions, all of which significantly elevate the risk of chronic kidney disease (CKD). This review discusses the pathological mechanisms of lipid accumulation and insulin resistance in MAFLD and CKD, highlighting their mechanistic connections. Specifically, ectopic fat accumulation triggered by metabolic reprogramming, oxidative stress and inflammation induced by energy overload, modified lipids, uremic toxins, and senescence, as well as insulin resistance pathways activated by pro-inflammatory factors and lipotoxic products, collectively exacerbate simultaneous hepatic and renal injury. Moreover, interactions among hyperinsulinemia, the sympathetic nervous system, the renin–angiotensin system (RAS), and altered adipokine and hepatokine profiles further amplify insulin resistance, ectopic lipid deposition, and systemic damage. Finally, the review explores potential therapeutic strategies targeting lipid metabolism, insulin sensitivity, and RAS activity, which offer promise for dual-organ protection and improved outcomes in both hepatic and renal systems. Full article

Background/Objectives: Dietary quality plays a crucial role in maintaining liver function. In this study, we examined sex differences in the association between dietary quality and elevated liver enzyme levels in Korean adults. Methods: This study included a nationwide sample of 15,997 males and 22,300 females in South Korea. Dietary assessment was performed using the Korean Healthy Eating Index (KHEI), an evidence-based dietary quality index that quantitatively reflects adherence to Korean dietary guidelines (range 0–100). Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured, with individuals classified as having elevated AST or ALT levels when values were ≥40 IU/L or ≥35 IU/L, respectively. Logistic regression analysis was performed to examine the association between the KHEI and elevated AST or ALT levels stratified by sex. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined. Results: Among the males, a 10-point increase in the KHEI score was inversely associated with the likelihood of having elevated AST (OR: 0.90; 95% CI: 0.85–0.96) and ALT (OR: 0.96; 95% CI: 0.92–1.00) levels, respectively. Among the females, there was no clear association between the KHEI and elevated AST (OR: 0.98; 95% CI: 0.91–1.05) or ALT (OR: 1.00; 95% CI: 0.95–1.05) levels. Conclusion: Further research is warranted to elucidate the underlying mechanisms of the observed sex-specific associations and guide the development of targeted dietary interventions for liver health in males and females. Full article

Background: Autoimmune liver diseases (ALDs) are a diverse group of chronic inflammatory disorders. Individuals with a history of one autoimmune disease (AD) are at a substantially increased risk of developing additional autoimmune conditions. Polyautoimmunity has increasingly been recognized as a factor associated with a more complex disease course and poorer long-term outcomes. Methods: This retrospective, cross-sectional observational study reviewed medical records of patients diagnosed with ALDs who had been admitted to the gastroenterology clinic. Results: A total of 457 patients with ALDs were included. Polyautoimmunity was present in 194 patients (42.5%), and multiple autoimmune syndrome (MAS) was diagnosed in 26 of these patients (5.7%). Serological comparisons revealed that antinuclear antibody (ANA) positivity was significantly more common in the polyautoimmunity group. Only 22.2% of the patients with polyautoimmunity were ANA-negative, compared with 52.9% in those without. An ROC curve analysis was conducted to assess the predictive value of clinical and laboratory variables for polyautoimmunity. Among all the tested parameters, ANA positivity (>+2) had the strongest predictive value (AUC: 0.724). A disease duration longer than 6.5 years followed, with a moderate discriminative capacity (AUC: 0.677). Additionally, lower albumin levels (<3.0 g/dL) and elevated erythrocyte sedimentation rates (ESRs) (>29.5 mm/h) were significantly associated with polyautoimmunity. Conclusions: In our cohort, 42.5% of patients had at least one additional autoimmune disorder, highlighting the need for a systemic and comprehensive approach to patient care. Simple and accessible markers—such as ANA titers, disease duration, albumin levels, and ESRs—may help to identify patients at greater risk. Full article

Traumatic liver injury remains a significant contributor to trauma-related morbidity and mortality worldwide. In Saudi Arabia, motor vehicle accidents (MVAs) are the predominant mechanism of injury, particularly among young adults. This study aimed to evaluate the clinical characteristics, management strategies, and outcomes of patients with liver trauma over a ten-year period at a tertiary academic level-one trauma center. A retrospective cohort study was conducted from January 2015 to December 2024. All adult patients (aged 18–65 years) who sustained blunt or penetrating liver injuries and underwent a pan-CT trauma survey were included. Demographic data, Injury Severity Scores (ISSs), imaging timelines, management approach, and clinical outcomes were analyzed. Statistical analysis was performed using JASP software with a significance threshold set at p < 0.05. A total of 111 patients were included, with a mean age of 33 ± 12.4 years; 78.1% were male. MVAs were the leading cause of injury (75.7%). Most patients (80.2%) had low-grade liver injuries and received non-operative management (NOM), with a high NOM success rate of 94.5%. The median time to CT was 55 ± 64 min, and the mean time to operative or IR intervention was 159.9 ± 78.8 min. Complications occurred in 32.4% of patients, with ventilator-associated pneumonia (19.8%) being most common. The overall mortality was 6.3%. Multivariate analysis revealed that shorter time to CT significantly reduced mortality risk (OR = 0.5, p < 0.05), while a positive e-FAST result was strongly associated with increased mortality (OR = 3.3, p < 0.05). Higher ISSs correlated with longer monitored unit stays (ρ = 0.3, p = 0.0014). Traumatic liver injuries in this cohort were predominantly low-grade and effectively managed conservatively, with favorable outcomes. However, delays in imaging and operative intervention were observed, underscoring the requirement for streamlined trauma workflows. These findings highlight the requirement for continuous trauma system improvement, including protocol optimization and timely access to imaging and surgical intervention. Full article

Background/Objectives: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, poses a significant global health concern. Primarily affecting regions in the northern hemisphere, such as northwest China, which are vital for animal husbandry, it often results in severe hepatic impairment in the host. However, there remains a dearth of knowledge concerning changes in gene expression profiles during the progression of AE. In this study, we employed transcriptome sequencing (RNA sequencing, RNA-Seq) to detect alterations in gene expression profiles in the liver tissues of mice with AE. Our aims were to understand the transcriptome differences in the liver during E. multilocularis infection and to explore the molecular mechanisms underlying the early progression of this disease. Methods: We established a mouse model of AE by intraperitoneally injecting protoscoleces of E. multilocularis. All the inoculated mice were randomly divided into four groups. Liver tissues were collected at 6, 12, 19, and 25 weeks after inoculation. Paired non-infected mouse-derived liver tissues were used as controls, and transcriptome sequencing was carried out. Results: A total of 629 differentially expressed genes (DEGs) were identified. Among them, 370 genes were upregulated and 259 genes were downregulated. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were significantly associated with immune system modulation, the cell cycle, and the fibrosis process during the pathological changes. Additionally, weighted gene co-expression network analysis (WGCNA) identified several genes, including CCNA2, BIRC5, KIF2C, OTC, TLR2, and NCKAP1L. These hub genes involved in immunoinflammatory processes may be related to E. multilocularis larvae infection. Conclusions: The findings of this research provide a theoretical foundation for a more in-depth understanding of the molecular mechanisms of AE. They offer valuable insights into the molecular mechanisms and potential key factors involved in the pathogenesis of this disease. Full article

Aim: The frontal QRS-T (fQRS-T) angle serves as an electrocardiography indicator that visually represents the disparity between the frontal QRS axis and the T axis. The heterogeneity between cardiac depolarization and repolarization rises with an increase in the fQRS-T angle. Prior research has demonstrated a relationship between the fQRS-T angle and the extent of atherosclerosis, along with the risk of cardiovascular mortality. The non-alcoholic fatty liver disease fibrosis score (NFS) is a non-invasive scoring tool used to quantify the degree of liver fibrosis in individuals with non-alcoholic fatty liver disease (NAFLD). Non-alcoholic fatty liver disease increases the risk of atherosclerotic cardiovascular disease, which can be predicted using the NFS. The objective of this study is to examine the potential correlation between the fQRS-T angle and NFS in patients with stable angina pectoris. Materials and Methods: This cross-sectional study included 177 (48 women) non-alcoholic patients who underwent coronary angiography due to stable angina pectoris. Individual NFS values were calculated using clinical and laboratory data. Patients were categorized into two groups based on a NFS threshold value of 0.67. Following a minimum fasting period of 12 h, biochemical laboratory parameters were acquired using a peripheral venous sample, and electrocardiographic data were recorded. Results: The univariate logistic regression analysis revealed significant associations between hypertension (p = 0.018), coronary artery disease (p = 0.014), neutrophil (p = 0.024), hemoglobin (p = 0.038), and low-density lipoprotein (LDL, p = 0.007) with the NFS. The electrocardiographic variables related to the score included the QRS duration (p = 0.015), Pmax (p = 0.026), QTC interval (p = 0.02), and fQRS-T angle (p < 0.001). In the multivariate logistic regression analysis, NFS was independently associated with LDL (OR: 0.984, 95% CI: 0.970–0.998, p = 0.024) and fQRS-T angle (OR: 3.472, 95% CI: 1.886–6.395, p < 0.001). Conclusions: The FQRS-T angle may exhibit a distinct correlation with NAFLD. Extensive investigations should validate this link, since the fibrosis score can serve as an effective tool for monitoring patients prior to the onset of clinical symptoms associated with liver fibrosis. Full article

Background: Primary sclerosing cholangitis (PSC) accounts for 10–15% of liver transplants but is the leading cause of retransplant. This study evaluates whether PSC patients have different survival and graft outcomes when receiving grafts from donors after brain death (DBD) versus circulatory (DCD) death. Methods: Using the SRTR database (2004–2024), we compared PSC patients receiving DCD vs. DBD grafts. Demographics and outcomes including graft loss, mortality, and retransplant were analyzed using multivariable logistic and Cox regression, along with propensity-matched analysis. Results: Among 5762 PSC patients, 391 (6.8%) received DCD grafts. Patients receiving DCD grafts were older but had lower MELD scores (19 vs. 22; p < 0.001) and were less often functionally dependent (11.3% vs. 24.4%; p < 0.001). Multivariable Cox regression demonstrated that receipt of a DCD graft was independently associated with time to graft loss (HR 1.59; CI 1.10–2.31; p = 0.013. Similarly, DCD graft receipt significantly increased the likelihood of requiring retransplant (HR 3.25; CI: 1.93–5.46; p < 0.001) but did not increase the likelihood of mortality. Propensity matched analysis further supported these finding with significantly higher graft loss with DCD grafts at one and two years and higher retransplant rates at all time points including 5-years (+7.9%, CI 4.4 to 11.4%; p < 0.001). Conclusions: DCD grafts in PSC patients are linked to worse graft survival and higher retransplant rates. They may be best suited for older, lower-MELD patients, but further studies on perfusion strategies are needed. Full article

Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA CTC-537E7.3 as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with CTC-537E7.3 expression lost in 95% of cases (*** p < 0.0001). It demonstrated excellent diagnostic performance in discriminating tumor from non-tumor tissue (AUC = 0.95), which was maintained in early-stage (I/II) disease. Low CTC-537E7.3 expression correlated with shorter overall and disease-free survival and was inversely associated with serum α-fetoprotein (AFP) levels, highlighting its complementary clinical value. Mechanistic investigation revealed a potential competing endogenous RNA (ceRNA) axis. The microRNA miR-190b-5p was highly expressed in tumors and predicted to bind CTC-537E7.3, while its target, PLGLB1, was significantly suppressed. Survival analysis confirmed that concurrent high expression of CTC-537E7.3 and PLGLB1 conferred superior outcomes. These findings establish CTC-537E7.3 as a liver-specific, ceRNA-mediated tumor suppressor with robust diagnostic and prognostic potential. It represents a promising adjunct to existing HCC surveillance strategies, such as ultrasound and AFP measurement, for high-risk populations. Full article

Background and Objectives: Patients with GG rs738409 patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype (148M variant) have greater risk to develop end-stage liver disease and its associated clinical complications, including hepatocellular carcinoma (HCC). We aimed to analyze the association between the PNPLA3 genotype and augmented inflammatory response in transplant candidates with end-stage alcoholic liver disease (ALD). Materials and Methods: Concentrations of 13 cytokines were measured in 106 end-stage ALD patients without HCC (40 with CC, 40 with CG, and 26 with GG genotype), 35 end-stage ALD patients with HCC, and 19 control patients by cytometric bead array. Results: We found significantly higher concentrations of IL-1, IFN-α, IFN-γ, TNF-α, IL-6, CXCL8, IL-10, IL-12, IL-32, and IL-33 in patients with ALD compared to controls, while the concentration of CCL2 was significantly lower. No differences were observed in the concentration of IL-17 and IL-18. ALD patients with and without HCC had similar cytokine concentrations (p > 0.05 for all comparisons). End-stage ALD patients without HCC of the GG genotype had significantly higher CCL2 concentrations (212.6 [135.9–264.9] pg/mL) compared to end-stage ALD patients without HCC carrying the CC/CG genotypes (141.3 [104.1–201.6] pg/mL, p = 0.002, Mann–Whitney). No significant differences across the genotypes were found for the remaining measured cytokines (p > 0.05). GG carriers also had significantly higher levels of AST and ALT, and lower platelet counts. Conclusions: End-stage ALD patients without HCC who carry the PNPLA3 GG genotype have relatively higher CCL2 levels compared to those with the CC or CG genotypes. Relatively elevated CCL2 concentrations in GG patients might contribute to their increased risk of developing clinical complications compared to CC/CG patients. Full article

Background: Alcohol-associated liver disease (ALD) is characterized by gut–liver axis dysfunction and metabolic dysregulation, yet the therapeutic potential of probiotics remains underexplored. This study aimed to investigate the protective effects and mechanisms of Lacticaseibacillus paracasei 36 (LP36) against ethanol-induced ALD in mice. Methods: Mice were pretreated with LP36 prior to ethanol exposure. Liver injury was assessed through serum ALT/AST levels, hepatic steatosis (TC/TG content), and ethanol detoxification capacity (ADH/ALDH activity). Intestinal barrier integrity was evaluated via Mucin2 and ZO-1 expression, and gut microbiota alterations were analyzed by 16S rRNA sequencing. Hepatic transcriptomics (RNA-seq) was performed to identify key regulatory pathways. Results: LP36 significantly attenuated ethanol-induced liver injury, evidenced by reduced ALT/AST, improved hepatic steatosis (lower TC/TG), and enhanced ADH/ALDH activity. Mechanistically, LP36 restored intestinal barrier function (upregulated Mucin2 and ZO-1), modulated gut microbiota (suppressed Parasutterella, Romboutsia, and Christensenellaceae_R-7_group; enriched Faecalibaculum and Tuzzerella), and reduced systemic inflammation. Transcriptomics revealed LP36-mediated rescue of AMPK signaling, involving regulation of Stk11, Prkag3, lipid synthesis genes (Fasn, Acaca), and metabolic modulators (Creb3l3, G6pc3, mTOR, Rps6kb2).Conclusions: LP36 ameliorates ethanol-induced ALD by enhancing intestinal barrier integrity, reshaping gut microbiota, and restoring AMPK-dependent metabolic homeostasis. These findings highlight LP36 as a promising probiotic candidate for ALD prevention. Full article

Background: Huang Qin Decoction (HQD) is a well-established Traditional Chinese Medicine (TCM) formulation recognized for its application in the treatment of colorectal cancer (CRC). However, the precise therapeutic mechanisms remain inadequately defined. Methods: This study integrates metabolomics from a mouse model and network pharmacology to screen potential targets and bio-active ingredients of HQD. The pharmacological activity of HQD for CRC was evidenced via single-cell RNA sequencing (scRNA-seq), molecular docking, and molecular dynamics simulations. Atomic force microscopy (AFM) assays and cellular experimental validation were used to confirm the relative mechanisms. Results: The metabolite profile undergoes significant alterations, with metabolic reprogramming evident during the malignant progression of CRC liver metastasis. Network pharmacology analysis identified that HQD regulates several metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism, nitrogen metabolism, phenylalanine metabolism, and linoleic acid metabolism, by targeting key proteins such as aspartate aminotransferase (GOT1), cytochrome P450 1A2 (CYP1A2), and carbonic anhydrase 2 (CA2). ScRNA-seq analysis indicated that HQD may enhance the functionality of cytotoxic T cells, thereby reversing the immunosuppressive microenvironment. Virtual verification revealed a strong binding affinity between the identified hub targets and active constituents of HQD, a finding subsequently corroborated by AFM assays. Cellular experiments confirmed that naringenin treatment inhibits the proliferation, migration, and invasion of CRC cells by downregulating GOT1 expression and disrupting glutamine metabolism. Conclusions: Computational prediction and in vitro validation reveal the active ingredients, potential targets, and molecular mechanisms of HQD against CRC liver metastasis, thereby providing a scientific foundation for the application of TCM in CRC treatment. Full article

Prompt and accurate identification of liver metastases from neuroendocrine tumors, arising from the gastrointestinal system and from the pancreas, through the means of both anatomical and functional diagnostic imaging techniques is mandatory. A patient’s prognosis and treatment planning are dependent on these diagnostic procedures. The aim of this narrative review is to depict the common appearance of liver metastases, as well as to depict atypical imaging patterns. Moreover, this review will cover the differential diagnosis between liver metastases from neuroendocrine tumors and other primary and secondary malignant liver lesions, as well as benign liver lesions. Full article

The early detection of liver cirrhosis (LC) is crucial due to its high morbidity and mortality in advanced stages. Reliable, non-invasive diagnostic tools are essential for timely intervention. Exhaled human breath, reflecting metabolic changes, offers significant potential for disease diagnosis. This paper focuses on the emerging role of sensor array-based volatile organic compounds (VOCs) analysis of exhaled breath, particularly using electronic nose (e-nose) technology to differentiate LC patients from healthy controls (HCs). This study included 55 participants: 27 LC patients and 28 HCs. Sensor’s measurement data were analyzed using machine learning techniques, such as principal component analysis (PCA), discriminant function analysis (DFA), and support vector machines (SVMs) that were utilized to uncover meaningful patterns and facilitate accurate classification of sensor-derived information. The diagnostic accuracy was thoroughly assessed through receiver operating characteristic (ROC) curve analysis, with specific emphasis on assessing sensitivity and specificity metrics. The e-nose effectively distinguished LC from HC, with PCA explaining 92.50% variance and SVMs achieving 100% classification accuracy. This study demonstrates the significant potential of e-nose technology towards VOCs analysis in exhaled breath, as a valuable tool for LC diagnosis. It also explores feature extraction methods and suitable algorithms for effectively distinguishing between LC patients and controls. This research provides a foundation for advancing breath-based diagnostic technologies for early detection and monitoring of liver cirrhosis. Full article

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment.  Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials. Full article