Search Results (1,561)

Background: Emergency Department (ED) viral hepatitis screening programs typically report short-term outcomes. We evaluated the medium-term impact of an ED-based screening for Hepatitis C (HCV), Hepatitis B (HBV), and Hepatitis D (HDV) viruses. Methods: Prospective opportunistic screening conducted between January 2020 and December 2024 at a referral hospital in Barcelona. Adults attending the ED were screened for HBV, HCV, and HDV. Positive cases were evaluated and linked to care when appropriate. To assess screening impact, HCV RNA and HBsAg prevalences were compared between 2020–2021 and 2023–2024 among participants aged ≤80 years. Results: Over five years, 39,532 individuals were screened: 220 (0.56%) had detectable HCV RNA, 234 (0.59%) HBsAg, and 4 HDV RNA. Of 110 patients with detectable HCV RNA eligible for linkage, 84 (76%) were treated and cured. Among 135 HBV-positive individuals eligible for linkage, 116 (86%) attended outpatient follow-up. HCV RNA prevalence significantly decreased (0.58% vs. 0.35%, p = 0.005), whereas HBsAg prevalence did not vary (0.7% vs. 0.58%, p = 0.224). Conclusions: Sustained ED-based screening enabled the identification and linkage to care of several individuals with HBV and HCV. This strategy contributed to a reduction in HCV prevalence among ED attendees and supports opportunistic ED screening in viral hepatitis elimination goals. Full article

Introduction. Statins’ established cardiovascular benefits are often undermined by hepatic adverse effects in obese diabetic patients with suspected non-alcoholic fatty liver disease. We evaluated whether cannabis plant treatment is a safe and effective alternative to atorvastatin in a metabolically challenged rodent model. Methods. Fourteen obese and diabetic Wistar rats received either atorvastatin for 30 days or cannabis plant extract for 30 days. Main outcome: lipid profile; secondary outcomes: renal function, glycemia and endothelial health assessed through atherogenic indices. Safety was assessed using plasma liver enzyme concentrations. Results. Baseline biochemical profiles were similar between groups. Atorvastatin increased HDL-Col more than cannabis plant (MD: 44.3; IQR [33, 57.5] mg/dL, Hedges’ g 2.713 vs. MD: 14.3; IQR [14, 17] mg/dL, Hedges’ g 5.049), and cannabis plant did not change LDL-Col. Atherogenic index of plasma and Castelli Risk Index 1 improved with both interventions, more so with atorvastatin. Liver enzymes increased with atorvastatin (ALAT, MD: 15.9; IQR [12.5, 19.5] U/L; ASAT, MD: 33; IQR [26.5, 38] U/L) but remained virtually unchanged with cannabis. Serum creatinine increased with cannabis plant, with moderate effect size (Hedges’ g 0.798), but negligibly with statins (Hedges’ g 0.122). Conclusions. Cannabis plant extract modestly improved the lipid profile and atherogenic indices, with differences often not exceeding the change in control groups. Despite apparent liver safety, the undesired renal and neurological consequences limit applicability in humans. Further studies should prioritize addiction development and renal function. Full article

This study aimed to explore the protective mechanism of silybin against heat stress-induced liver injury in Peking ducks as a result of oxidative stress, inflammation, and lipid metabolism. One hundred and ninety-five 1-day-old healthy male Peking ducks with similar body weights were randomly divided into a control group, a heat-stress group, and three intervention groups treated with 400, 800, and 1600 mg/kg silybin under heat-stress from 21 d to 35 d for two weeks. The function indices, oxidative stress, inflammatory factor levels, histopathological changes and non-targeted lipidomic profiling in liver as well as growth performance were evaluated. Results showed that silybin supplementation partially alleviated the heat-stress-induced decreases in average daily feed intake and body weight gain (p > 0.05). Silybin supplementation at 400 and 800 mg/kg significantly reduced the heat-stress-induced increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase (γ-GGT) (p < 0.05), whereas the effect of 1600 mg/kg silybin was not significant. Albumin (ALB) and globulin (GLB) levels were mainly improved in the 800 mg/kg group, and GLB was also increased in the 400 mg/kg group (p < 0.05). Silybin supplementation significantly improved hepatic antioxidant capacity, especially in the 400 and 800 mg/kg groups, as indicated by increased superoxide dismutase (SOD) activity and total antioxidant capacity (T-AOC), and decreased malondialdehyde (MDA) and reactive oxygen species (ROS) levels (p < 0.05). In addition, the 400 and 800 mg/kg groups showed more significant reductions in the pro-inflammatory factors IL-6 and TNF-α, while IL-10 was increased in silybin-supplemented groups (p < 0.05). Lipid metabolism disorders were improved through regulation of the sphingolipid and glycerophospholipid metabolism pathways, while it alleviated heat stress damage by reducing the expression of heat shock proteins. In conclusion, silybin holds promise as an effective feed additive to alleviate heat stress in poultry. This study provides a theoretical basis and practical approach for improving the health and productive performance of Peking ducks under heat-stress conditions. Full article

Deoxynivalenol (DON) and patulin (PAT) are common mycotoxins in cereals and fruits, posing health risks for animals and human beings. In order to study their liver toxicity, 24 mice were randomly assigned to four groups, with six replicates in each group (one mouse per cage). The mice were intragastrically administered with DON, PAT, DON + PAT (DP), or without DON and PAT (the control group) for 28 days, respectively. The results showed that body weight gain was significantly reduced by all toxin treatments, compared with the control group, and the lowest body weight gain was observed in the DP group. Histopathology revealed that hepatocyte damage and inflammatory infiltration were more serious in the DP group, exhibiting the highest mRNA abundances of MyD88, IFN-γ, and JAK2. The severity of hepatocyte apoptosis induced in each group followed the order: DON > DP > PAT; the severity of oxidative stress was ranked as DP > DON > PAT. Transcriptomic analysis revealed that numerous differentially expressed genes were regulated by DP treatment, which were mainly enriched in the MAPK, JAK-STAT, and transforming growth factor (TGF)-β signaling pathways. In conclusion, individual exposure to DON or PAT triggered hepatic injury, and their co-exposure further exacerbated liver damage. Full article

Background: Berberine, an isoquinoline alkaloid present in Berberis spp., Coptis chinensis and Hydrastis canadensis, is among the most widely consumed metabolic-health supplements, popularized as “nature’s Ozempic”. Concurrent, often undisclosed use with prescription drugs is common in older adults, yet berberine is far from inert. Objective: To synthesize the evidence on berberine as a perpetrator of supplement–drug interactions, propose a four-axis mechanistic taxonomy, with product quality treated separately as a modifier of exposure rather than as a mechanism, and derive a clinically actionable risk-stratification framework. Methods: Structured narrative review, prepared per the SANRA quality criteria; PubMed/MEDLINE, Scopus, Web of Science and Embase were searched up to May 2026. Results: Despite very low systemic exposure (oral bioavailability 0.68% in rats; low ng/mL plasma concentrations in humans), high luminal, enterocytic and hepatic concentrations generate interaction liability, documented in humans for a few pairs and mechanistic for most, along four mechanistic axes: inhibition, and transcriptional induction, of CYP3A4, with CYP2D6/CYP2C9 inhibition that is quasi-irreversible through a metabolite-intermediate complex; transporter modulation (P-glycoprotein, OCT1/OCT2, and MATE1); pharmacodynamic additivity (hypoglycemia, hypotension, and QT prolongation); and microbiome- and gut-barrier-mediated effects, the last of these being a candidate axis rather than a demonstrated one. Product-quality variability is treated separately, as a modifier of exposure. The clinical anchor is increased cyclosporine exposure in renal-transplant recipients (AUC +34.5%; trough 29.3% above control). These elements are integrated into a three-tier risk-stratification framework that combines perpetrator potency, victim-drug vulnerability, and patient vulnerability, with each tier being linked to a defined pharmacy action. Conclusions: In patients on multiple medications, and particularly when berberine is co-administered with drugs of narrow therapeutic index, it should be managed as an active pharmacological perpetrator rather than as an inert supplement. Unstandardized product quality and an unsettled European regulatory framework, under which national limits differ by more than an order of magnitude, further widen the uncertainty around the dose actually delivered. Berberine use should therefore be elicited routinely at medication reconciliation and stratified by mechanism, by victim-drug vulnerability, and by patient risk, with particular attention to metabolic self-medication in the GLP-1 era. Full article

A lifelong career devoted to the development of specific antiviral agents eventually yielded, besides (almost) 3000 publications, about ten antiviral compounds that were approved and marketed as antiviral drugs, i.e., DHPA (Duviragel^®), BVDU (Zostex^®, Mevir^®, Brivir^®…), VACV (Zelitrex^®, Valtrex^®), d4T (Stavudine^®), emivirine (Coactinon^®), rilpivirine (Edurant^®), HPMPC (Vistide^®), PMEA (Hepsera^®), tenofovir (Viread^®) and AMD-3100 (Mozobil^®), with the latter as a hematopoietic stem cell mobilizer. The targeted viruses for these compounds were herpes simplex virus (HSV), varicella-zoster virus (VZV), cytomegalovirus (CMV), human immunodeficiency virus (HIV), and hepatitis B virus (HBV). For other viruses, such as filo-, rhabdo-, arena-, myxo-, polyoma- and papillomaviruses, strategies have been elaborated that should facilitate future developments of antiviral drugs. Full article

Background/Objectives: Vonoprazan is a potassium-competitive acid blocker with potential for the treatment of equine gastric ulcer syndrome. Vonoprazan metabolic pathways in horses have not been characterized. This study aimed to identify vonoprazan metabolites following oral administration and to determine the metabolic enzymes responsible for their metabolism using in vitro models. Methods: Six healthy adult Thoroughbred horses received vonoprazan (0.5 and 1 mg/kg PO) in a randomized crossover design. Plasma concentrations of vonoprazan-N-oxide (M-I) and vonoprazan-nitrone (M-III) were quantified using a validated liquid chromatography-tandem mass spectrometry method, and a non-compartmental pharmacokinetic analysis was performed. In vitro metabolism was evaluated using equine liver microsomes (ELMs) and equine recombinant CYP450 (eq-rCYP) enzymes. Enzyme kinetics were characterized using nonlinear regression modeling. Results: Both metabolites were detected in plasma after oral administration. Systemic exposure to M-I was markedly greater than M-III at both doses. At 1 mg/kg, mean ± SD C_max values were 39.2 ± 28.3 ng/mL for M-I and 1.67 ± 1.66 ng/mL for M-III. AUC_0–∞ increased dose-proportionally for both metabolites. In ELMs, M-I formation followed substrate inhibition kinetics, whereas M-III formation followed Michaelis–Menten kinetics. Among recombinant enzymes, CYP2D50 and CYP3A94 were the primary contributors to metabolite formation, exhibiting metabolite-specific kinetic profiles. Conclusions: These findings demonstrate that vonoprazan undergoes hepatic oxidative metabolism in horses, with M-I as the predominant circulating metabolite. Equine recombinants CYP2D50 and CYP3A94 appear to play central roles in equine vonoprazan metabolism, providing foundation for future evaluation of drug–drug interaction potential and clinical use in this species. Full article

Despite the traditional application of Sophora moorcroftiana (Benth.) Baker seeds for liver disorders, the capacity of its 70% ethanol extract (SMS) to alleviate metabolic dysfunction-associated steatotic liver disease (MASLD) and the underlying gut–liver axis mechanisms remain unclear. In this study, a high-fat diet (HFD)-induced MASLD mouse model was established to investigate the protective effects of SMS and its regulatory role in the interplay among gut microbiota, short-chain fatty acids (SCFAs), and inflammation. Serum, intestinal, and hepatic samples were collected to evaluate inflammatory responses, intestinal barrier integrity, and hepatic lipid metabolism. Gut microbiota composition and SCFA profiles were analyzed using 16S rRNA sequencing and metabolomics. In LPS-stimulated Caco-2 cells, SMS reduced inflammatory cytokines and TLR4/MyD88/NF-κB-associated signaling. The results demonstrated that SMS markedly alleviated hepatic steatosis by reducing triglyceride synthesis and hepatocellular lipid accumulation. In addition, SMS promoted the proliferation of beneficial bacteria, including Bifidobacterium and Akkermansia, and increased the production of SCFAs, particularly butyrate. SMS also restored intestinal barrier integrity through upregulation of Occludin and Claudin-1, thereby reducing circulating lipopolysaccharide (LPS) levels. Furthermore, SMS attenuated inflammation by inhibiting activation of the TLR4/NF-κB signaling pathway. Collectively, these findings demonstrate that SMS alleviates MASLD through coordinated modulation of gut microbiota composition, SCFA metabolism, intestinal barrier function, and inflammatory responses, highlighting its potential as a therapeutic strategy targeting the gut–liver axis. Full article

Background/Objectives: Magnesium (Mg) deficiency has been linked to various adverse health outcomes; however, its association with metabolic dysfunction-associated steatotic liver disease (MASLD) has not been fully elucidated. This study examined the association of serum Mg levels with MASLD in Korean adults. Methods: We analyzed a nationwide sample of 4952 adults in South Korea. Serum Mg levels (mg/dL) were measured. MASLD was defined as a hepatic steatosis index score of ≥36 together with the presence of cardiometabolic risk factor, including overweight/obesity, high fasting glucose, high blood pressure, high plasma triglycerides, or low plasma HDL cholesterol. The association between serum Mg levels and MASLD was examined using logistic regressions. Odds ratios (ORs) and 95% confidence intervals (CIs) were determined. Results: The mean (standard deviation [SD]) serum Mg level was 2.13 (0.15) mg/dL. The prevalence of MASLD was 25.7%. After adjusting for the sociodemographic variables, the OR (95% CI) for the association between a 1–SD increment in serum Mg levels and MASLD was 0.90 (0.84–0.96, p = 0.004). Conclusions: This nationally representative cross-sectional study found that serum Mg levels were inversely associated with the likelihood of MASLD among adults in South Korea. Full article

Primary hepatic neoplasms in dogs, while uncommon, are occasionally associated with severe hypoglycemia, although the underlying mechanism may be difficult to establish. A 7-year-old castrated male Maltese dog weighing 3.6 kg was referred for recurrent bilateral pelvic limb weakness, episodic collapse, and abdominal distension. Severe hypoglycemia was documented, with a blood glucose concentration of 26 mg/dL. Computed tomography revealed a large mass arising from the right lateral liver lobe, with no identifiable pancreatic mass or distant metastasis. The serum insulin concentration measured during hypoglycemia was low at 1.0 μU/mL, making insulinoma less likely. Glycemic control temporarily or partially improved during prednisolone treatment; however, severe hypoglycemia recurred after prednisolone discontinuation before surgery. The hepatic mass was surgically excised. Dextrose-containing intravenous fluids were maintained for 6 h postoperatively, and no recurrent clinically significant hypoglycemia was documented after their discontinuation. Histopathologic examination revealed a poorly differentiated neoplasm with mesenchymal morphology, occasional cytoplasmic vacuolation, and no unequivocal lipoblasts. The neoplastic cells showed diffuse vimentin immunoreactivity, weak cytoplasmic S-100 immunoreactivity in a subset of cells, and no immunoreactivity for smooth-muscle actin or hepatocyte paraffin 1. These findings raised the possibility of adipocytic differentiation but were insufficient to establish a specific tumor lineage; therefore, the lesion was classified as a primary hepatic neoplasm of uncertain histogenesis. At 247 days after surgery, the dog remained normoglycemic without supplemental glucose or glucocorticoid treatment, and no imaging evidence of local recurrence or distant metastasis was identified. The postoperative course supported an association between the hepatic neoplasm and hypoinsulinemic hypoglycemia. Non-islet-cell tumor hypoglycemia was suspected but remained unconfirmed because an insulin-like growth factor-mediated mechanism was not demonstrated. Full article

This study evaluated whether chlorogenic acid (CGA) attenuates hepatic injury in broilers under high stocking density (HSD). A total of 216 experimental male Arbor Acres broilers were assigned to normal density without CGA (ND; 14 birds/m²), high density without CGA (HD; 22 birds/m²), normal density with 0.1% CGA (NDCGA), or high density with 0.1% CGA (HDCGA) groups, with six cages per treatment. CGA was supplied from day 7 to 42. At 42 d, live-weight densities were 35.00, 50.25, 34.48, and 49.38 kg/m², respectively. Compared with their corresponding normal-density groups, the high-density groups had lower body weights at 21, 28, 35, and 42 d, and lower average daily gain (ADG) during days 21–42 (p < 0.05), whereas CGA did not significantly alter body weight or ADG within either stocking density (p > 0.05). At 35 and 42 d, the HD group had lower hepatic T-AOC, SOD, and CAT activities and higher MDA content than the ND group (p < 0.05). Compared with the HD group, the HDCGA group had higher T-AOC and CAT activities and lower MDA content at both ages, and higher SOD activity at 42 d (p < 0.05). Qualitative histological and transcript-level alterations were evident at 28 d. Compared with HD, the HDCGA group showed treatment-associated shifts in AMPK, SREBP1, ACACA, PLA2G4A, COX-2, ALOX5, and NOX5 mRNA abundance (p < 0.05). Under the experimental conditions, 0.1% CGA was associated with partial attenuation of HSD-related hepatic oxidative, lipid-metabolic, and inflammatory disturbances without a significant growth response. Full article

The adult liver exhibits remarkable regenerative capacity in vivo; however, primary hepatocytes (PHs), the principal functional cells of the liver, swiftly forfeit their proliferative potential and specialized hepatic functions when isolated from their native microenvironment and cultured in vitro. While PHs are the benchmark for studying hepatic physiology, xenobiotic metabolism, and toxicological responses, their rapid dedifferentiation resulting in the loss of hepatic functions significantly limits their further application. Recent studies suggest three converging strategies to address the challenge of long-term maintenance and expansion of PHs. First, defined chemical and growth factor-based protocols can temporarily induce hepatocytes into a proliferative, progenitor-like state, followed by a maturation phase that restores differentiated hepatic functions. In addition, the inhibition of signaling pathways linked to cellular stress responses and identity loss can postpone dedifferentiation and preserve drug-metabolizing activity for prolonged durations, thereby enhancing disease modeling and toxicology studies. Finally, three-dimensional (3D) culture platforms generally improve hepatocyte maturation and functional stability, but these are often not scalable due to matrix dependence, technical complexity, handling requirements, and cost. This review thoroughly examines innovative methodological advancements designed to facilitate the proliferation and prolonged viability of healthy PHs, focusing on their translational relevance and clinical applicability. Full article

In drug-induced liver injury (DILI) prediction field, animal models and in vitro cell models are most commonly used. However, animal models require long experimental timelines and may exhibit species-specific differences compared with humans, whereas conventional two-dimensional (2D) cell culture models lack cell-to-cell and cell-to-extracellular matrix (ECM) interaction. Liver organoid models and liver organ-on-a-chip can better simulate the human liver microenvironment; however, the construction of liver organoids requires a long cycle and high costs, while liver organ-on-a-chip systems demand specialized equipment and professional technicians. Herein, we selected the human C3A cell line, characterized by its low cost and facile culture conditions to establish an in vitro three-dimensional (3D) liver model. Briefly, C3A cells were embedded in Matrigel and cultured for 7 days to allow model maturation. Compared with their 2D-cultured cell model, the established 3D model exhibited elevated mRNA expression levels of drug-metabolizing cytochrome P450 enzymes (CYPs). Moreover, the model displayed robust expression of key hepatic biomarkers, as well as bile duct biomarkers. To evaluate the model’s applicability for DILI prediction, we performed toxicity assessments using a panel of six well-characterized hepatotoxicants and three non-hepatotoxic compounds. Notably, the 3D C3A model achieved a sensitivity of 83.3%, specificity of 100%, and overall accuracy of 88.9%. Furthermore, treatment of this model with chlorpromazine, a well-characterized cholangiotoxic agent, resulted in suppressed expression of the bile duct biomarker cytokeratin 19 (CK19) and bile salt export pump (BSEP), accompanied by impaired bile acid transport capacity. Taken together, this study provided a simple, low-cost, easy to culture, and more readily scalable 3D hepatic model in comparison with conventional 2D primary human hepatocyte (PHHs) models and other advanced 3D liver models. Notably, the model displayed dual hepatic and biliary characteristics, supporting predictions of both DILI and drug-induced bile duct injury. It provided a promising in vitro platform for assessing drug-induced hepatobiliary toxicity, with potential to reduce reliance on animal experiments and accelerate early-stage screening of novel pharmaceutical candidates. Full article

Diets high in fat and refined carbohydrates reliably mimic key features of metabolic dysfunction-associated fatty liver disease (MAFLD), including hepatic lipid accumulation, oxidative stress, and ongoing liver injury. This study evaluated the long-term, low-dose administration of Callistemon citrinus ethanolic leaf extract and its primary bioactive compounds: d-limonene, ellagic acid, gallic acid, and p-coumaric acid to prevent lipotoxicity in rats fed a high-fat–sucrose diet (HFSD). Sixty male Wistar rats were randomly divided into 10 groups: normal control group, an untreated HFSD group, and eight HFSD groups treated for 23 weeks with metformin, C. citrinus extract, the individual bioactive compounds, or a mixture of these compounds. We assessed body and organ weights, liver macroscopic features, serum markers of liver injury, oxidative stress biomarkers, histopathological changes, and hepatic fatty acid profiles. HFSD feeding induced significant body weight gain, hepatomegaly, severe tissue damage, elevated serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), glucose and triglycerides, alongside heightened hepatic oxidative stress, and altered saturated fatty acid profiles. Conversely, treatment with metformin and the natural compounds attenuated HFSD-induced liver injury to varying degrees. Improvements in histopathological severity and serum liver enzymes correlated with decreased oxidative stress biomarkers. Notably, ellagic acid, gallic acid, d-limonene, and the bioactive mixture, significantly improved hepatic fatty acid profiles, whereas p-coumaric acid exhibited more modest effects. These results demonstrate that long-term administration of low-dose treatment can successfully improve all evaluated metabolic, biochemical, and histological parameter, suggesting that modulating oxidative stress and liver lipid composition is strongly linked to the mitigation of liver injury in this experimental MAFLD model. Full article

Hepatitis D virus (HDV) is a satellite virus that requires the presence of a helper virus, the hepatitis B virus (HBV). Soon after its discovery by Mario Rizzetto in 1977, severe outbreaks of fulminant hepatitis D occurred in the past century, in indigenous populations from the Western and Southern (Amazon) regions of Venezuela, while the indigenous population from the Eastern region (Orinoco Delta) has been found to be free of this virus. Data on the prevalence of HDV infection in Venezuela are still highly imprecise. The aim of this study is to provide insights into the current situation of this disease in the country. Evidence of exposure and infection with HDV was found again mainly in indigenous populations, although also one patient with hepatitis B from the capital was found to be infected with HDV genotype 1. The genotype found in the indigenous Bari population was HDV genotype 1, the same lineage (a putative new subgenotype 1j) previously identified in this region in both Venezuela and Colombia. Although scarce information is still available about the burden of HDV infection in Venezuela, the few studies available are consistent in showing an epidemic concentrated mainly in some, but not all, indigenous populations. Reflex testing is needed to have a better appraisal of this disease in the country. Full article