Search Results (739)

Background/Objectives: Insulin clearance is a key determinant of circulating insulin availability, but its diurnal variation and relationship with circadian metabolic programs in metabolic dysfunction associated steatotic liver disease (MASLD) remain unclear. This study aimed to explore diurnal insulin clearance in humans and examine associated metabolic gene signatures in MASLD. Methods: A single-subject pilot assessment was performed to explore daytime-nighttime differences in insulin clearance rate (ICR) surrogate index, followed by evaluation using public hyperinsulinemic-euglycemic clamp datasets from healthy individuals and patients with MASLD. Public circadian transcriptomic datasets, spatial transcriptomic data, and a time course high-fat diet (HFD)-induced mouse dataset were integrated. A predefined panel of insulin clearance-related and circadian genes, including carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), insulin receptor (INSR), insulin-degrading enzyme (IDE), clock circadian regulator (CLOCK), basic helix-loop-helix ARNT like 1 (BMAL1), nuclear receptor subfamily 1 group D member 1/2 (NR1D1/2), period circadian regulator 1/2 (PER1/2), and cryptochrome 1/2 (CRY1/2), was analyzed. Results: The pilot assessment showed higher nighttime than daytime ICR, and independent clamp datasets showed a similar pattern in healthy individuals. In MASLD, nighttime ICR remained relatively higher, whereas overall insulin clearance was reduced compared with controls. Human blood-based circadian transcriptomic datasets identified rhythmic expression patterns of selected genes involved in insulin clearance and circadian regulation, including CEACAM1, CLOCK, NR1D1, CRY1, PER1, and PER2. MASLD liver datasets showed reduced expression of insulin clearance-related and circadian genes, while spatial transcriptomics suggested altered lobular distribution of these signatures. In HFD mouse model, rhythmic expression of selected genes was attenuated. Conclusions: These integrative findings suggest that insulin clearance may exhibit diurnal variation and may be linked to circadian metabolic gene signatures across systemic and hepatic datasets in MASLD. Larger controlled human studies are needed to validate the temporal regulation of insulin clearance and its metabolic relevance. Full article

Chronic hepatitis B virus (CHB) infection remains a major cause of hepatocellular carcinoma (HCC), yet the premalignant microenvironment that links to HBV-associated HCC (HBV-HCC) is still poorly defined. This review synthesizes evidence that HBV-infected hepatocytes function as signaling hubs that, through microRNA (miRNA)-regulated crosstalk with Kupffer cells, liver sinusoidal endothelial cells, hepatic stellate cells and cancer-associated fibroblasts (CAFs), progressively remodel the liver from an antiviral tissue into a premalignant and early tumor microenvironment. Across the HBV-HCC continuum, a core set of dysregulated miRNAs, including miR-21, miR-29a/b, miR-122, miR-146a, miR-155, miR-200a, miR-126, miR-210 and the miR-130/301 family, coordinates transition from innate antiviral responses to HSC activation, extracellular matrix deposition, mechanotransduction, angiogenesis, chronic inflammation and cancer-associated CAF programing. By mapping these stage-specific miRNA networks onto acute infection, CHB, early fibrogenesis, advanced fibrosis and CAF-rich dysplastic states, the review reframes HBV-HCC pathogenesis as a sequence of miRNA-guided hepatocyte–stromal states rather than a purely hepatocyte-intrinsic process. This perspective suggests that composite, cell-type-resolved miRNA signatures in serum or liver tissue could serve as biomarkers for identifying CHB patients who are entering a premalignant microenvironment before conventional surveillance markers become abnormal. It further highlights miRNA hubs that couple antiviral, fibrogenic, angiogenic and CAF-associated signaling as potential therapeutic targets for reprograming the HBV-driven premalignant microenvironment, with the long-term goal of intercepting HBV-HCC development at earlier, microenvironmentally defined stages. Full article

Geranylgeranoic acid (GGA) is an endogenous acyclic diterpenoid metabolite of the mevalonate pathway that has been implicated in programmed cell death in hepatoma cells and may contribute to the elimination of premalignant hepatocytes. Recent metabolomic studies have identified 2,3-dihydrogeranylgeranoic acid (2,3-diGGA), an α-saturated derivative of GGA with reduced cell-death-inducing activity compared with GGA. This concise review examines the hypothesis that diversion of bioactive GGA toward 2,3-diGGA formation represents a metabolic shift that may attenuate hepatic tumor surveillance and influence hepatocellular carcinoma susceptibility. The review summarizes current evidence for endogenous GGA biosynthesis through the mevalonate pathway, MAO-B- and CYP3A4-associated GGA formation, and the tissue- and age-associated distribution of GGA and 2,3-diGGA. It also discusses the proposed 2,3-diGGA-forming activity, whose molecular identity remains unknown, and evaluates the potential utility of the GGA/2,3-diGGA ratio as a candidate biomarker. Finally, future experimental strategies are outlined to identify the responsible enzyme, clarify causality in cellular and animal models, and validate this metabolic framework in human liver tissues, chronic liver disease cohorts, and HCC-associated settings. Full article

Background/Objectives: Social determinants of health are implicated in metabolic dysfunction–associated steatotic liver disease (MASLD), yet longitudinal evidence on incident disease is scarce, and whether individual- and community-level determinants act independently remains unclear. The objective of this study was to examine whether individual food insecurity and neighborhood deprivation are independently associated with incident MASLD. Methods: In this retrospective cohort of 40,693 U.S. adults without baseline MASLD in the diverse NIH All of Us Research Program, food insecurity (two-item Hunger Vital Sign) and neighborhood deprivation (validated five-domain composite) were co-primary exposures, with incident MASLD ascertained from validated diagnostic codes. Proportional hazards models were adjusted for demographic, socioeconomic, and metabolic factors, including obesity. Results: Over 116,220 person-years, 1240 (3.0%) participants developed MASLD. Both associations remained significant after adjustment for demographic, socioeconomic, and major metabolic risk factors, including obesity (food insecurity adjusted hazard ratio [aHR] 1.32, 95% CI 1.13–1.53; neighborhood deprivation aHR 1.20, 95% CI 1.05–1.37). Unadjusted cumulative incidence was highest among participants with both exposures and lowest among those with neither. Findings were consistent across sensitivity analyses; the food-insecurity association remained when neighborhood disadvantage was specified with a census-based index. Conclusions: Food insecurity and neighborhood deprivation were independently associated with higher incidence of MASLD. Nutrition-focused, equity-oriented interventions warrant evaluation to reduce MASLD burden and advance health equity. Full article

The liver is an immunologically distinctive organ. Portal blood continuously delivers gut-derived antigens and microbial products, requiring hepatic immunity to balance surveillance with restraint. In hepatocellular carcinoma (HCC), this physiology is commonly overlaid by chronic injury, inflammation, and fibrosis, so the background liver forms part of the disease context in which the tumor microenvironment (TME) develops. This review synthesizes how cellular architecture, tumor-intrinsic programs, and structural, metabolic, and microbial conditions interact to shape immune evasion and heterogeneity. HCC provides the principal evidence base, with intrahepatic cholangiocarcinoma (iCCA) used as a structured, biologically distinct comparator. We organize therapies by the microenvironmental barriers they are intended to modify and distinguish established clinical efficacy from evidence that the proposed mechanisms mediate treatment benefit. Single-cell and spatial studies have resolved cellular states and spatial arrangements, including onco-fetal endothelial–myeloid neighborhoods and a macrophage–fibroblast boundary band separating lymphocyte-rich stroma from malignant tissue. These patterns operate within fibrotic and metabolically altered tissue and vary by etiology, spatial context, and tumor type. Vascular endothelial growth factor blockade with immune checkpoint inhibition and dual checkpoint blockade are established first-line options in advanced HCC. Chemo-immunotherapy is established in biliary tract cancer, and IDH1 inhibition has established efficacy in IDH1-mutant cholangiocarcinoma. Myeloid- and stroma-directed strategies, natural-product approaches, and engineered-cell therapies remain preclinical or early clinical. None of the pivotal trials tested whether the proposed microenvironmental mechanism mediated treatment benefit. The liver TME informs treatment selection without yet determining it. Full article

Estuarine and river-influenced coastal ecosystems are recognized as important sinks and channels for transfer of heavy metals into the marine environment. Continuous intake of metal pollutants could create chronic exposure situations, perhaps leading to molecular and cellular damage to resident biota, even if environmental concentrations are within regulatory limits. Thus, the incorporation of molecular and genotoxicity biomarkers into environmental monitoring programs has received growing interest, as changes in gene expression are among the earliest detectable responses to pollutant stress and may precede genotoxic effects, including DNA damage, at higher or prolonged levels of contaminant exposure. The present study aimed to determine the levels of heavy metals in the coastal zone where the Deliçay River flows into the Gulf of Iskenderun in the extreme northeastern Mediterranean Sea, Türkiye, and to investigate the genotoxic effects in the euryhaline ray-finned fish golden grey mullet (Chelon auratus). In this study, seasonal water samples (n = 3 per site per season) and C. auratus specimens (n = 10 per site per season; total n = 80) were collected from a reference site and the Deliçay estuary. Water samples were analyzed for metals (cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb), and zinc (Zn)) and fish samples were analyzed with the micronucleus (MN) test for determining nuclear abnormalities and the comet test for DNA damage levels. The concentrations of Fe, Zn, and Pb in seawater exceeded the Criterion Continuous Concentration (CCC) thresholds during the summer and autumn seasons, as well as in terms of annual mean values, indicating a potential chronic ecological risk to marine organisms. From the results of the micronucleus test performed in the present study, the highest MN frequencies (10.16 ± 0.15%) and other erythrocytic nuclear anomalies [kidney-shaped (10.36 ± 0.32%), binucleated (14.20 ± 0.10%), notched (14.63 ± 0.20%), lobed (15.43 ± 0.11%), and budded (15.33 ± 0.15%)] were found along the studied coastal zone in summer season. Results of the comet test, supporting the micronucleus test results, showed the highest percentages of DNA damage determined in all seasons in the gill and liver tissues of fish sampled in the studied coastal zone. This study is the first to evaluate the effects of heavy metal-induced genotoxic stress on ecological integrity in this coastal zone using a biomarker-based approach, and the results underscore the need for comprehensive environmental monitoring and pollution reduction strategies to protect ecosystem health. Full article

Background: Evidence regarding implementation of robotic liver surgery outside academic centers remains limited. This study evaluated perioperative, economic, and learning-curve outcomes during implementation of robotic liver surgery in a municipal hospital. Methods: Consecutive liver resections performed between November 2023 and June 2025 were retrospectively analyzed from an institutional database using propensity score matching. Primary outcomes included Textbook Outcome (TO), major complications (Clavien–Dindo ≥ IIIa), operative duration, blood loss, and postoperative quality of life (QoL). Learning curves were analyzed using cumulative sum analysis adjusted for IWATE difficulty levels. An economic subgroup analysis evaluated cost components. Results: After matching, operative duration, TO, and major complications were similar between groups, whereas blood loss was significantly lower in the robotic group. Risk-adjusted learning curves demonstrated outcome-specific change-points, with the lowest TO rates observed at 8 cases and peak major complication rates at 29 cases. QoL did not differ between groups. Total costs were comparable. Conclusions: Implementation of robotic liver surgery was associated with lower blood loss, but no statistically significant differences in the other principal clinical outcomes, total costs, or QoL. Complexity-adjusted learning curves demonstrated multidimensional learning patterns with different breakpoints across evaluated outcomes. Full article

Ferulic acid, a natural phenolic phytotherapeutic, which is mainly found in plant cell walls, has attracted the attention of researchers for its multiple pharmacological properties, especially for its anti-tumor potential. As an efficient antioxidant, the compound counteracts oxidative stress and modulates key molecular pathways involved in carcinogenesis. Recent studies demonstrate that ferulic acid exerts antiproliferative, pro-apoptotic, and anti-metastatic effects in various tumor models, including colon, breast, liver, and lung cancers. Mechanistically, ferulic acid affects components of prosurvival-signaling pathways such as PI3K/Akt, MAPK, and NF-κB, and stimulates programmed cell death by diverse mechanisms, including apoptosis, autophagy and ferroptosis. Furthermore, its ability to sensitize cancer cells to chemotherapeutic drugs with low toxicity to normal cells underscores its therapeutic potential. Despite promising preclinical anti-tumor activity, low water solubility and bioavailability limit its clinical use. For this reason, several attempts, ranging from chemical derivatives to nanodevices, have been made to improve ferulic bioavailability and anti-tumor efficacy. This review highlights the most significant and recent strategies to ameliorate the anticancer ability of ferulic acid in the perspective of a clinical application. Full article

Visceral white-nodules disease (VWND), caused by Pseudomonas plecoglossicida, poses a severe threat to the large yellow croaker (Larimichthys crocea) aquaculture industry. Although breeding resistant strains is a promising strategy, the molecular basis of disease resistance in this host remains poorly understood. Here, 1500 fish were artificially infected, and extreme phenotypes (30 resistant, RL; 30 susceptible, SL) were selected based on survival time and liver pathogen load. Liver histopathology revealed that RL fish maintained intact architecture with only mild vacuolation, whereas SL fish exhibited widespread necrosis, inflammation, and hemosiderin deposition. Consistently, RL fish showed lower MDA levels and higher GSH-Px activity and TAC. Transcriptomic analysis identified 172 differentially expressed genes (DEGs): RL fish were characterized by upregulation of anti-inflammatory and tissue-protective genes (Epo, CAV3) and downregulation of pro-coagulant factors (PAI1, K1kb1). Proteomic analysis identified 111 differentially expressed proteins, with significantly enriched pathways including the peroxisome, pentose phosphate, and phagosome pathways. Integrated cross-omics analysis revealed eight co-enriched KEGG pathways; among them, arginine/proline metabolism, phagosome, oxidative phosphorylation, and focal adhesion were consistently upregulated in the RL group. These findings suggest that effective resistance to VWND in L. crocea may involve a coordinated, multi-layered defense program encompassing redox balance, regulated immune responses, metabolic reprogramming, and cellular homeostasis. Cross-omics-supported candidate factors (e.g., P4ha1, COX6B, RAB5A, CAV3) represent promising targets for functional validation via DNA-level experiments in independent sample sets, and the prominent enrichment of arginine-proline metabolism indicates a potential target for dietary intervention that merits further investigation. Full article

Background/Objectives: Cystic echinococcosis (CE) remains endemic in many regions worldwide, including Jordan. It is one of the three zoonotic infections caused by the tapeworm of the genus Echinococcus. The epidemiology of CE in Jordan remains poorly defined, with systematic national investigations being absent for the past three decades. International Classification of Diseases (ICD) is a universal coding system for disease archiving within healthcare facilities. This coding system is utilized by the Hakeem program, a health informatics system that includes all Ministry of Health (MOH) hospitals and medical centers in Jordan. In this study, we assessed the frequency, plausibility, internal consistency, and administrative limitations of CE-related ICD codes within the MOH database, which have never been tested, and determined the validity of using the administrative data for epidemiological studies of CE in the future. Methods: A retrospective database study was conducted, using 12 echinococcosis-related ICD codes for electronic health record review. Data were retrieved from the Hakeem program. Unique patient entries recorded between 2010 and 2024 were extracted, and descriptive analytical methods were applied. Results: Over a 15-year period, 45,702 echinococcosis-related entries were reported across 178 healthcare facilities, with Amman accounting for the majority (59.1%) of reported entries. Entry numbers rose in the first 10 years (2010–2019) before a measurable decline and fluctuations in the following 5 years (2020–2024). Entries spanned all age groups, with middle-aged adults being the most frequently reported age group (42.45%). Females accounted for 74.4% of entries, reflecting a marked female predominance among coded entries. The most commonly reported ICD code was B67.8 (unspecified echinococcosis of the liver, 64.22%), followed by B67.5 (Echinococcus multilocularis infection of the liver, 33.57%). Confirmatory diagnostic data could not be extracted from the coding system. As a result, clinical validation could not be performed. Conclusions: The high frequency of echinococcosis-related entries suggests artificial inflation of CE-related codes, along with other data anomalies, reflecting internal inconsistencies and epidemiological implausibility of the administrative data within the Hakeem program. MOH should implement a dual, system-user-level plan to improve CE-related coding in the future. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver injury ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), a progressive inflammatory state associated with hepatocyte injury, fibrosis, cirrhosis, and hepatocellular carcinoma. Increasing evidence suggests that progression to MASH is not spatially uniform across the liver. Instead, it reflects region-specific metabolic stress, inflammatory signaling, and fibrogenic remodeling along the porto-central axis of the hepatic lobule. Recent advances in spatial transcriptomics, lipidomics, proteomics, and multiplex imaging have provided new insight into how hepatocytes, immune cells, endothelial cells, and hepatic stellate cells interact within distinct hepatic microenvironments during disease progression. In this review, we discuss emerging concepts linking hepatic zonation to steatosis, inflammation, fibrosis, and extracellular matrix remodeling in MASLD and MASH. We highlight how disruption of normal lobular organization contributes to a progressive loss of metabolic compartmentalization and to the amplification of inflammatory and fibrogenic signaling. We additionally examine how spatial disease programs differ between adult and pediatric MASLD, particularly given the periportal-predominant injury patterns frequently observed in children and the current lack of pediatric-focused mechanistic studies. Finally, we discuss recently approved therapies and emerging therapeutic strategies within the context of hepatic microenvironment remodeling and disease heterogeneity. Collectively, these findings support a framework in which MASLD and MASH are spatially organized diseases driven by dynamic multicellular interactions, emphasizing the importance of incorporating zonation and tissue context into future mechanistic studies and therapeutic development. Full article

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to evaluate the effectiveness and safety of first-line STRIDE therapy in patients with unresectable HCC treated in routine clinical practice. Methods: We conducted a retrospective multicenter study including patients with unresectable HCC who received first-line durvalumab plus tremelimumab through the Turkish national Early Access Program across 18 oncology centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and exploratory Cox regression analyses were performed to evaluate baseline prognostic factors. Results: Thirty-two patients were included. The median PFS was 7.25 months (95% CI, 3.68–22.29), and the median OS was 11.43 months (95% CI, 4.50–not reached). The underlying liver disease etiology was non-viral in 53.1% of patients, hepatitis B virus in 40.6%, and hepatitis C virus in 6.3%. Grade ≥ 3 treatment-related adverse events occurred in fewer than 10% of patients. Conclusions: In this multicenter real-world cohort, first-line durvalumab plus tremelimumab appeared to be a feasible treatment option and was generally well tolerated in patients with unresectable HCC. However, given the retrospective design, small sample size, and absence of a control group, these findings should be interpreted cautiously and require confirmation in larger prospective comparative studies. Full article

Background/Objectives: The developmental origins of health and disease (DOHaD) theory suggests that intrauterine and early postnatal life represents a critical window for programming lifelong health trajectories and disease susceptibility in offspring. Maternal nutritional imbalance during this period is closely associated with obstetric complications and an elevated risk of metabolic disorders in children. As central metabolic hubs, mitochondria constitute a critical axis linking adverse in utero exposure to metabolic defects in offspring across generations. Methods: In this narrative review, we searched PubMed and Web of Science (up to 8 July 2026) for English-language literature linking maternal metabolic conditions and mitochondrial dysfunction. We included in vivo, in vitro, and clinical studies, explicitly excluding primary inherited mtDNA mutations and nonnutritional toxicant exposures to isolate nutritional programming effects. Results: Maternal metabolic stress induces multifaceted, tissue-specific mitochondrial alterations in the developing offspring. Rather than a uniform systemic decline, mitochondrial reprogramming exhibits profound spatial and cellular heterogeneity across critical metabolic organs, including the placenta, liver, skeletal muscle, heart, and hypothalamus. These developmental adaptations often manifest as molecular compensations, such as altered mitochondrial dynamics, perturbed biogenesis, and shifted OXPHOS capacity, ultimately leading to functional bioenergetic failure, oxidative stress, and the establishment of insulin resistance. Discussion: Organ-specific mitochondrial dysfunction drives the maternal transmission of metabolic syndrome. Targeting these mechanisms via dietary modifications, exercise, pharmacological agents, and mitochondrial transplantation offers promising strategies to rescue bioenergetics and prevent metabolic diseases in offspring. Full article

Background/Objectives: Sacituzumab govitecan (SG, IMMU-132) is a TROP2-directed antibody–drug conjugate carrying SN-38. Patients with colorectal liver metastasis (CRLM) still have limited treatment options after first-line systemic therapy, and the preclinical pharmacological value of TROP2-directed SN-38 delivery in CRLM remains insufficiently defined. Methods: Public single-cell RNA-sequencing data were reanalyzed to explore the distribution of TACSTD2/TROP2-positive epithelial-associated cells in adjacent normal tissues, primary colorectal cancer, and CRLM. The prognostic relevance of TACSTD2 was evaluated using the Kaplan–Meier Plotter database. TROP2-knockdown and TROP2-overexpressing colorectal cancer models were used to assess IMMU-132 response in vitro and in vivo. Pharmacological antitumor activity was further evaluated using subcutaneous xenografts, syngeneic intrasplenic liver metastasis models, and CRLM patient-derived organoids (PDOs). Transcriptomic profiling and γ-H2AX immunofluorescence were used to explore treatment-associated molecular changes. Results: At the patient/sample level, TACSTD2/TROP2-positive epithelial-associated cells showed numerically higher proportions in primary colorectal tumors and liver metastases than in adjacent normal tissues, and high TACSTD2 expression was associated with inferior overall survival in a public survival database. TROP2 knockdown attenuated IMMU-132-induced growth inhibition, apoptosis, and suppression of colony formation. In vivo, IMMU-132 suppressed colorectal tumor growth and reduced liver metastatic burden, with more evident activity in human TROP2-overexpressing models. In a limited exploratory CRLM PDO cohort established after first-line therapy, liver metastasis-derived PDOs showed lower normalized AUC values than primary tumor-derived PDOs. Transcriptomic analysis and representative γ-H2AX immunofluorescence suggested that IMMU-132 treatment was associated with changes in adhesion/cytoskeletal-related pathways, Wnt/cancer-associated transcriptional programs, and DNA damage-associated signals. Conclusions: These in vitro, in vivo, and PDO-based findings support further preclinical pharmacological evaluation of TROP2-directed SN-38 delivery by IMMU-132 in biomarker-annotated CRLM models, particularly in the post-first-line systemic therapy setting. Full article

This study aimed to determine the prevalence of the liver trematodes Fasciola spp. and Dicrocoelium dendriticum in cattle and sheep slaughtered in Siirt Province using fecal sedimentation and postmortem liver examination to compare their detection performance, and to estimate the sensitivity of fecal sedimentation relative to postmortem examination. A total of 2211 animals, comprising 374 cattle and 1837 sheep, slaughtered during the study period, were included in the study. Fecal samples were collected rectally before slaughter, and after slaughter, the liver, gallbladder, and bile ducts were examined macroscopically. Fecal samples were analyzed using sedimentation; postmortem examination was the reference method. Based on postmortem examination, Fasciola spp. and D. dendriticum were detected in 26.2% (98/374) and 7.2% (27/374) of cattle, and in 14.8% (271/1837) and 5.9% (108/1837) of sheep, respectively. Fecal examination detected significantly fewer infections for both parasites in both hosts (McNemar test, p < 0.001 for all comparisons). The sensitivity of fecal sedimentation was 80.6% for Fasciola spp. and 29.6% for D. dendriticum in cattle, and 86.7% and 73.1%, respectively, in sheep. The prevalence of Fasciola spp. was significantly higher in cattle than in sheep (OR = 2.05, 95% CI: 1.58–2.67; p < 0.001), whereas the difference in D. dendriticum prevalence between cattle and sheep was not statistically significant (OR = 1.24, 95% CI: 0.80–1.92; p = 0.274). In cattle, age older than two years was significantly associated with Fasciola spp. (adjusted OR = 15.82, 95% CI: 8.12–30.84; p < 0.001) and D. dendriticum infection (adjusted OR = 3.29, 95% CI: 1.36–7.96; p = 0.008). In sheep, the Morkaraman breed had lower odds of Fasciola spp. infection (adjusted OR = 0.42, 95% CI: 0.32–0.56; p < 0.001) and D. dendriticum infection (adjusted OR = 0.23, 95% CI: 0.14–0.38; p < 0.001) than the Akkaraman breed, while age was significantly associated only with D. dendriticum infection (adjusted OR = 1.84, 95% CI: 1.25–2.71; p = 0.002). These findings demonstrate that liver trematode infections were common among slaughtered animals in Siirt. Reliance on fecal sedimentation may considerably underestimate prevalence, particularly for D. dendriticum in cattle. Age- and breed-related associations should be considered in surveillance and control programs. From a public health perspective, awareness of zoonotic fasciolosis and risks associated with consuming raw aquatic plants from potentially contaminated areas should be increased. Full article