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11 pages, 427 KB  
Article
Hyperbilirubinemia After Redo Valve Surgery: Incidence, Perioperative Risk Factors, and Association with Early Clinical Outcomes
by Can Zhao, Wei Yao, Jianping Xu, Guangyu Pan and Shen Liu
J. Cardiovasc. Dev. Dis. 2026, 13(6), 268; https://doi.org/10.3390/jcdd13060268 (registering DOI) - 15 Jun 2026
Abstract
Background: Postoperative hyperbilirubinemia is a serious complication after cardiac surgery and has been associated with increased perioperative morbidity and mortality. However, data specifically addressing patients undergoing redo valve surgery remain limited. This study aimed to determine the incidence and risk factors of postoperative [...] Read more.
Background: Postoperative hyperbilirubinemia is a serious complication after cardiac surgery and has been associated with increased perioperative morbidity and mortality. However, data specifically addressing patients undergoing redo valve surgery remain limited. This study aimed to determine the incidence and risk factors of postoperative hyperbilirubinemia after redo valve surgery, and evaluate its association with early postoperative outcomes. Methods: We retrospectively reviewed 259 adult patients who underwent elective redo valve surgery under cardiopulmonary bypass (CPB) between March 2018 and July 2024. Postoperative hyperbilirubinemia was defined as a serum total bilirubin level > 3 mg/dL at any time after surgery. Patients were divided into a hyperbilirubinemia group and a non-hyperbilirubinemia group. Perioperative variables were compared between groups. Univariable and multivariable logistic regression analyses were performed to identify risk factors for postoperative hyperbilirubinemia. Postoperative complications and in-hospital mortality were also compared. Results: Postoperative hyperbilirubinemia occurred in 101 of 259 patients (39.0%). Compared with patients without hyperbilirubinemia, those with hyperbilirubinemia had longer mechanical ventilation and intensive care unit stay, and higher rates of pneumonia, reintubation, tracheostomy, continuous renal replacement therapy, and in-hospital mortality. Univariable logistic regression showed that higher EuroSCORE II, higher preoperative total bilirubin and direct bilirubin levels, lower hemoglobin and platelet count, pulmonary hypertension, anemia, longer operative time, CPB duration, and aortic cross-clamp time, lower nasopharyngeal temperature, greater intraoperative blood loss, larger red blood cell and plasma transfusion volumes, and concomitant surgery on all three valves were associated with postoperative hyperbilirubinemia. Multivariable analysis identified elevated preoperative direct bilirubin, prolonged CPB duration, and more plasma transfusion as independent risk factors. Receiver operating characteristic analysis showed that peak postoperative total bilirubin had moderate prognostic discrimination for in-hospital mortality, with an optimal cut-off value of 3.95 mg/dL (AUC 0.756, sensitivity 66.7%, specificity 80.2%, p = 0.003). Conclusions: Postoperative hyperbilirubinemia is common after redo valve surgery and is associated with worse early postoperative outcomes and higher in-hospital mortality. In this setting, postoperative bilirubin elevation should be interpreted primarily as a prognostic marker of perioperative stress and hepatic vulnerability rather than a direct causal driver of adverse outcomes. Elevated preoperative direct bilirubin, prolonged CPB duration, and greater plasma transfusion were independently associated with the development of postoperative hyperbilirubinemia in this high-risk population. Full article
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10 pages, 1190 KB  
Article
Single-Center Retrospective Study of Hospitalized Hepatitis A Cases in Southern Bulgaria, 2015–2023
by Meri Hristamyan, Simona Zlatanova, Vanya Rangelova and Ilia Tsachev
Healthcare 2026, 14(10), 1428; https://doi.org/10.3390/healthcare14101428 - 21 May 2026
Viewed by 287
Abstract
Background/Objectives: The hepatitis A virus (HAV) infection continues to represent a considerable public health issue in Eastern Europe, particularly in Bulgaria, where incidence rates exceed the EU average. This study sought to investigate the epidemiological and clinical aspects of acute hepatitis A in [...] Read more.
Background/Objectives: The hepatitis A virus (HAV) infection continues to represent a considerable public health issue in Eastern Europe, particularly in Bulgaria, where incidence rates exceed the EU average. This study sought to investigate the epidemiological and clinical aspects of acute hepatitis A in Southern Bulgaria between 2015 and 2023 and to assess changes during the COVID-19 pandemic period. Methods: A retrospective descriptive-analytic study was conducted among 1810 hospitalized patients with confirmed acute HAV infection at a tertiary infectious diseases center from 2015 to 2023. Demographic, clinical, laboratory, and temporal data were analyzed, comparing the pre-pandemic period (2015–2019) with the pandemic phase (2020–2023). Results: Most hospitalized cases occurred during the pre-pandemic period (88.0%), with epidemic peaks observed in 2016–2017. Individuals under 18 years comprised 69.9% of cases, with a median age of 9 years and a slight male predominance of 54.9%. A notable seasonal pattern was identified, characterized by peaks in autumn and early winter. Patients hospitalized during the pandemic period were significantly older compared with the pre-pandemic period (median age 14 vs. 8 years, p < 0.001). Adults experienced significantly longer hospitalization and higher ALT, AST, total bilirubin, and direct bilirubin levels compared with pediatric patients (all p < 0.001). The median duration of hospitalization was 7 days (IQR 6–10). Two in-hospital deaths were recorded, corresponding to a case fatality rate of 0.11%. Conclusions: Hepatitis A in Southern Bulgaria mostly impacts children but exhibits changing epidemiological trends, underscoring the necessity for focused preventative methods, such as vaccination and enhanced surveillance. Full article
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29 pages, 9213 KB  
Article
Hepato-Protective Effect of Pomegranate and Persimmon Juices Against Oxidative Stress and Inflammation in Cyclosporine-Induced Cholestasis in Rats
by Rasha S. Mohamed and Karem Fouda
Foods 2026, 15(9), 1473; https://doi.org/10.3390/foods15091473 - 23 Apr 2026
Viewed by 532
Abstract
Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated [...] Read more.
Background: Oxidative liver damage, fibrosis, cirrhosis and liver failure are caused by reactive oxygen species and inflammatory responses triggered by bile retention during prolonged cholestasis. Pomegranate and persimmon fruits, which are loaded with bioactive compounds that have anti-inflammatory and antioxidant properties, were evaluated separately for their efficacy in preventing oxidative stress and inflammation in cholestasis. Methods: Pomegranate and persimmon juices were analyzed for their vitamin C, carotenoids and organic acid levels, phenolic profile, and antioxidant activity. Liver protection against oxidative stress and inflammation brought on by cyclosporine-induced cholestasis in rats was verified by biochemical measurements, metabolite identification, and histopathologic examination. To forecast the mechanism of pomegranate and persimmon anti-inflammatory action, an in silico assessment was also carried out. Results: Vitamin C levels in pomegranate and persimmon juices were 99.55 and 51.75 µg/g, respectively. In both pomegranate and persimmon juices, gallic acid was the most prevalent phenolic compound (123.20 and 50.69 µg/g, respectively). Pomegranate and persimmon juices significantly (p < 0.05) reduced the rise in liver values of MDA, NO, TNF-α, IL-6, IL-1β, and TLR4, as well as serum values of total and direct bilirubin caused by cyclosporine. Additionally, the alteration of metabolites, particularly amino acids, demonstrated the inhibitory effect of pomegranate and persimmon juices on liver damage. Gallic acid’s and catechin’s substantial binding affinities with target inflammatory cytokines (TNF-α and TLR4) were further validated by molecular docking. Conclusions: These results showed that pomegranate and persimmon juices mainly modulated inflammation and oxidative stress to provide hepato-protective benefits against cyclosporine-induced cholestatic liver injury. Full article
(This article belongs to the Section Food Nutrition)
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17 pages, 1890 KB  
Article
Paired In-Hospital Dynamics in Hepatitis E: Rapid Transaminase Decline and Persistent Hyperbilirubinemia in a Romanian Cohort
by Florentina Dumitrescu, Eugenia-Andreea Marcu, Vlad Pădureanu, Virginia Maria Rădulescu and Ion Rogoveanu
Diagnostics 2026, 16(7), 1012; https://doi.org/10.3390/diagnostics16071012 - 27 Mar 2026
Viewed by 552
Abstract
Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients [...] Read more.
Background/Objectives: Hepatitis E virus (HEV) infection is an increasingly recognized cause of acute hepatitis in Europe, but short-term in-hospital laboratory dynamics remain insufficiently described in hospitalized cohorts. We aimed to characterize admission biochemical abnormalities and paired admission-to-discharge laboratory changes in hospitalized patients with acute hepatitis E from Craiova, Romania, with exploratory sex- and age-stratified analyses. Methods: We conducted a single-center retrospective observational study including 40 consecutive hospitalized patients with acute hepatitis E during 2024–2025. Admission and discharge laboratory values were compared at the within-patient level, and exploratory subgroup analyses by sex and age class were performed. Given the limited sample size, multivariable analyses were restricted to parsimonious age-adjusted models for selected endpoints. Results: The cohort comprised 22 females (55%) and 18 males (45%), with a mean age of 53.05 ± 21.44 years; two in-hospital deaths occurred. At admission, marked transaminase elevation and frequent hyperbilirubinemia were observed, with 70% of patients having total bilirubin ≥ 2 mg/dL and 40% ≥ 10 mg/dL. During hospitalization, ALT and AST declined markedly, whereas total and direct bilirubin improved more modestly, indicating slower resolution of jaundice/cholestatic abnormalities. Platelets increased, while prothrombin index changes were heterogeneous. Male patients had higher bilirubin values at admission and discharge and more frequent clinically relevant hyperbilirubinemia thresholds; however, these findings should be interpreted cautiously given the small sample size, the retrospective design, and the absence of standardized clinical confounders and mechanistic data. Exploratory age-stratified analyses did not identify robust differences after multiplicity control. Conclusions: In hospitalized hepatitis E, hepatocellular injury markers improved rapidly during hospitalization, whereas cholestatic abnormalities resolved more slowly and often remained clinically relevant at discharge. The observed sex-related cholestatic pattern should be considered exploratory and requires confirmation in larger studies with standardized clinical covariates and longer follow-up. These findings support closer monitoring of bilirubin trajectories at discharge, particularly in male patients, and highlight the need for integrating laboratory dynamics into short-term clinical assessment of hospitalized HEV cases. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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7 pages, 1939 KB  
Case Report
An Unusual Presentation of Cholangiocarcinoma: The Sister Mary Joseph Nodule—A Case Report
by Toni Esposito, Niharika Singh, Riddhish Sheth and George Keckeisen
Reports 2026, 9(1), 51; https://doi.org/10.3390/reports9010051 - 3 Feb 2026
Viewed by 679
Abstract
Background and Clinical Significance: Sister Mary Joseph nodules (SMJN) are rare extra-intestinal manifestations of metastatic intra-abdominal and pelvic malignancies, often indicating advanced disease and poor prognosis. Their association with cholangiocarcinoma (CCA) is particularly uncommon, with only a limited number of reported cases. [...] Read more.
Background and Clinical Significance: Sister Mary Joseph nodules (SMJN) are rare extra-intestinal manifestations of metastatic intra-abdominal and pelvic malignancies, often indicating advanced disease and poor prognosis. Their association with cholangiocarcinoma (CCA) is particularly uncommon, with only a limited number of reported cases. Case Presentation: We present a case report of a 65-year-old previously healthy male who presented for an elective umbilical hernia repair. Additional findings of elevated direct bilirubin and a history of fatigue in the patient prompted further evaluation with biopsy and imaging, which revealed advanced-stage intrahepatic CCA. Following the diagnosis, the patient underwent biliary stenting and chemotherapy. Conclusions: The variable presentation of SMJN, along with its frequent misdiagnosis, often delays recogni-tion and management of the underlying malignancy. This case of SMJN in the setting of CCA highlights the complex interplay between intra-abdominal and pelvic malignancies and their impact on different organ systems. With the rising incidence and mortality rates associated with CCA, early recognition is essential to improving patient outcomes. This underscores the need for increased clinical awareness and further research, thus support-ing the development of this case report. Full article
(This article belongs to the Section Oncology)
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16 pages, 2645 KB  
Article
Point-of-Care Bilirubin Testing in Neonates: Comparative Performance of Blood Gas Analysis and Transcutaneous Bilirubinometry
by Andrew Xu, Bincy Francis, Kay Weng Choy, George Francis Dargaville, Amy Surkitt, David Tran, Rami Subhi and Wei Qi Fan
Healthcare 2026, 14(3), 370; https://doi.org/10.3390/healthcare14030370 - 1 Feb 2026
Viewed by 1088
Abstract
Background: Neonatal jaundice is a common condition with potentially severe complications such as bilirubin-induced neurological dysfunction and kernicterus. While serum bilirubin (SBR) remains the standard laboratory measurement, point-of-care methods, such as transcutaneous bilirubinometry (TcB) and blood gas analysers (BGAs), offer rapid, less [...] Read more.
Background: Neonatal jaundice is a common condition with potentially severe complications such as bilirubin-induced neurological dysfunction and kernicterus. While serum bilirubin (SBR) remains the standard laboratory measurement, point-of-care methods, such as transcutaneous bilirubinometry (TcB) and blood gas analysers (BGAs), offer rapid, less invasive alternatives. Direct comparisons of their diagnostic accuracy remain limited. Objective: The aim of this study was to assess and compare diagnostic accuracy and clinical utility of TcB and BGA against SBR in neonatal hyperbilirubinaemia screening. Methods: This retrospective study included neonates (n = 221) with concurrent SBR, BGA, and TcB measurements (n = 333). Assessment was via Passing–Bablok regression, Bland–Altman analysis, and Spearman correlation. Diagnostic performance was evaluated against jaundice thresholds in phototherapy charts (≥95th percentile threshold). Subgroup analyses considered phototherapy status, haemoglobin concentration, and Fitzpatrick skin type. Results: BGA showed stronger agreement with SBR (R2 = 0.88) than TcB (R2 = 0.43). BGA remained accurate regardless of phototherapy or haemoglobin levels. TcB accuracy declined post-phototherapy with reduced predictive value in darker-skinned neonates (Fitzpatrick III–VI) and increased false discovery rates. Both methods demonstrated low sensitivity (45.8%) but high specificity (>95%) and negative predictive value (~91%) for clinically significant hyperbilirubinaemia. BGA had a higher diagnostic odds ratio (47.5) than TcB (19.3). When individual patient sequential SBR and BGA measurements were compared for jaundice tracking (n = 175), there was high correlation, (r = 0.971) with no statistical differences, and 50% of measurements achieving agreement within 10 μmol/L. Conclusions: BGA is a more reliable alternative to SBR than TcB, particularly in time-critical or resource-limited settings. While TcB remains a non-invasive screening tool, limited accuracy post-phototherapy and with darker skinned neonates indicate confirmatory SBR testing. These findings support the selective and context-aware use of BGA and TcB to optimise neonatal hyperbilirubinaemia management and reduce interventions. Full article
(This article belongs to the Section Clinical Care)
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13 pages, 1079 KB  
Article
Blood Biochemical Parameters in Non-Native Armored Catfishes (Loricariidae) from Highland Rivers of Central Vietnam
by Tran Duc Dien, Ekaterina V. Ganzha and Efim D. Pavlov
Hydrobiology 2026, 5(1), 5; https://doi.org/10.3390/hydrobiology5010005 - 1 Feb 2026
Viewed by 794
Abstract
In the past decade, non-native suckermouth armored catfish, Pterygoplichthys spp., have spread throughout the highland rivers of Lam Dong province, Vietnam. We examined spatial and temporal variation in endocrine and biochemical profiles across different river reaches, river systems, and between two sampling years [...] Read more.
In the past decade, non-native suckermouth armored catfish, Pterygoplichthys spp., have spread throughout the highland rivers of Lam Dong province, Vietnam. We examined spatial and temporal variation in endocrine and biochemical profiles across different river reaches, river systems, and between two sampling years (2020 and 2022). Seven blood parameters related to metabolism and energy balance were measured: total and free triiodothyronine, cholesterol, triglycerides, total protein, creatinine, and direct bilirubin. Concentrations of thyroid hormones and cholesterol did not differ significantly across sites or years. Multivariate analyses indicated that thyroid-related pathways were only weakly influenced by the environmental variation, suggesting preserved thyroid homeostasis. In contrast, triglycerides, total protein, creatinine, and direct bilirubin varied among rivers and between years at the same site, likely reflecting differences in food availability and energy balance. These results suggest that biochemical variation in non-native armored catfish is primarily expressed through lipid metabolism and protein turnover, while thyroid function remains comparatively conserved across invaded river habitats. Full article
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15 pages, 1079 KB  
Article
Three-Dimensional Models in Hepatic Surgery: Clinical Outcomes A Single-Center Experience
by María Victoria Vieiro Medina, Laura Alonso Murillo, Carlos Ernesto García Vasquez, Marta de la Fuente Bartolomé, Victor Nieto Barros, Fernando Neria and Santos Jiménez de los Galanes Marchán
J. Clin. Med. 2025, 14(24), 8659; https://doi.org/10.3390/jcm14248659 - 6 Dec 2025
Cited by 2 | Viewed by 780
Abstract
Background: Hepatic resection requires precise knowledge of vascular anatomy and remnant liver volume to guarantee both safety and efficacy. Three-dimensional (3D) models, either virtual or printed, have been proposed as tools to optimize surgical planning, education, and intraoperative navigation. Material and Methods: This [...] Read more.
Background: Hepatic resection requires precise knowledge of vascular anatomy and remnant liver volume to guarantee both safety and efficacy. Three-dimensional (3D) models, either virtual or printed, have been proposed as tools to optimize surgical planning, education, and intraoperative navigation. Material and Methods: This retrospective observational study evaluated the impact of 3D model utilization (virtual and printed), in 89 patients who underwent elective hepatectomy at Infanta Elena University Hospital (Valdemoro, Madrid, Spain) between May 2018 and May 2023. The implementation of 3D modeling began to be routinely implemented as of November 2020. Patients were divided into two groups: those without 3D modeling (n = 40) and those with 3D modeling (n = 49). Results: Baseline characteristics were comparable between groups. Intraoperative blood loss was significantly lower in the 3D model group (median 175 mL vs. 262.5 mL; p < 0.001), with no statistically significant differences in operative time, complication rate (Clavien–Dindo classification), length of hospital stay, or in-hospital mortality. Multivariable analysis identified dyslipidemia, postoperative sodium delta, and postoperative increase in direct bilirubin as independent risk factors for complications, whereas albumin demonstrated a protective effect. Conclusions: Three-dimensional modeling improves anatomic orientation and reduces intraoperative blood loss, although it does not significantly modify classic perioperative outcomes. Its principal value appears to reside in preoperative planning and technical safety rather than direct clinical impact. Full article
(This article belongs to the Section General Surgery)
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24 pages, 5310 KB  
Article
Evaluation of Hematological, Biochemical, and Coagulation Tests in Patients with Hepatitis C
by Ieva Janulaityte, Gintare Petkute, Asta Maciuliene, Jurgita Borodiciene, Jokubas Kareiva and Astra Vitkauskiene
Medicina 2025, 61(11), 2049; https://doi.org/10.3390/medicina61112049 - 17 Nov 2025
Viewed by 1094
Abstract
Background and Objectives: Hepatitis C virus (HCV) remains a significant cause of chronic liver disease worldwide. While direct-acting antivirals achieve high cure rates, the interplay between viral load, gender, and routine laboratory parameters remains unclear. This study aimed to investigate hematological, biochemical, [...] Read more.
Background and Objectives: Hepatitis C virus (HCV) remains a significant cause of chronic liver disease worldwide. While direct-acting antivirals achieve high cure rates, the interplay between viral load, gender, and routine laboratory parameters remains unclear. This study aimed to investigate hematological, biochemical, and coagulation profiles, as well as derived non-invasive indices, in HCV-infected patients, stratified by gender and viremia levels. Materials and Methods: This retrospective study included 367 patients with HCV infection (223 males and 144 females). Patients were divided into four groups: high viremia males (hiVM), high viremia females (hiVF), low viremia males (loVM), and low viremia females (loVF), using 800,000 IU/mL as the threshold. Routine hematological, biochemical, and coagulation tests were conducted, and derived indices (FIB-4, APRI, AST/ALT ratio, PLR, NLR, SII, AISI, PNI, HALP, PAR, NAR) were calculated. Results: Significant gender- and viremia-specific differences were observed. hiVM showed higher erythrocyte indices and altered coagulation parameters, whereas hiVF had increased lymphocyte counts and AST/ALT ratio elevation. loVM displayed reduced hemoglobin and hematocrit, along with worse coagulation results. Biochemical analysis revealed gender differences in GGT, bilirubin, and albumin levels. Among derived indices, FIB-4 and APRI were higher in loVM, while SII and PLR were elevated in loVF. At the second visit after 17±4 weeks, when patients had no detectable HCV DNA in the peripheral blood, most indices improved significantly across groups. Conclusions: HCV infection affects laboratory profiles depending on gender and viremia levels. Non-invasive indices from routine tests offer valuable insights into inflammatory and nutritional status. Using these indices alongside traditional markers may aid hypothesis generation or clinical assessment and help prioritize further assessment for HCV patients. Full article
(This article belongs to the Topic Human Anatomy and Pathophysiology, 3rd Edition)
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11 pages, 1435 KB  
Article
SGLT2 Inhibitors Are Associated with Left Ventricular Reverse Remodeling in Patients with Non-Compaction Cardiomyopathy—A Prospective Observational Cohort Trial
by Andraž Cerar, Gregor Poglajen, Gregor Zemljič, Sabina Frljak, Neža Žorž, Martina Jaklič, Renata Okrajšek, Miran Šebeštjen and Bojan Vrtovec
Biomedicines 2025, 13(11), 2773; https://doi.org/10.3390/biomedicines13112773 - 13 Nov 2025
Viewed by 1250
Abstract
Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. Methods: Thirty consecutive [...] Read more.
Background/Objectives: Sodium glucose co-transporter 2 inhibitors (SGLT2is) improve outcomes in heart failure; however, data in left ventricular non-compaction cardiomyopathy (LVNC) patients are limited. We sought to analyze the clinical effects of the SGLT2is dapagliflozin and empagliflozin in patients with LVNC. Methods: Thirty consecutive LVNC patients diagnosed by CMR were prospectively enrolled. Clinical, biochemical and echocardiography data were obtained at the initiation of the SGLT2is and at the 12-month follow-up. All patients were on stable guideline-directed medical therapy. A response to SGLT2i therapy was defined as an improvement in LVEF ≥ 5% at 12 months. Results: Of the 30 enrolled patients, 25 were male, with a mean age of 49 ± 16 years and few comorbidities. Dapagliflozin 10 mg was prescribed to 23 patients and empagliflozin 10 mg to 7 patients. Five patients experiened an adverse event during follow-up (one sudden cardiac death; four heart transplantations or LVAD implantations). During follow-up, significant improvements were observed in LVEF (32.1 ± 6.9% vs. 43.5 ± 9.7%; p = 0.003), LVOT VTI (14.8 ± 6.5 cm vs. 17.6 ± 3.3 cm; p = 0.008), E/e′ (14.8 ± 4.7 vs. 10.0 ± 4.1; p < 0.001), and TAPSE (2.0 ± 0.4 cm vs. 2.3 ± 0.4 cm; p = 0.012). NT-proBNP levels decreased significantly (2025 ± 2198 pg/mL vs. 582 ± 803 pg/mL; p = 0.005). Eighteen patients responded favorably to SGLT2i therapy (Group A), whereas seven showed no significant LVEF improvement (Group B). The groups did not differ significantly in age, sex, baseline creatinine, or bilirubin. Compared to Group B, Group A had a smaller baseline LV end-diastolic diameter (6.3 ± 0.8 cm vs. 7.1 ± 0.9 cm; p = 0.025) and lower NT-proBNP levels (1720 ± 1662 pg/mL vs. 4527 ± 4397 pg/mL; p = 0.02). Conclusions: In patients with LVNC, SGLT2i therapy is associated with significant reverse remodeling and functional improvement. Benefits may be greater in those with less advanced disease. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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12 pages, 752 KB  
Review
Bilirubin Photoisomers in Neonatal Jaundice
by Dennis Lindqvist, Magnus Hansson, Mercy Thomas, Christian V. Hulzebos, Libor Vitek, Andries Blokzijl and Miranda van Berkel
Int. J. Mol. Sci. 2025, 26(21), 10791; https://doi.org/10.3390/ijms262110791 - 6 Nov 2025
Viewed by 2826
Abstract
Phototherapy is the standard treatment for neonatal hyperbilirubinemia. During phototherapy, the highly lipophilic bilirubin is converted into more hydrophilic photoisomers, which can be more easily excreted from the body. This process typically lowers bilirubin levels to non-harmful concentrations. However, despite decades of research [...] Read more.
Phototherapy is the standard treatment for neonatal hyperbilirubinemia. During phototherapy, the highly lipophilic bilirubin is converted into more hydrophilic photoisomers, which can be more easily excreted from the body. This process typically lowers bilirubin levels to non-harmful concentrations. However, despite decades of research into the formation and role of bilirubin photoisomers, methodological limitations and the compound’s complex biochemistry have hindered comprehensive understanding. This review provides an updated overview of current knowledge on bilirubin photoisomers, including their basic chemistry, analytical quantification, clinical relevance, and future research directions. Improved insight into the mechanism of photoisomer formation and kinetics may inform optimization of phototherapy parameters, including light intensity and wavelength, and offer additional indicators of treatment efficacy beyond total bilirubin concentration. Advances in sensitive and standardized mass spectrometry techniques now enable more accurate measurement of different bilirubin isomers and serve as a first step towards a deeper insight into the clinical relevance of photoisomers. Full article
(This article belongs to the Special Issue Bilirubin: Health Challenges and Opportunities)
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27 pages, 5615 KB  
Article
Uncovering Exposure Patterns of Metals, PFAS, Phthalates, and PAHs and Their Combined Effect on Liver Injury Markers
by Doreen Jehu-Appiah and Emmanuel Obeng-Gyasi
J. Xenobiot. 2025, 15(6), 178; https://doi.org/10.3390/jox15060178 - 1 Nov 2025
Cited by 4 | Viewed by 2269
Abstract
People are exposed to mixtures of metals, per- and polyfluoroalkyl substances (PFAS), phthalates, and polycyclic aromatic hydrocarbons (PAH) rather than single chemicals, yet mixture inference is hampered by high dimensionality, correlation, missingness, and left-censoring below limits of detection (LOD). We analyzed 2013–2014 National [...] Read more.
People are exposed to mixtures of metals, per- and polyfluoroalkyl substances (PFAS), phthalates, and polycyclic aromatic hydrocarbons (PAH) rather than single chemicals, yet mixture inference is hampered by high dimensionality, correlation, missingness, and left-censoring below limits of detection (LOD). We analyzed 2013–2014 National Health and Nutrition Examination Survey (NHANES) biomarkers (n = 4367) to (i) recover latent, interpretable co-exposure structures and (ii) quantify how these mixtures relate to liver health. To denoise and handle censoring, we applied Principal Component Pursuit with LOD adjustment (PCP-LOD), decomposing the exposure matrix into a non-negative low-rank component (population co-exposure profiles) and a sparse component (individual spikes), and then used Bayesian Kernel Machine Regression (BKMR) to estimate nonlinear and interactive associations with AST, ALT, GGT, ALP, total bilirubin, and the Fatty Liver Index (FLI), retaining analytes with ≥50% detection. PCP-LOD revealed coherent clusters (e.g., long-chain PFAS grouping; shared metal loadings), while the sparse layer highlighted episodic phthalate elevations. BKMR indicated outcome-specific mixture effects: PAHs and selected phthalates showed consistently positive associations with ALP, GGT, and FLI; PFAS (PFOS, PFNA, PFOA) exhibited modest associations with ALP and bilirubin; metals displayed mixed directions. A joint increase in the overall mixture from the 25th to 75th percentile corresponded to an upward shift in FLI and a smaller rise in ALT. This censoring-aware low-rank-plus-sparse framework coupled with flexible mixture modeling recovers actionable exposure architecture and reveals clinically relevant links to liver injury and steatosis, motivating longitudinal and mechanistic studies to strengthen causal interpretation. Full article
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17 pages, 1862 KB  
Article
Oxidative Stress and Cirrhosis Severity: A Retrospective Cohort Analysis of Predictive and Interactive Effects with Inflammation
by Vlad Pădureanu, Lidia Boldeanu, Denisa Floriana Vasilica Pîrșcoveanu, Dalia Dop, Ramona Cioboată, Anca Bobîrcă and Virginia Maria Rădulescu
Metabolites 2025, 15(11), 711; https://doi.org/10.3390/metabo15110711 - 30 Oct 2025
Cited by 1 | Viewed by 777
Abstract
Background/Objectives: Oxidative stress is a central mechanism in the pathogenesis of cirrhosis, yet its clinical significance relative to established predictors remains unclear. Methods: We conducted a retrospective cohort study of 90 patients with cirrhosis hospitalized between October 2024 and March 2025. Clinical data, [...] Read more.
Background/Objectives: Oxidative stress is a central mechanism in the pathogenesis of cirrhosis, yet its clinical significance relative to established predictors remains unclear. Methods: We conducted a retrospective cohort study of 90 patients with cirrhosis hospitalized between October 2024 and March 2025. Clinical data, biochemical parameters, systemic inflammatory indices, and oxidative stress markers [malondialdehyde (MDA), 8-epi-prostaglandin F2α (8-epi-PGF2α)] were assessed at admission. Statistical analyses included non-parametric group comparisons, Spearman correlations, logistic regression with interaction terms, ROC analysis with bootstrap confidence intervals, model calibration and discrimination metrics, reclassification indices (NRI, IDI), and decision curve analysis (DCA). Results: Patients with advanced encephalopathy (HE3) had significantly higher MDA levels compared with HE1 (123.4 [107.6–248.4] vs. 131.0 [66.9–301.1] ng/mL; p = 0.021), while 8-epi-PGF2α showed a non-significant but consistent trend. Both oxidative markers correlated with biochemical dysfunction (MDA with INR and albumin; 8-epi-PGF2α with direct bilirubin). ROC analyses demonstrated modest discriminative ability (AUC 0.55–0.60) compared with albumin (AUC 0.74–0.90) and INR (AUC 0.72–0.88). In regression models, albumin remained the strongest independent predictor, whereas oxidative markers did not retain significance. Interaction models suggested that oxidative stress exerted context-dependent effects, particularly in patients with elevated inflammatory indices. Incremental predictive value beyond age and albumin was minimal (ΔAUC ≤ 0.01; NRI + 2–4%). DCA confirmed no added clinical utility. Conclusions: Classical clinical markers, particularly albumin and INR, dominate predictive accuracy in cirrhosis. Oxidative stress markers lack independent predictive power but consistently associate with worsening encephalopathy and liver dysfunction, underscoring their biological relevance and suggesting their role is best understood in conjunction with systemic inflammation. Full article
(This article belongs to the Special Issue Metabolite Profiles in Inflammatory Diseases)
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15 pages, 1455 KB  
Article
First Human Biomonitoring Evidence of Strobilurin Fungicide Exposure in South China: Impact on Oxidative Stress and Liver Damage
by Bo Zhang, Shuai Feng, Yanxia Gao, Wenxi Xie, Yiyu Chen and Shiming Song
Toxics 2025, 13(11), 908; https://doi.org/10.3390/toxics13110908 - 23 Oct 2025
Viewed by 855
Abstract
Background: Strobilurin fungicides (SFs) are widely detected in the environment, but data on their occurrence in humans and potential health effects are scarce. Objective: This study aimed to characterize the exposure to SFs in a human population from South China and to investigate [...] Read more.
Background: Strobilurin fungicides (SFs) are widely detected in the environment, but data on their occurrence in humans and potential health effects are scarce. Objective: This study aimed to characterize the exposure to SFs in a human population from South China and to investigate their potential association with biomarkers of oxidative stress and liver damage. Methods: In a cross-sectional study, we analyzed serum samples from healthy participants and secondary nonalcoholic fatty liver disease (S-NAFLD) patients. Concentrations of SFs and oxidative stress biomarkers including 8-iso-prostaglandin-F2α (8-PGF), 11β-prostaglandin F2α (11-PGF), 15(R)-prostaglandin F2α (15-PGF), and 8-oxo-7,8-dihydro-20-deoxyguanosine (8-OHdG) were measured. Associations between SF exposure, liver function biomarkers, and S-NAFLD prevalence were assessed using multivariate regression models. A mediation analysis was conducted to explore the role of oxidative stress. Results: Azoxystrobin (AZ), fluoxastrobin (FLUO), and fenamidone (FE) were the predominant compounds, with median concentrations ranging from 0.016 to 0.042 ng/mL. Significant positive correlations were observed between all frequently detected SFs and oxidative stress biomarkers (p < 0.05). FE was associated with a modest, albeit statistically significant, prevalence of S-NAFLD. AZ and FE were also found to be statistically significantly associated with altered levels of direct bilirubin (DBIL, FDR-q < 0.05). The exploratory mediation analysis indicated a statistically significant indirect effect (17.1% to 31.2%), suggesting that lipid peroxidation biomarkers could serve as potential mediators between AZ exposure and DBIL levels. Conclusions: This study provides the first evidence of widespread SF exposure in a South Chinese population and reveals significant associations with oxidative stress and AZ exposure with liver function biomarkers (i.e., DBIL), with exploratory analyses suggesting a potential mediating role of oxidative stress in this relationship. However, the cross-sectional design precludes causal inference, and the modest effect sizes warrant cautious interpretation. These findings highlight the need for further longitudinal research to confirm the hepatotoxicity of SFs in humans. Full article
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Case Report
Isolated Phlegmon of the Round Ligament of the Liver: Clinical Decision-Making in the Context of Lemmel’s Syndrome—A Case Report
by Georgi Popivanov, Marina Konaktchieva, Roberto Cirocchi, Desislava Videva and Ventsislav Mutafchiyski
Reports 2025, 8(4), 192; https://doi.org/10.3390/reports8040192 - 29 Sep 2025
Viewed by 757
Abstract
Background and Clinical Significance: The pathology of the round ligament (RL) is rare and often remains in the shadow of common surgical emergencies. The preoperative diagnosis is challenging, leaving the surgeon perplexed as to whether and when to operate. The presented case [...] Read more.
Background and Clinical Significance: The pathology of the round ligament (RL) is rare and often remains in the shadow of common surgical emergencies. The preoperative diagnosis is challenging, leaving the surgeon perplexed as to whether and when to operate. The presented case deserves attention due to the difficult decision to operate based solely on the clinical picture, despite negative imaging diagnostic results. Case presentation: A 76-year-old woman was admitted to the Emergency Department with 6 h complaints of epigastric pain, nausea, and vomiting. She was afebrile with stable vital signs. The abdomen was slightly tender in the epigastrium, without rebound tenderness or guarding. The following blood variables were beyond the normal range: WBC—13.5 × 109/L; total bilirubin 26 mmol/L; amylase—594 U/L; CRP 11.4 mg/L; ASAT—158 U/L; and ALAT—95 U/L. The ultrasound (US) and multislice computed tomography (MSCT) of the abdomen were normal. A working diagnosis of acute pancreatitis was established, and intravenous infusions were initiated. The next day, the patient became hemodynamically unstable with blood pressure 80/60 mm Hg, heart rate 130/min, chills and fever of 39.5 °C, and oliguria. There was remarkable guarding and rebound tenderness in the epigastrium. The blood analysis revealed the following: WBC—9.9 × 109/L; total bilirubin—76 µmol/L; direct bilirubin—52 µmol/L; amylase—214 U/L; CRP 245 mg/L; ASAT—161 U/L; ALAT—132 U/L; GGT—272 U/L; urea—15.7 mmol/L; and creatinine—2.77 mg/dL. She was taken to the operating room for exploration, which revealed local peritonitis and phlegmon of the RL. Resection of the RL was performed. The microbiological analysis showed Klebsiella varicola. The patient had an uneventful recovery and was discharged on the 5th postoperative day. In the next months, the patients had several readmissions due to mild cholestasis and pancreatitis. The magnetic resonance demonstrated a duodenal diverticulum adjacent to the papilla, located near the junction of the common bile and pancreatic duct. This clinical manifestation and the location of the diverticulum were suggestive of Lemmel’s syndrome, but a papillary dysfunction attributed to the diverticulum or food stasis cannot be excluded. Conclusion: To our knowledge, we report the first association between RL gangrene and Lemmel’s syndrome. We speculate that duodenal diverticulitis with lymphatic spread of the infection or transient bacteriemia in the bile with bacterial translocation due to papillary dysfunction, as well as cholestasis resulting from the diverticulum, could be plausible and unreported causes of the RL infection. The preoperative diagnosis of RL gangrene is challenging because it resembles the most common emergency conditions in the upper abdomen. The present case warrants attention due to the difficult decision to operate based solely on the clinical picture, despite negative imaging results. A high index of suspicion should be maintained in a case of unexplained septic shock and epigastric tenderness, even in negative imaging findings. MSCT, however, is a valuable tool to avert unnecessary operations in conditions that must be managed conservatively, such as acute pancreatitis. Full article
(This article belongs to the Section Surgery)
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