Search Results (602)

Methotrexate (MTX) is widely used for its chemotherapeutic and immunosuppressive properties, but is limited by oxidative stress-mediated hepatotoxicity. Nanoantioxidant delivery systems can enhance the stability, solubility, and in vivo efficacy of natural antioxidants. This study investigated the hepatoprotective effects of myricetin (MYR), a flavonoid with potent antioxidant activity, and its liposomal nanoantioxidant formulation (MYR-loaded liposomal nanoparticles, MYR-LNPs) against MTX-induced liver injury in male albino Sprague Dawley rats. Sixty rats were randomly allocated to six groups: control, MTX, MYR, MYR-LNPs, and combinations of MTX with MYR-LNPs. MYR-LNPs were successfully formulated and physicochemically characterized, exhibiting a mean particle size of 95.6 nm, a zeta potential of −32 mV, and a narrow polydispersity index, collectively confirming their colloidal stability and suitability for hepatic delivery. MTX markedly disrupted liver function, increasing serum AST, ALT, ALP, and bilirubin and decreasing total protein, albumin, and globulin, whereas co-treatment with MYR-LNPs substantially restored these parameters and outperformed free MYR. MTX-induced oxidative stress, reflected by depleted hepatic GSH and antioxidant enzymes (GPx, SOD, CAT, GST), elevated reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyls and downregulated NRF2/HO-1, was significantly counteracted by MYR-LNPs. In addition, MYR-LNPs mitigated MTX-evoked inflammation and nitrosative stress by reducing NF-κB, TNF-α, IL-1β, nitric oxide, and iNOS expression. They corrected apoptotic imbalance by lowering Bax and caspase 3 while increasing Bcl-2. Histopathological and ultrastructural assessments confirmed that MYR-LNPs preserved hepatic architecture and mitochondrial integrity. These findings indicate that MYR-loaded liposomal nanoantioxidants provide superior protection against MTX-induced hepatotoxicity by modulating oxidative stress, inflammation, and apoptosis, supporting their potential as an advanced nanodrug delivery strategy for antioxidant therapy. Full article

Adipose mesenchymal stem cell-derived exosomes (ADSC-Exo) have demonstrated therapeutic effects in liver diseases and injuries. The Augmenter of Liver Regeneration (ALR), a novel hepatic trophic growth factor, promotes hepatic structural and functional recovery. In this study, we constructed ALR-overexpressing ADSC-Exo (ADSC-ALR-Exo) by harnessing the messaging capacity of ADSC-Exo, and analyzed the effects of ADSC-ALR-Exo on hepatic ischemia–reperfusion injury (IRI) combined with partial hepatectomy in a minipig model. Our results indicated that, compared to the ADSC-Exo group, the ADSC-ALR-Exo group exhibited a significant reduction in reactive oxygen species (ROS) levels, alongside a notable increase in the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Furthermore, there was a marked decrease in malondialdehyde (MDA) content. Concurrently, the concentrations of pro-inflammatory factors in the blood (IL-1β, IL-18, and TNF-α) and liver tissue (IL-1β, IL-18, IL-6, and TNF-α) were significantly lower in the ADSC-ALR-Exo group, while the level of the anti-inflammatory factor IL-10 in the blood was significantly elevated. Additionally, ALR enrichment enhanced the inhibitory effect of ADSC-ALR-Exo on endoplasmic reticulum stress-related pathways, specifically ATF6, IRE1α, and PERK. Compared to ADSC-Exo, the ADSC-ALR-Exo intervention was also more effective in reducing the expression levels of NLRP3, caspase-1, and GSDMD, thereby decreasing the incidence of pyroptosis. In conclusion, ADSC-ALR-Exo mitigated liver injury by inhibiting endoplasmic reticulum stress and cellular pyroptosis induced by liver injury. Full article

Background: The CFTR modulator elexacaftor/tezacaftor/ivacaftor (ETI) has transformed cystic fibrosis (CF) care, but national-level real-world data on long-term effectiveness, durability of response, and treatment de-escalation remain limited. Methods: We conducted a nationwide longitudinal study using the Italian Cystic Fibrosis Registry. People with CF aged ≥6 years who initiated ETI between October 2019 and December 2022 and received ≥3 months of continuous therapy were included. Lung function (percent predicted FEV₁, ppFEV₁), nutritional status (BMI or BMI z-score), hospital days, complications, microbiology, and chronic treatments were assessed during the two years before and up to two years after ETI initiation. Longitudinal changes were analyzed using generalized estimating equations with multiple imputation for missing data. Results: The cohort included 2276 individuals (mean age 27.9 ± 13.3 years; 49% female). Mean ppFEV₁ declined during the pre-ETI period but increased by 9.9 percentage points at 12 months after ETI initiation (p < 0.001) and remained 6.8 percentage points above baseline at 24 months. A decline between 12 and 24 months was observed overall, except in individuals with severe baseline lung disease (ppFEV₁ < 40%), who maintained stable improvements. Mean annual hospital days decreased by approximately 65% and remained low throughout follow-up. Nutritional status improved, with a mean BMI increase of approximately 1.05 kg/m² compared with immediate pre-treatment in adults and a BMI z-score increase of 0.2 SD compared with pre-treatment timepoints in children. Use of most standard CF therapies declined substantially, particularly among individuals with ppFEV₁ ≥ 40%. The prevalence of allergic bronchopulmonary aspergillosis decreased, while liver disease prevalence increased modestly, largely reflecting transient elevations in liver enzymes. Conclusions: In this nationwide real-world cohort, ETI was associated with sustained improvements in lung function, nutritional status, and hospitalization burden. The attenuation of lung function gains after the first year, particularly in less severe disease, supports the need for individualized monitoring and cautious treatment de-escalation in the ETI era. Full article

Background: Statins have been associated with a reduced risk of primary liver cancer (PLC), primarily hepatocellular carcinoma (HCC). However, the optimal use for effective protection and whether benefits vary by patient characteristics remain unclear. We evaluated the association between statin use and PLC risk in metabolic-dysfunction-associated steatotic liver disease (MASLD), considering cumulative exposure and potential effect modifiers. Methods: We conducted a retrospective cohort study using the Veteran Affairs electronic health records. Patients with chronically elevated liver enzymes and metabolic dysfunction, without other chronic liver diseases, were identified between 2007 and 2009 and followed through 2019 for incident PLC. Statin exposure was assessed at baseline and during the follow-up, with dose standardization by LDL-lowering potency (simvastatin-equivalent units). Time to PLC was analyzed using Cox models adjusted for covariates, considering potential interactions. Results: Among 329,577 patients (92% male; median age 62 years), 0.82% developed PLC (median follow-up of 9.7 years). Baseline statin use showed a significantly lower PLC risk (adjusted hazard ratio 0.64; 95% CI, 0.57–0.71; p < 0.0001). No significant interaction was observed with age, sex, metabolic syndrome, or cirrhosis. Higher cumulative statin exposure demonstrated a dose-dependent risk reduction, remaining significant at simvastatin-equivalent doses > 15,561 mg annually after accounting for incident cirrhosis. Atorvastatin/rosuvastatin use provided comparable protection, despite different lipophilicity, and demonstrated stronger effects than others. Conclusions: In MASLD, statin therapy was associated with a dose-dependent PLC risk reduction. High-intensity therapy (simvastatin-equivalent > 40 mg daily) conferred substantial protection regardless of age, sex, insulin resistance, or cirrhosis, supporting a potential statin-based PLC chemoprevention in MASLD. Full article

Objectives: Doxorubicin, a widely used chemotherapeutic agent, is known to induce hepatotoxicity through oxidative stress and inflammatory pathways. Vitamin D has been reported to exert antioxidant and immunomodulatory effects; however, its potential protective role in doxorubicin-induced liver injury remains insufficiently characterized. Materials and Methods: Adult male Wistar albino rats were randomly assigned to six groups (n = 7): Control, Vitamin D (5000 IU/kg), Vitamin D (60,000 IU/kg), Doxorubicin, DOX + Vitamin D (5000 IU/kg), and DOX + Vitamin D (60,000 IU/kg). Vitamin D₃ (cholecalciferol) was administered orally either as a daily dose (5000 IU/kg for 12 days) or as a single bolus dose (60,000 IU/kg). Doxorubicin (6 mg/kg/day, cumulative dose 18 mg/kg) was administered intraperitoneally on days 10–12. Hepatic injury was evaluated using ⁹⁹mTc-pyrophosphate (⁹⁹mTc-PYP) scintigraphy, serum liver enzymes (AST, ALT, LDH, total bilirubin), renal markers (BUN, creatinine), calcium and 25-hydroxyvitamin D [25(OH)D], oxidative stress parameters (MDA, TOS, TAS, GSH, SOD, Nrf2), and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-10). Results: Doxorubicin markedly increased hepatic ⁹⁹mTc-PYP uptake and significantly elevated AST, ALT, LDH, bilirubin, MDA, TOS, TNF-α, IL-6, and IL-1β levels while reducing Nrf2, GSH, SOD, TAS, and IL-10 (all p < 0.001). Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D [25(OH)D] levels compared with controls (32.3 ± 2.7 vs. 74.1 ± 3.8 and 69.3 ± 3.2 ng/mL for the 5000 and 60,000 IU/kg groups, respectively; p < 0.001) and attenuated DOX-induced hepatic injury, as indicated by reduced radiotracer uptake and improved oxidative and inflammatory markers. Vitamin D also mitigated DOX-associated increases in renal injury markers (BUN and creatinine) without inducing hypercalcemia. No significant differences were observed between the two vitamin D dosing regimens in most outcome measures. Conclusion: Vitamin D supplementation exerted protective effects against doxorubicin-induced liver injury, likely through modulation of oxidative stress and inflammatory pathways. Additionally, ⁹⁹mTc-PYP scintigraphy may serve as a useful imaging tool for detecting acute hepatocellular injury and evaluating therapeutic responses. Full article

Obesity represents a heterogeneous metabolic disorder characterized by substantial interindividual variation in inflammatory status, insulin sensitivity, and cardiometabolic risk. Traditional anthropometric measures fail to capture this metabolic diversity, limiting risk stratification and personalized intervention strategies. This review critically examines nutritional and metabolic biomarkers that reflect the physiological dysregulation underlying obesity, including adipokines (leptin, adiponectin, resistin), inflammatory markers (C-reactive protein, interleukin-6, TNF-α), insulin resistance indices (HOMA-IR, fasting insulin, HbA1c), and lipid metabolism indicators (LDL cholesterol, triglycerides, HDL cholesterol, and liver enzymes such as ALT and GGT). Among these, elevated CRP, reduced adiponectin, and increased HOMA-IR have demonstrated the strongest clinical utility for early metabolic risk identification. We further evaluate emerging biomarkers—including circulating microRNAs, gut microbiota-derived metabolites (short-chain fatty acids, TMAO, lipopolysaccharides), and bile acid profiles—which offer additional mechanistic insight into diet–microbiome–host interactions. We systematically assess the mechanistic basis, clinical relevance, and nutritional modulation of each biomarker class, emphasizing how dietary composition—particularly fatty acid quality, fiber intake, and overall dietary patterns such as the Mediterranean diet—influences biomarker profiles and metabolic outcomes. Furthermore, we explore how biomarker-based phenotyping enables precision nutrition approaches by identifying individuals most likely to benefit from specific dietary interventions. Integration of multi-biomarker panels with clinical and genetic data holds promise for advancing from population-based dietary guidelines toward individualized nutrition strategies that optimize metabolic health and prevent obesity-related complications. Future research should prioritize validating biomarker-guided intervention frameworks, establishing standardized thresholds across diverse populations, and developing clinically implementable tools for personalized nutritional medicine. Full article

Background: Hepatic fibrosis and its progressive form, liver cirrhosis, are dangerously recognized complications of liver injury with limited treatment options. This study evaluated the hepatoprotective effects of ivabradine on thioacetamide (TAA)-induced hepatic fibrosis in rats. Methods: Rats were divided into five groups with 10 rats/group and treated as follows: normal, where rats received 0.5% CMC-Na solution orally; ivabradine control, where rats received only ivabradine (20 mg/kg, once daily, orally) for 6 weeks; TAA, where rats received an intraperitoneal (i.p.) injection of TAA (200 mg/kg) thrice weekly for 6 weeks and daily oral 0.5% CMC-Na solution, and two ivabradine + TAA groups, where two doses of ivabradine were tested. Low (10 mg/kg) and high (20 mg/kg) doses of ivabradine were orally given once daily to each group for 6 weeks concurrently with TAA injection. Results: TAA caused marked elevations in liver enzymes, increased MDA, depletion of antioxidant defenses, activation of NF-κB p65 and pro-inflammatory cytokines, dysregulation of apoptotic markers, and upregulation of the PI3K/AKT/mTOR and TGF-β pathways, accompanied by extensive collagen deposition. Ivabradine produced dose-dependent improvements in biochemical markers of liver function, restored oxidant/antioxidant balance, suppressed NF-κB p65/TNF-α, normalized Bax/Bcl-2/caspase-3 expression, and inhibited PI3K/AKT/mTOR as well as TGF-β signaling, leading to significant attenuation of fibrosis. Conclusions: The current findings indicate that ivabradine exerts potent antioxidant, anti-inflammatory, anti-apoptotic, and antifibrotic actions against TAA-induced hepatic fibrosis. Future clinical studies are recommended to determine whether these protective effects translate to patients with chronic liver disease. Full article

Background: Epstein–Barr virus (EBV) infection is common in childhood and frequently accompanied by liver enzyme abnormalities. Although hepatic involvement is generally self-limited, pediatric data on predictors of hepatitis and biochemical recovery dynamics remain limited. This study aimed to evaluate the frequency and severity of hepatic involvement in children with primary EBV infection and identify clinical and laboratory features associated with hepatitis. Methods: This retrospective cohort study included children aged 0–18 years with serologically confirmed primary EBV infection at a tertiary center between January 2015 and November 2024. Patients with cytomegalovirus co-infection, hepatotropic viral infections, chronic liver disease, hepatotoxic drug exposure, or incomplete records were excluded. Demographic, clinical, and laboratory data were collected. Hepatic involvement was defined as ALT elevation above age-adjusted upper limits. Group comparisons utilized appropriate parametric and non-parametric tests, and logistic regression assessed predictors of hepatitis. Results: A total of 294 patients were included (median age: 6.1 years), of whom 48.6% were male. Hepatitis occurred in 59.2% of cases. Children with hepatitis were older than those without (median 6.7 vs. 5.3 years, p < 0.001). Logistic regression demonstrated that increasing age independently predicted hepatitis (odds ratio per year increase: 1.010; 95%CI 1.005–1.015; p < 0.001). Median time to ALT normalization was 20 days, and no patient developed acute liver failure. Conclusions: Hepatic involvement is common in pediatric EBV infection and is more frequent in older children. Despite significant biochemical abnormalities, all patients recovered fully with supportive care. Recognizing age-related risk and typical recovery patterns may reduce unnecessary investigations and guide appropriate management in pediatric EBV hepatitis. Full article

Thrombocytopenia affects up to 10% of pregnant women and represents the second most common blood disorder during pregnancy. Its causes include immune-mediated thrombocytopenia, hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, preeclampsia (PE), and benign pregnant thrombocytopenia. Diagnosis is crucial because the cause dictates the effect on maternal health, pregnancy management, and neonatal outcomes. This narrative review examines the range of thrombocytopenia during pregnancy, primarily focusing on diagnostic evaluation, underlying pathophysiological causes, and differential diagnosis. In addition, it organizes maternal and fetal complications that might be caused by the condition, such as bleeding, preterm birth, and neonatal thrombocytopenia. Moreover, current patient management based on available evidence and clinical practice is discussed, including immunomodulatory therapies, platelet transfusions, clinical monitoring, and supportive care. A thorough and clinically guided approach to thrombocytopenia in pregnancy is indispensable for maximizing maternal and fetal outcomes and facilitating the personalization of perinatal care. Full article

Boron compounds, classified as prohibited food additives due to their high toxicity, persist in pesticides and fertilisers, industrial processes, food supply chains, and consumer goods, perpetuating multisource exposure risks. Chronic ingestion may induce fatal hepatorenal injury; however, mechanistic insights and epidemiological surveillance remain critically lacking amidst sector-wide regulatory gaps. This study employed integrated cellular and organismal models to elucidate the relationship between boron-induced hepatotoxicity and ferroptosis. We demonstrate that dietary boron accumulation in chicken livers is associated with histopathological damage, mitochondrial cristae dissolution and atrophy (a hallmark of ferroptosis), and elevated serum biomarkers AST and ALT. Boron exacerbates oxidative damage in hepatocytes by elevating malondialdehyde (MDA) production while modulating the Nrf2/ARE antioxidant signaling pathway—specifically downregulating key genes (Nrf2, HO-1, GCLM, CAT). Concurrently, it inhibits critical antioxidant enzymes (SOD, T-AOC), thereby depleting cellular antioxidant defenses. Crucially, boron disrupts iron homeostasis and induces ferroptosis by dysregulating the SLC7A11-GPX4 pathway: upregulating pro-ferroptotic genes (ACSL4, TF, TFR) and downregulating cytoprotective genes (SLC7A11, GPX4, FTH1). Co-treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) attenuated boron-induced oxidative damage, whereas the ferroptosis inducer Erastin potentiated toxicity. Collectively, we pioneer the dual-pathogenic mechanism of boron hepatotoxicity—oxidative stress and ferroptotic cell death—establishing the SLC7A11/GPX4 axis as a novel therapeutic target against boron toxicity. Full article

Background/Objectives: Systemic levels of the adipokine adiponectin are elevated in chronic liver disease including primary sclerosing cholangitis (PSC). Inflammatory bowel disease (IBD) and PSC are closely associated diseases, but in IBD serum adiponectin levels are near normal. Urinary and fecal biomarkers have been suggested to be superior to the corresponding serum protein for disease diagnosis, but urinary and fecal adiponectin have not been analyzed in PSC. The aim of this study was to evaluate the adiponectin in human serum, urine, and feces as a potential diagnostic tool for PSC. Methods: Serum and urine samples were collected from 74 IBD patients, 40 PSC patients (35 patients with PSC and IBD (16 patients for urine) and 5 patients with PSC without underlying IBD), and 17 controls. Feces samples from 53 IBD patients and 11 PSC patients (8 of them with PSC-IBD) were available for this study. Adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Results: Urinary and serum adiponectin levels in IBD patients and controls were comparable. Urinary, fecal and serum adiponectin in patients with ulcerative colitis and Crohn’s disease were similar and did not change, even with higher fecal calprotectin, a marker of intestinal inflammation in IBD. The three IBD patients with a high Gastrointestinal Symptom Rating Scale score as a marker for clinical activity had highly elevated urinary adiponectin. Systemic adiponectin levels were significantly elevated in the PSC-IBD cohort relative to the IBD-only group, suggesting its potential utility in clinical screening. Urinary and fecal adiponectin levels were similar between the cohorts. In PSC/PSC-IBD, serum adiponectin did not increase with higher fibrosis scores. Serum, urine, and fecal adiponectin were not correlated in both patient cohorts, except for a negative association of fecal and urine adiponectin in PSC. Conclusions: This exploratory study revealed preliminary findings suggesting an association between urinary adiponectin and severe gastrointestinal symptoms in IBD. In PSC-IBD, serum adiponectin is higher compared to IBD patients and continuous measurement may be used for PSC-IBD screening. Full article

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel, and its activator, the alcohol breakdown product acetaldehyde, plays a key role in the pathomechanism of alcoholic liver disease (ALD). We hypothesized that TRPA1 is expressed in the liver, can be activated by alcohol breakdown products, and plays a role in ALD. We aimed (1) to confirm the presence of TRPA1 in liver samples from C57BL6/J mice by RNAscope in situ hybridization combined with immunostaining, (2) to prove that alcohol breakdown products may activate human TRPA1 by calcium-imaging, and (3) to investigate the role of TRPA1 in a chronic continuous 20% alcohol drinking model involving Trpa1 gene-deficient (KO) mice. The liver enzyme levels were evaluated; moreover, the steatosis, portal and interface inflammatory infiltrations were assessed in PAS–hematoxylin-stained sections. We detected Trpa1 expression in both hepatocytes and liver macrophages. We observed elevated liver enzyme levels in wild-type mice. Significant inflammatory infiltration and steatosis developed in both WT and KO mice in response to alcohol; however, no significant differences were found between the genotypes. We conclude that Trpa1 is expressed in hepatocytes and liver macrophages; however, the chronic alcohol-induced steatosis and inflammatory infiltration develop through a TRPA1-independent mechanism. Full article

Crimean–Congo Hemorrhagic Fever (CCHF) disease, caused by the CCHF virus (CCHFV), poses a significant fatality risk whose underlying pathological mechanisms, including the contribution of coagulation factors, imbalances and platelet abnormalities, remain poorly understood. Here we present a meta-analysis and meta-regression analysis using clinical data from coagulation assays and platelet parameters as predictive disease indices with the goal of uncovering pathognomonic factors and to pave a way for the development of effective therapeutic approaches. Methods: We systematically analyzed published studies reporting coagulation assays and platelet indices in patients with confirmed CCHF. Data from 1779 patients across the published studies were analyzed to assess associations between laboratory parameters and the fatality risk, while evaluating heterogeneity and prognostic significance. Results: Fatal outcomes were strongly associated with elevated liver enzymes (AST: 1116.71 ± 1454.08 IU/mL; ALT: 446.56 ± 457.41 IU/mL) and prolonged clotting times (PT: 19.53 ± 6.57 s; aPTT: 64.02 ± 23.13 s; INR: 1.53 ± 0.56). D-dimer levels did not significantly predict fatality. Thrombocytopenia and coagulopathy emerged as independent risk factors for adverse outcomes. Notably, protein C and protein S levels did not differ between survivors and non-survivors, suggesting that the coagulopathy is not purely consumptive or a result of impaired hepatic synthesis. In contrast, mildly reduced antithrombin levels (83.65 ± 19.90) were weighted toward increased mortality. Full article

In this study, we evaluated the physiological effects of fermented metabolites derived from puffed grains (z), fermented using Bacillus amyloliquefaciens NPKE6, a strain isolated from Korean water kimchi. In vitro assays showed that NPKE6-FM significantly increased antioxidant enzyme activities (SOD, CAT, GPx) and digestive enzyme activities (α-amylase, protease), suggesting its strong biofunctional potential. To confirm its in vivo efficacy, we established two inflammatory disease models—ulcerative colitis and liver injury—in male C57BL/6 mice. Colitis was induced by oral administration of 1% dextran sodium sulfate (DSS, 1 mL), while liver injury was induced by intraperitoneal injection of acetaminophen (APAP, 300 mg/kg) three times per week for 4 weeks. In disease-induced control groups, elevated serum biomarkers (AST, ALT, ALP) and reduced antioxidant activity were observed. Experimental groups received 10 or 50 mg/kg/day of NPKE6-FM for 4 weeks. Treatment significantly restored antioxidant enzyme levels and reduced inflammatory markers such as TNF-α and IL-6. In the colitis model, NPKE6-FM alleviated DSS-induced tissue damage, evidenced by improved colon length, weight, and histological scores. Gene expression analysis showed downregulation of iNOS and COX-2 in colon tissues and Akt and MCP-1 in liver, indicating molecular anti-inflammatory effects. Although liver histopathology did not show marked improvement, biochemical and gene expression results supported its protective role. In summary, NPKE6-FM demonstrated potent antioxidant and anti-inflammatory activities in vitro and in vivo, indicating its potential as a functional food additive to prevent or alleviate inflammatory conditions such as colitis and liver injury. Full article

Background: Immune-mediated cholangitis (IMC) is a rare complication of immune checkpoint inhibitor (ICI) therapy, and its clinical characteristics and prognostic implications remain unclear. This study aimed to clarify the characteristics, risk factors, and outcomes of IMC compared with non-cholangitis cases of immune-mediated hepatotoxicity (IMH). Methods: In this single-center retrospective study, 1332 patients who received ICIs between 2014 and 2023 were analyzed. IMH was diagnosed based on liver enzyme elevation and exclusion of other liver diseases, while IMC was identified through characteristic imaging findings. Baseline factors, clinical presentations, treatment responses, and overall survival (OS) were evaluated. Multivariate analysis identified IMC risk and IMH prognostic factors. Results: Among the cohort, 81 (6.1%) patients had IMH, including 10 (0.8%) with IMC. Baseline eosinophil count > 270/μL (odds ratio [OR] 10.33, p = 0.004) and C-reactive protein (CRP) levels > 0.8 mg/dL (OR 6.260, p = 0.027) were independent predictors of IMC. IMC was associated with delayed onset, cholestatic liver injury, abdominal pain, and neutrophil-predominant inflammation. In prognostic analysis, IMC was not associated with OS. However, cholestatic liver injury (hazard ratio [HR] 2.318, p = 0.023) and neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 (HR 3.622, p = 0.001) were independent predictors of poor OS. Bile duct imaging abnormalities before or after onset were common in patients with treatment-resistant IMC. Conclusions: Baseline eosinophil count and CRP may help predict IMC. While IMC was not a prognostic factor, cholestatic injury and high NLR were associated with worse outcomes. IMC exhibits distinct clinical features, and radiologic findings may support earlier diagnosis and management. Full article