Search Results (102)

High-starch diets are increasingly used in aquafeeds to reduce feed costs, but carnivorous fish such as largemouth bass (Micropterus salmoides) have limited capacity to utilize dietary starch and are prone to hepatic metabolic disorders. In the present study, we evaluated whether dietary N-carbamylglutamate (NCG) could alleviate high-starch-induced hepatic oxidative stress and liver injury in largemouth bass. Fish were fed a control diet containing 11.50% starch, a high-starch diet containing 18.00% starch, or a high-starch diet supplemented with 0.15%, 0.20%, or 0.25% NCG for 8 weeks. Compared with the high-starch group, dietary NCG supplementation significantly reduced serum glucose and triglyceride levels, decreased hepatic glycogen and malondialdehyde contents, and increased hepatic superoxide dismutase and glutathione peroxidase activities. NCG also reduced serum alanine aminotransferase and aspartate aminotransferase activities and alleviated hepatic histopathological damage. At the transcriptional level, NCG upregulated genes related to insulin signaling, glycolysis, lipid catabolism, and antioxidant regulation, including insr, irs, gk, pk, atgl, hsl, ampk, and nrf2, while downregulating the expression of keap1, nf-κB, mtor, and multiple inflammation- and apoptosis-related genes. These changes were accompanied by increased serum nitric oxide levels and improved survival and growth performance under high-starch feeding conditions. Collectively, these results indicate that dietary NCG supplementation attenuates high-starch-induced hepatic oxidative stress and redox-associated liver injury in largemouth bass, which may be associated with the transcriptional modulation of genes related to the AMPK/Nrf2/Keap1 and mTOR/NF-κB signaling pathways. Full article

Mulibrey nanism is a rare autosomal recessive multisystem disorder caused by biallelic loss of function variants in TRIM37 encoding a peroxisomal E3 ubiquitin ligase. Initially described in Finland, where it remains most prevalent due to a founder mutation, the condition is now recognized worldwide and is characterized by severe prenatal-onset growth failure, distinctive craniofacial features, radiological abnormalities, ocular findings, and hepatopathy. Although its clinical spectrum extends far beyond these core manifestations, the major determinant of morbidity and mortality is progressive cardiovascular disease, including constrictive pericarditis and restrictive cardiomyopathy. Additional features include metabolic dysfunction such as insulin resistance and type 2 diabetes, gonadal insufficiency, skeletal abnormalities including fibrous dysplasia, and an increased risk of benign and malignant tumours. The clinical course evolves across the lifespan from early growth and developmental abnormalities to progressive multisystem disease in adolescence and adulthood. Recent advances have expanded understanding of TRIM37 function, linking it to mTORC1 TFEB signalling autophagy, centrosome integrity, extracellular matrix regulation, and immune cell function, providing mechanistic insights into tumour predisposition, skeletal pathology, and immune dysregulation. Management remains supportive and requires multidisciplinary care with emphasis on early recognition and treatment of cardiac disease, metabolic complications, and malignancy risk. Prognosis is variable but improves with early diagnosis and appropriate surveillance. This review summarises the clinical spectrum molecular mechanisms and current management of Mulibrey nanism and highlights priorities for future research. Full article

Pulmonary hypertension (PH) can be defined as a mean pulmonary artery pressure (mPAP) greater than 20 mm Hg at rest during right heart catheterization (RHC). The reported prevalence of PH throughout the globe has been estimated to impact approximately 1% of the total population, with a majority of those afflicted being women more than men. Numerous etiologies give rise to the pathophysiology of PH, including heart disease (i.e., left-sided heart failure), lung diseases, and other unclear causes related to chronic stages and complications surrounding long-standing pulmonary thromboembolisms, side effects of certain medications, and genetic and environmental factors. Untreated PH can lead to severe morbidities such as cardio-renal syndrome and congestive hepatopathy (cardiac cirrhosis). Management of PH focuses on decreasing pulmonary pressures by using vasodilators such as prostanoids, and phosphodiesterase type 5 (PDE-5) inhibitors, as well as newer treatments such as sotatercept, which inhibits activin signaling, thereby inhibiting excessive cell growth in the pulmonary artery vasculature and down-regulating the pro-proliferative pathways. Full article

Background: Glutaric acidemia type 1 (GA1) is an autosomal recessive neurometabolic disorder caused by pathogenic variants in glutaryl-CoA dehydrogenase (GCDH), with variable clinical severity despite early biochemical detectability. Population-specific mutational spectra and genotype–phenotype correlations remain insufficiently defined in infantile-onset disease. Therefore, this study aimed to define the GCDH variant spectrum in GA1 patients with mild hepatopathy and assess genotype–phenotype correlations. Methods: We performed integrated clinical, biochemical, and molecular characterization of 15 unrelated patients with infantile-onset GA1. Whole-exome sequencing (WES) was performed for all participants, and the resulting data were compared with the reference sequence of the GCDH gene. Results: All patients presented within the first 6 months of life with macrocephaly, seizures, dystonia, and feeding difficulties. Neurological impairment and mild hepatopathy were variably observed, and one patient developed an acute encephalopathic crisis. Six homozygous GCDH variants were identified, predominantly missense. A common variant, c.541G>C (p.Glu181Gln), accounted for 73.3% of cases and defined a consistent phenotype of early macrocephaly and movement disorder with frequent mild hepatic involvement, suggesting regional enrichment and raising the possibility of a founder effect that warrants confirmation in future haplotype studies. A truncating variant, c.382C>T (p.Arg128Ter), was associated with severe early encephalopathy. Exon 6 represented a mutational hotspot. Biochemically, all patients showed elevated urinary glutaric and 3-hydroxyglutaric acids, increased glutarylcarnitine, and low-to-normal free carnitine, with higher metabolite levels in clinically more severe cases. All variants were pathogenic or likely pathogenic and extremely rare in population databases. Conclusions: This cohort reveals a striking predominance of the GCDH c.541G>C variant and establishes a clear biochemical signature with genotype-associated clinical patterns in infantile-onset GA1. These findings support a population-specific mutational spectrum, refine genotype–phenotype correlations, and underscore the importance of early molecular diagnosis to guide targeted neurological and hepatic monitoring as well as regional screening strategies. Full article

Genetic liver diseases encompass a heterogeneous group of conditions that disrupt hepatic development, structure, or function. Advances in high-throughput sequencing have revealed the molecular basis of many disorders previously defined only by clinical or biochemical features, transforming diagnostic and therapeutic approaches. This review proposes a mechanistic framework that distinguishes diseases arising from developmental abnormalities from those caused by functional impairments in hepatocellular or biliary physiology. It outlines how defects in transporters, enzymes, signaling pathways, intracellular trafficking, and mitochondrial function converge to produce diverse hepatic phenotypes. Moreover, translational aspects are discussed such as how the growing integration of genetic testing into clinical practice enables precise diagnosis, informs prognosis and therapy, and refines disease classification. Finally, the review discusses future directions in the field, emphasizing the role of multi-omic approaches, organoid modeling, and data sharing in elucidating unresolved pathogenic mechanisms and advancing precision hepatology. Full article

Introduction: Ubiquinol–cytochrome c reductase core protein II (UQCRC2) encodes a core subunit of the mitochondrial electron transport chain (ETC) complex III (CIII). Biallelic pathogenic variants in UQCRC2 have been associated with mitochondrial disease characterized by lactic acidosis, developmental delay, hepatopathy, and episodic metabolic decompensation. Methods: We reviewed the biochemical phenotypes of 14 individuals possessing UQCRC2 variants, including two novel cases. We performed biochemical studies of mitochondrial respiration and oxidative phosphorylation (OXPHOS) complex measurements in patient-derived fibroblasts. Results: We report reduced CIII activity in a majority of individuals possessing variants in UQCRC2, as well as biochemical findings consistent with impaired mitochondrial energy metabolism, though impairments in mitochondrial respiration were variable. The two previously unreported, unrelated patients possessing the likely pathogenic missense variant c.361T>C, p.Tyr121His in UQCRC2 in trans with a 16p12.2 microdeletion encompassing UQCRC2 showed milder phenotypes, less severe metabolic decompensations, and no long-term neurological impairments. Both individuals display reduced CIII activity and mitochondrial respiratory dysfunction. Discussion: These data expand the current understanding of genotypes associated with UQCRC2-associated mitochondrial disease to include the novel 16p12.2 microdeletion. These data also highlight the consistent biochemical phenotype associated with UQCRC2-associated mitochondrial disease, and the need for consistent biochemical and respiratory assessment of individuals possessing UQCRC2 variants to further our understanding of this phenotype. Full article

Background: Transcatheter edge-to-edge repair (TEER) has emerged as an established treatment option for patients with severe mitral (MR) and tricuspid regurgitation (TR) who are at high surgical risk. Patients referred for TEER frequently present with advanced comorbidities, including cirrhosis or chronic liver disease (CLD). Hepatic dysfunction, driven by chronic venous congestion and impaired cardiac output, represents a key yet underrecognized determinant of prognosis in this population. The impact of TEER on hepatic function and outcomes in patients with advanced liver disease remains incompletely defined. Methods: This systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO. A comprehensive literature search of PubMed, Scopus, Web of Science, and the Cochrane Library was performed up to 16 January 2026, without language restrictions. Studies evaluating mitral or tricuspid TEER in adult patients with cirrhosis, chronic or advanced liver disease, congestive hepatopathy, or cardiohepatic syndrome were included. Hepatic function was assessed using biochemical markers, clinical diagnoses, or composite scores such as Model for End-Stage Liver Disease (MELD) score and Model for End-Stage Liver Disease Excluding INR (MELD-XI). A qualitative synthesis was performed due to heterogeneity in study design and outcome reporting. Results: Twelve studies were included, comprising prospective and retrospective cohorts, registry-based analyses, mechanistic studies, and one illustrative case report. Six studies evaluated mitral TEER (M-TEER) and six tricuspid (T-TEER). Across both valve interventions, impaired baseline hepatic function was consistently associated with increased mortality and adverse clinical outcomes. MELD and MELD-XI scores emerged as robust prognostic markers following both M-TEER and T-TEER. Successful reduction in valvular regurgitation was associated with stabilization or improvement of hepatic parameters in selected patients, particularly after T-TEER. However, advanced cardiohepatic syndrome and limited hepatic reserve were linked to poor outcomes despite procedural success. Conclusions: Hepatic dysfunction is a powerful determinant of prognosis in patients undergoing M-TEER and T-TEER. While TEER may improve hepatic congestion and liver-related parameters in selected patients, outcomes are highly dependent on baseline hepatic reserve and global hemodynamic status. A personalized approach integrating hepatic assessment into patient selection and risk stratification is essential to optimize outcomes in this complex and growing population. Full article

It is known that the composition of the intestinal microbiota (IM) is associated with the pathogenesis of viral hepatitis. Hepatitis C virus (HCV) is an RNA virus that affects about 50 million people worldwide. HCV infection is considered a major risk factor for developing liver cirrhosis and hepatocellular carcinoma. The liver is closely related to bacterial components derived from the bacteria of the IM through the gut–liver axis, influencing host susceptibility to certain diseases, such as the development of hepatopathy associated with HCV infection. This review specifically evaluates the association of HCV infection with the bacterial IM, focusing on key aspects, such as the evolving intestinal dysbiosis during the natural history of the infection and the effect of treatment (antibiotics, direct-acting antivirals, pre/probiotics, and diet) in the management of these patients, in the different stages of the disease, up to HCC. Full article

The fish liver, as the main detoxification organ, is highly susceptible to xenobiotic exposure, often resulting in various hepatopathies. The cytochrome P450 system plays a central role in xenobiotic metabolism, with cytochrome P450 reductase (CYPOR) supplying the electrons required for CYP enzyme activity. This study aimed to evaluate the relationship between the ecological state of a reservoir and fish health, including CYPOR levels, through hematological, bacteriological, and histological analyses. Samples of water and fish were collected from 12 littoral sites of Lake Ladoga. A total of 1360 specimens of fish from carp (Cyprinidae) and perch (Percidae) families were examined. For histological examination and CYPOR level determination, we selected 40 specimens using a blind randomization method. This sample size was sufficient for statistical analyses. Hematological smears were stained with azure eosin; bacteriological cultures were grown on multiple media; liver samples were stained with hematoxylin and eosin and Sudan III. CYPOR levels in liver homogenates were measured by ELISA-test. Physical and hydrochemical analyses indicated a high pollution level in the littoral zones. Isolated bacterial species were non-pathogenic but exhibited broad antibiotic resistance. Hematological evaluation revealed erythrocyte vacuolization and anisocytosis. Histological analysis showed marked fatty degeneration in hepatocytes, indicating toxic damage. CYPOR concentrations ranged from 0.3–0.4 ng/mL in healthy fish to 5–6 ng/mL in exposed specimens, showing strong correlation between environmental influence and enzyme activity. These findings demonstrate the potential of CYPOR as a sensitive biomarker for biomonitoring programs. The integrated methodological approach provides a model for assessing aquatic ecosystem health and identifying zones requiring priority remediation. Full article

Background: Preventing postoperative infections in hand surgery is an important factor for achieving sustainable results of surgical procedures. To prevent infections, especially when implants are used, preoperative prophylactic antibiotics are applied in adherence to predominantly national guidelines, which are not specifically tailored to hand surgery. However, several studies related to elective soft tissue hand surgery indicate that the preoperative use of antibiotics does not reduce the incidence of postoperative infections. Evidence regarding their efficacy in osteosynthesis of the hand and wrist remains limited. Methods: In this retrospective study, we analyzed 542 adult patients who underwent hand or wrist osteosynthesis between 2016 and 2019 at our university center. They were enrolled in an antibiotic treatment group and a control group without antibiotic treatment. The prophylaxis group (P) underwent surgery in the main operating theater under intravenous anesthesia, whereas the non-prophylaxis group (NP) was treated under WALANT (Wide Awake Local Anesthetic No Tourniquet) in an outpatient operating theater without receiving preoperative antibiotics. Theater construction and installation were otherwise similar, and both were classified as grade 1 theaters. We applied propensity modeling and inverse probability of treatment weighting (IPTW) to achieve balanced treatment groups with respect to risk factors for infection, and we calculated the odds ratio of prophylaxis and infection. Inclusion factors for risk of infection were age, female sex, smoking, diabetes, metabolic disease, inflammatory disease, substance abuse, cardiovascular disease, hepatopathy, renal disease, polytrauma, open fracture, being a manual worker, and occupational accidents. To assess the severity of the cases, we considered whether the fractures were intraarticular, multi-fragmentary, or open, and we collected data on the types of surgical implants that were used. Results: No significant association was found between antibiotic prophylaxis and postoperative infection rate (infection rate P: 3.86%; NP: 3.27%; unadjusted OR: 1.19; adjusted OR after IPTW: 1.09). In terms of risk factors, there was an insignificant trend of higher infection rates in the subgroups smoking, cardiovascular disease, open fracture, occupational accident, and open fixations. Conclusions: In this cohort, routine use of preoperative antibiotics in hand osteosynthesis did not reduce infection rates. The effectiveness of the widespread standardized application of prophylactic antibiotics to reduce the risk of postoperative infections in osteosynthesis of the hand and wrist remains debatable. Our findings set the basis for further prospective studies aiming at clearer guidelines for evidence-based perioperative patient care. Full article

Spectral detector computed tomography (SDCT) is an innovative imaging technique in veterinary medicine that utilises simultaneous data acquisition at different energy levels using two rows of detectors. This technique provides several interesting applications which improve insights into tissue composition. One implementation is the generation of virtual non-contrast (VNC) images from post-contrast spectral CT data by identifying and subtracting iodine pixels. Preliminary studies suggest that VNC images may offer diagnostic quality comparable to true unenhanced (TUE) images in healthy dogs; however, this technique has yet to be evaluated in clinical patients. This study compared the Hounsfield units (HUs) measured in VNC to those in TUE images of canine hepatic pathologies, taking into account specific types of pathologies based on their imaging characteristics. The attenuation values of the VNC and TUE series were analysed using two one-sided t-tests (TOST), and the signal-to-noise ratio (SNR) was calculated for each region of interest (ROI). A 5-point Likert scale was utilised to assess image noise, quality, and iodine subtraction in the VNC images. A total of 287 ROIs were analysed in the liver, gallbladder, paravertebral muscle, and pancreatic body of 28 dogs with histopathologically confirmed hepatic pathologies. 92.61% of the hepatic ROIs displayed a “negligible” difference of ≤10 HUs between VNC and TUE images, with significant p-values of <0.05 maintained for all ROIs within the limit of ≤10 HUs in the TOST, confirming equivalence between the two imaging modalities. The image quality assessment indicated that SDCT-derived images provided equal or superior quality compared to conventional CT. Therefore, it can be concluded that VNC images calculated from SDCT data could be an alternative to conventional TUE images for hepatic pathologies. Full article

Hyperammonaemia in dogs is most frequently associated with hepatic encephalopathy caused by portosystemic shunting. This retrospective multicentre study aimed to investigate the prevalence of hyperammonaemia and hepatic encephalopathy in dogs with recent or ongoing epileptic seizures. Furthermore, we sought to evaluate if transient post-ictal hyperammonaemia as a sequela to seizure activity occurs, as reported in humans and recently in cats. The medical records of all dogs presented between 2014 and 2024 to ten AniCura Veterinary Hospitals in Sweden were retrospectively reviewed to obtain those with recent or ongoing epileptic seizures with concurrent analysis of ammonia. The records of 267 dogs were extracted for further review. Inclusion criteria included information regarding the description and characterisation of the seizures and the analysis of ammonia within 24 h after last reported seizure activity. Additionally, hepatic function tests were required in dogs with elevated ammonia. In total, 58 dogs fulfilled the inclusion criteria, and 10 of those dogs (17%) had hyperammonaemia. Three dogs had documented hepatopathy, and two of them had surgically corrected portosystemic shunts. In seven dogs, no definitive cause of hyperammonaemia could be established. Three of the seven dogs had no evidence of portosystemic shunts, and six had no laboratory evidence supporting acute liver failure. According to the findings in this retrospective study, hyperammonaemia in the absence of evident acute hepatic failure or portosystemic shunting can occur in dogs with epileptic seizures, indicating that other differentials than hepatic encephalopathy should be considered. This study could not confirm the hypothesis of hyperammonaemia being a transient consequence of seizures. Full article

Genome-wide paternal uniparental isodisomy mosaicism (GWpUPIDM) is an extremely rare condition characterized by varying proportions of an androgenetic cell line across different tissues. It is primarily associated with severe congenital hyperinsulinism (CHI), Beckwith–Wiedemann syndrome (BWS) stigmata, a high risk (69–79%) of developing neoplasia and, in some cases, additional manifestations of multilocus paternal imprinting disorders (MPIDs). We herein report the first Mexican/Latin American female patient GWpUPIDM presenting with non-syndromic CHI requiring subtotal pancreatectomy and persistent but unexplained asymptomatic diffuse hepatopathy. When she was 8.5 years old, whole-exome sequencing (WES) in blood revealed an unexpectedly high (~92%) proportion of regions of homozygosity. DNA profiling confirmed a single haploid set of paternal chromosomes in both biparental and androgenetic cell lines, with varying proportions of the androgenetic lineage in leukocytes (84%), resected pancreas (74%), buccal cells (47%), and hair follicles (0.7%). Additional WES trio analysis using gDNA from the patient’s buccal cells and blood samples from both parents revealed an allelic frequency of ~75% for the paternally inherited variant NM_000158.4(GBE1):c.555+1G>T [ClinVar:632422; dbSNP:rs759707498]. At age 8.5, the patient exhibited no clinical features of BWS, MPIDs, or neoplasia. However, she presented persistent hepatic abnormalities that warrant further investigation to rule out an unmasked glycogen storage disease type IV (OMIM#232500). Our findings emphasize the critical need for early diagnosis of GWpUPIDM using SNP-based microarray or WES with further confirmation through DNA profiling in patients presenting with CHI, placental mesenchymal dysplasia, BWS stigmata, or other MPID-related conditions, including neoplasia, to facilitate timely cancer surveillance and management. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most prevalent chronic hepatopathy and a leading precursor of hepatocellular carcinoma (HCC) worldwide. Initially attributed to insulin resistance (IR)-driven metabolic imbalance, recent insights highlight a multifactorial pathogenesis involving oxidative stress (OS), chronic inflammation, and immune dysregulation. The hepatic accumulation of free fatty acids (FFAs) initiates mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, culminating in lipotoxic intermediates and mitochondrial DNA damage. These damage-associated molecular patterns (DAMPs), together with gut-derived pathogen-associated molecular patterns (PAMPs), activate innate immune cells and amplify cytokine-mediated inflammation. Kupffer cell activation further exacerbates OS, while ROS-induced transcriptional pathways perpetuate inflammatory gene expression. Traditional immunity refers to the well-established dichotomy of innate and adaptive immune responses, where innate immunity provides immediate but non-specific defense, and adaptive immunity offers long-lasting, antigen-specific protection. However, a paradigm shift has occurred with the recognition of trained immunity (TI)—an adaptive-like memory response within innate immune cells that enables enhanced responses upon re-exposure to stimuli. Following non-specific antigenic stimulation, TI induces durable epigenetic and metabolic reprogramming, leading to heightened inflammatory responses and altered functional phenotypes. These rewired cells acquire the capacity to produce lipid mediators, cytokines, and matrix-modifying enzymes, reinforcing hepatic inflammation and fibrogenesis. In this context, the concept of immunometabolism has gained prominence, linking metabolic rewiring with immune dysfunction. This literature review provides an up-to-date synthesis of emerging evidence on immunometabolism and trained immunity as pathogenic drivers in MASLD. We discuss their roles in the transition from hepatic steatosis to steatohepatitis, fibrosis, and cirrhosis, and explore their contribution to the initiation and progression of MASLD-related HCC. Understanding these processes may reveal novel immunometabolic targets for therapeutic intervention. Full article

The present study aimed to evaluate the therapeutic benefits of a hybrid material based on gold nanoparticles and natural extracts on an experimental model of thioacetamide-induced (TAA) liver injury in rats. The nanomaterials were synthesized using a green method, with Cornus sanguinea L. extract as a reducing and capping agent (NPCS), and were then mixed with Vaccinium myrtillus L. (VL) extract in order to achieve a final mixture with enhanced properties (NPCS-VL). NPCSs were characterized using UV–vis spectrophotometry and transmission electron microscopy (TEM), which demonstrated the formation of spherical, stable gold nanoparticles with an average diameter of 20 nm. NPCS-VL’s hepatoprotective effects were evaluated through an analysis of oxidative stress, inflammation, hepatic cytolysis, histology assays, and TEM in comparison to silymarin on an animal model of thioacetamide (TAA)-induced toxic hepatitis. TAA administration determined hepatotoxicity, as it triggered redox imbalance, increased proinflammatory cytokine levels and alanine aminotransferase (ALAT) activity, and induced morphological and ultrastructural changes characteristic of liver fibrosis. In rats treated with NPCS-VL, all these pathological processes were attenuated, suggesting a potential antifibrotic effect of this hybrid bionanomaterial. Full article