Bilirubin Research Articles (Page 1)

This study analyzed clinical data and hematological parameters from 3072 patients undergoing thalassemia screening at Guangdong Provincial People's Hospital, investigating the correlation between non-thalassemic hematologic diseases and elevated fetal hemoglobin (HbF) in Guangdong. Results revealed a significant correlation and identified non-thalassemic hematologic diseases as an independent risk factor for HbF elevation (OR = 13.36, P < 0.001), indicating a substantially higher risk than that of non-hematologic disease patients. Among patients with elevated HbF, significant parameter differences emerged: non-thalassemia hematologic disease patients differed from mild β-thalassemia patients with elevated HbF in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), red cell distribution width-coefficient of variation (RDW-CV) (P < 0.05); Significant differences in MCV, MCH, RDW-CV, creatinine (CREA), ferritin (Ferr), total bilirubin (TBIL) and direct bilirubin (DBIL) were found between patients with non-thalassemic hematologic diseases and moderate-to-severe β-thalassemia with elevated HbF levels (P < 0.05). Furthermore, significant differences existed between mild and moderate-to-severe β-thalassemia patients with elevated HbF in MCV, MCH, Ferr, TBIL and DBIL (P < 0.05). This research delineates the epidemiological characteristics of hematologic disease-associated HbF elevation in Guangdong, addressing a regional knowledge gap and providing a foundation for clinical risk stratification. Analysis of these differential hematologic indicators deepens understanding of non-thalassemia disease progression, offers clinicians targeted diagnostic and therapeutic strategies, facilitates early detection and intervention, and contributes to broader hematologic research and discipline development.

Since the causal relationship between cholelithiasis and serum bilirubin levels and hepatobiliary and pancreatic malignancies has been inconclusive and inconsistent for a long time, to control confounding factors and reverse causality as much as possible, this paper adopted a Mendelian randomization (MR) study to reveal further the causal relationship between different exposure factors and hepatobiliary and pancreatic malignancies. This study selected 4 exposure factors, including cholelithiasis, serum total bilirubin, direct bilirubin, and indirect bilirubin, by double-sample and bidirectional MR method. The results were as follows: gallbladder carcinoma, liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PADC) were selected as the outcome, and significance level (P < 5e-08) was used as the filtering criterion to select genetic variation as the instrumental variable for follow-up analysis. Then, we calculated the odds ratio between exposure and outcome to show the causal relationship between different exposure factors and outcome. A series of sensitivity analyses were conducted to verify the conclusions' reliability. There was a causal relationship between direct bilirubin and gallbladder cancer, and direct bilirubin was a risk factor for gallbladder cancer (odds ratio = 3.07, 95% confidence interval = 1.02-9.22, P = .04). We then performed a reverse MR analysis on this analysis to further analyze the possible reverse causality between the 2 and found no reverse causality between the 2 (P = .22). At the same time, other exposure factors in the study did not show a causal relationship with the outcome. This study showed that serum direct bilirubin is a risk factor for gallbladder cancer. The conclusion was statistically significant (P = .04), and reverse MR excluded the reverse causal association between the 2. Cholelithiasis, serum total bilirubin, and indirect bilirubin were not causally associated with gallbladder cancer, and none of the exposure factors in the study showed a causal association with hepatocellular carcinoma and pancreatic cancer.

A 30-year-old man presented with long-standing, treatment-resistant psychiatric symptoms including compulsive wandering, hallucinations, and obsessive behaviors. Physical examination revealed deep yellow sclera present since childhood. Genetic testing identified compound heterozygous mutations in the UGT1A1 gene, confirming Crigler–Najjar syndrome type II. Initiation of phenobarbitone and adjunctive therapy led to a marked reduction in serum bilirubin and clinical symptoms. This case highlights the possibility of bilirubin-induced neurological dysfunction presenting in adulthood as a chronic psychiatric condition.

Although direct-acting antiviral agents (DAAs) have significantly increased the cure rate of hepatitis C, the risk factors for virological recurrence and dynamic changes in liver and kidney functions after treatment in the real world still need to be further clarified. A total of 196 patients with hepatitis C virus (HCV) infection admitted to Henan Infectious Disease Hospital from January 2022 to July 2025 were retrospectively included. Baseline data and laboratory indicators at 12 weeks after the end of DAA treatment, sustained virological response (SVR) rate at 12 and 24 weeks after the end of treatment were collected. Changes in liver function, noninvasive liver fibrosis score and safety indicators before and after treatment were compared. The binary logistic regression model was used to analyze the influencing factors of recurrence in patients with HCV. The virological recurrence rate after DAA treatment was 5.10% (10/196), and platelet count, albumin, total bilirubin, alanine aminotransferase, aspartate aminotransferase, α-fetoprotein, and aminotransferase to platelet ratio index decreased significantly after treatment (all P < .05). All 10 relapsed patients achieved SVR12, while 4 did not reach SVR24. The time interval from achieving SVR12 to relapse ranged from 5 to 63 weeks. The results of logistic multivariate analysis showed that a previous history of hepatitis C treatment and concurrent HIV infection were risk factors for hepatitis C recurrence in patients. In this real-world cohort, DAA therapy achieved high 12-week efficacy (SVR12 100%), but 5.10% of patients experienced virological relapse within 63 weeks. Achievement of SVR12 was accompanied by significant improvements in liver function and noninvasive fibrosis scores. Prior HCV treatment experience and HIV coinfection were independent predictors of relapse, underscoring the need for prolonged RNA monitoring in these subgroups.

Major depressive disorder (MDD), a leading global public health concern, exhibits high comorbidity with overweight/obesity. While emerging evidence implicates shared gut microbial dysregulation in both conditions, the identification of specific microbial biomarkers and their interaction with metabolic pathways in comorbid MDD-obesity remains poorly characterized. Our study investigated gut microbiota signatures in patients with MDD, and evaluated their modulation by overweight/obesity comorbidity. A total of 53 patients with MDD and 92 healthy controls (HCs) underwent 16S rRNA gene sequencing. The KEGG function analysis was performed with potential differential microbiota. Correlation analysis related to bacterial taxa, biochemical parameters, and clinical indexes was aimed to indicate the specific metabolic dysregulation and gut microbiota imbalance in MDD, and whether these biomarkers were affected by the comorbidity of overweight/obesity. Sixty-three bacterial genera showed differential abundance between MDD and HCs. Notably, Succinivibrio, Megamonas, and Bifidobacterium demonstrate significant distinctions between overweight-MDD and normal weight-MDD. The significantly altered metabolic pathways between MDD and HC primarily involve the biosynthesis and metabolism of long-chain unsaturated fatty acids. Within the MDD group, BMI demonstrated pairwise negative correlations with Bifidobacterium and total bilirubin (TBIL), while positively associating with Fusobacterium and alanine transaminase (ALT). This study provides novel insights into the interplay between gut microbiota dysbiosis and metabolic perturbations in MDD. Despite intriguing associations between BMI and specific microbial taxa within the MDD group, the preliminary nature of these associations necessitates validation through larger cohorts, multi-omics approaches, and longitudinal designs.

End-stage liver disease continues to present a major clinical challenge, for which liver transplantation (LT) remains the only treatment capable of restoring long-term survival and organ function. Despite advancements in perioperative care and surgical techniques, predicting post-transplant outcomes remains an area of considerable uncertainty. The neutrophil percentage-to-albumin ratio (NPAR), derived from standard blood tests, has emerged as a marker reflecting both systemic inflammation and nutritional status. While NPAR has shown prognostic potential in various liver-related conditions, its role in LT has not been fully clarified. We retrospectively analyzed data from 167 adult patients who underwent LT between 2012 and 2022. Patients were stratified by post-transplant survival status. Preoperative variables - including serum albumin, model for end-stage liver disease (MELD) score, and NPAR - were compared between survivor and non-survivor groups. Receiver operating characteristic analyses were performed to evaluate the predictive performance of these parameters individually and in combination. Significant differences in albumin, total bilirubin, MELD score, and NPAR were observed between survivor and non-survivor groups (P < .05). Individually, both NPAR and MELD demonstrated limited predictive value (AUC = 0.387 and 0.383, respectively). However, their combined application significantly improved discriminatory ability (AUC = 0.654, P = .007), suggesting a complementary interaction. Although NPAR alone is not a strong standalone predictor of post-transplant survival, its integration with the MELD score enhances prognostic accuracy. These findings support the role of NPAR as an adjunct parameter in refining pre-transplant risk assessment.

Immunoglobulin G4 (IgG4)-related pancreatobiliary disease typically manifests as obstructive jaundice, complicating therapeutic choices. Glucocorticoids (GCs) are the primary treatment with many challenges, including high recurrence rates and patient tolerance variability. Endoscopic biliary drainage (EBD) is used to alleviate obstruction, but its role during treatment in IgG4-related pancreatobiliary disease is still contested. There remains a paucity of research comparing the potential benefits of combination therapy with GCs and EBD versus GCs monotherapy. This retrospective study divided 55 IgG4-related pancreatobiliary disease patients into two groups: GCs and GCs + EBD groups. We collected clinical data at the 1st, 3rd, 6th, and 12th months post-treatment to compare treatment efficacy, complication rates, and recurrence. Furthermore, logistic regression was used to analyze independent risk factors for recurrence. The results demonstrated that both treatment regimens significantly reduced total bilirubin (TBIL) and IgG4 levels within one year. The common bile duct diameter significantly decreased at the 6th and 12th months post-treatment compared to baseline. Except for significantly greater TBIL improvement in the GCs+EBD group at the 12th month, no other statistically significant differences were observed between groups. No statistically significant difference was observed in the cumulative recurrence rate within one year after treatment between the GCs and GCs+EBD groups. Finally, we identified elevated baseline IgG4 levels as an independent risk factor for post-treatment recurrence. The combination therapy of GCs and EBD did not exhibit significant differences in immunologic remission, complication rates, or recurrence compared with GCs monotherapy for IgG4-related pancreatobiliary disease. Nonetheless, EBD showed certain benefits in alleviating biliary obstruction.

The consumption of food processed with thermally abused oil has increased significantly in developing countries due to the economic situation. The thermally abused oils are known to be produced along with a variety of toxic compounds that may be deleterious when consumed. The study evaluates the nephroprotective and hepatoprotective effects of Curcuma longa and Punica granatum of female Wistar rats fed thermally abused oil. Forty (40) Female Wistar rats were divided into eight groups. Each receives either standard rat chow or standard rat chow prepared with thermally abused oil. Four groups were subjected to treatment with Curcuma longa and/or Punica granatum supplements over a period of twelve weeks. Standard chemical methods were used to determine markers of kidney and liver functions. The rats fed with thermally abused oil supplemented diets shows significantly (p&lt;0.05) higher Na+ (158.00±0.58 mmol/L), Cl- (113.00±2.08 mmol/L), HCO3- (22.67±0.33 mmol/L), creatinine (30.00±0.58 µmol/L) and Urea (1.03±0.03 mmol/L) compared with the groups that received standard rat chow and treatments. Only K+ (4.47±0.19 mmol/L) shows a significantly (p&gt;0.05) lower concentration in the group fed thermally abused oil-supplemented diet compared to the normal control and treatment groups. The liver indices shows significantly (p&lt;0.05) lower serum Total protein (33±0.33 g/L), albumin (11±0.67 g/L) and conjugated bilirubin (0.12±0.01 mg/dL) but significantly (p&lt;0.05) higher serum Globulins (21.33±0.88 g/L), AST (33±0.58 µ/L), ALP (449±0.58 µ/L), ALT (24.67±0.33 µ/L) and Total bilirubin (1.90±0.06 mg/dL) in group fed thermally abused oil based diet compared to the normal control and treatment groups. The groups supplemented with Curcuma longa and/or Punica granatum exhibit improved conditions compared to those fed diets supplemented with thermally abused oil. The research recommends supplementing diets with Curcuma longa and/or Punica granatum, fed diets supplemented with thermally abused oil to protect the liver and kidneys from damage.

Background: Neonatal cholestasis is a disorder that develops in the first few months of life and is characterised by an increase in direct (conjugated) bilirubin and jaundice due to defective bile synthesis or excretion. Objective: To observe the clinical manifestation and outcome of neonatal cholestasis. Methods: This was a hospital‑based cross‑sectional study carried out among 50 children attending the Department of Pediatrics, Bangladesh Shishu Hospital &amp; Institute (BSH&amp;I), between January 2023 and December 2023. Cholestasis was considered to be conjugated bilirubin levels above 1 mg/dL when serum total bilirubin levels were below 5 mg/dL, or conjugated bilirubin was more than 20% of total when total bilirubin levels were above 5 mg/dL. Children with Jaundice due to other reasons than cholestasis were excluded from the study Results: Among the neonatal cholestasis cases majority (72%) were intrahepatic and 28% were extrahepatic cholestasis. Regarding etiology 13(26%) were idiopathic neonatal hepatitis, 12(24%) biliary atresia, 10(20%) were infection. Mean age of onset for extrahepatic cholestasis was 6.7±1.4 days, while for intrahepatic cholestasis it was 8.2±2.8 days. Mean age of admission for extrahepatic cholestasis was 78.9±21.8 days, while for intrahepatic cholestasis it was 75.4±16.9 days (p&gt;0.05). Male 42.9% had extrahepatic cholestasis, whereas 21 (58.3%) had intrahepatic cholestasis (p&gt;0.05). Twelve cases (85.7%) of persistent pale stool were found in extra-hepatic cholestasis, while eleven cases (30.6%) were detected in intra-hepatic cholestasis, which was substantially higher in terms of clinical presentation (p&lt;0.05). Significantly higher improvement were found in intra hepatic cholestasis then Extra hepatic cholestasis [24(66.7%) vs 1(7.1%), p&lt;0.01). Regarding mortality 7(50%) cases died in extra hepatic choleasis and 7(19.4%) died in Intra hepatic cholestasis (p&lt;0.001). Conclusion: Common etiological factors of neonatal cholestasis include idiopathic newborn hepatitis, biliary atresia, infection, metabolic abnormalities, and hereditary cholestatic diseases. Extra-hepatic cholestasis was associated with persistent pale stool. Treatment seeking in tertiary care hospital was delayed. Intrahepatic cholestasis showed significantly better results than extrahepatic cholestasis. J Shaheed Suhrawardy Med Coll 2024; 16(1): 14-18

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming more common among adolescents, but non-invasive biomarkers for early detection are still limited. Liver-expressed antimicrobial peptide-2 (LEAP-2), a ghrelin receptor antagonist, has been connected to obesity and liver fat buildup in adults, but pediatric data are limited. This study investigates the hypothesis that higher levels of LEAP-2 are associated with hepatic steatosis and the role of LEAP-2 serum levels in the earlier and easier diagnosis of MASLD in children. Methods: In this cross-sectional study, 51 adolescents aged 12–18 were divided into three groups: one with MASLD and obesity (MASLD-Ob) (confirmed hepatosteatosis by imaging studies such as magnetic resonance or ultrasound, along with at least one cardiometabolic criterion and a body mass index (BMI) &gt; 2 SD) (n = 19), another with obesity without any liver pathology or MASLD (BMI &gt; 2 SD) (n = 14), and healthy controls (n = 18). The controlled attenuation parameter (CAP) was measured using FibroScan® Mini + 430 (Echosens SA, Créteil, France), and serum ghrelin and LEAP-2 levels were determined via ELISA. Correlations between LEAP-2, ghrelin, CAP, BMI z-score, and metabolic parameters were analyzed. Results: LEAP-2 and ghrelin levels among the three groups were similar (p = 0.148, p = 0.515). A positive correlation was observed between LEAP-2 levels and CAP values in the obese group (both the MASLD-Ob and obesity groups) (r = 0.379, p = 0.030). When a cutoff of 240 dB/m was used, the median LEAP-2 level in cases above this value was 2.20 ng/mL, compared to 1.37 ng/mL in cases below it (p = 0.021), which was significantly different. When analyzing the obese group (both the MASLD-Ob and obese groups) a statistically significant correlation was found between serum LEAP-2 levels and CAP, AST, GGT, and total bilirubin values (r = 0.379, p = 0.030; r = 0.369, p = 0.035; r = 0.369, p = 0.035; r = 0.357, p = 0.049, respectively). Conclusions: Interventional imaging methods and biomarkers for diagnosing and monitoring hepatosteatosis have become well-established in the literature. However, since these tests are not available at all centers and can be costly, there is an increasing search for other easily accessible diagnostic and follow-up parameters. LEAP-2 could be a promising non-invasive biomarker for pediatric MASLD, especially when used alongside CAP measurements. The application of this biomarker in pediatric MASLD provides valuable data to help identify and monitor the condition in adolescents. We believe our study offers strong evidence to support further research and the development of drug treatments for MASLD that aim to reduce plasma LEAP-2.

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.

Despite dosing protocols and tight therapeutic drug monitoring (TDM), tacrolimus concentrations remain highly variable in pediatric liver transplant (LTx) recipients during the first month post-transplantation. The objective of this study was to describe weight-adjusted tacrolimus concentration-to-dose (C/D/kg) ratios and to identify physical, clinical, and laboratory parameters associated with interpatient pharmacokinetic (PK) variability in hospitalized children during the first month post-LTx. In this single-center retrospective cohort study (January 2018-October 2021), we calculated C/D/kg ratios for 36 LTx recipients aged 0-2years. Descriptive statistics and linear mixed models characterized changes in tacrolimus C/D/kg ratios over time, and we determined the percentage of concentrations within six predefined ranges (0-4, 4-6, 6-8, 8-10, 10-15, and >15μg/L). In total, 524 trough concentrations of orally administered tacrolimus were analyzed. Tacrolimus C/D/kg ratios ranged from 0.19 to 0.75, demonstrating substantial interpatient variability. Time post-transplantation, alanine aminotransferase, aspartate aminotransferase, total bilirubin, coadministration of corticosteroids, spironolactone, fluconazole, fentanyl, amlodipine, flucloxacillin, and ciprofloxacin were significantly associated with interpatient variability (P<0.05 for all). In the first week, 40.0% tacrolimus trough concentrations were below 4μg/L, and using TDM the distribution shifted towards the therapeutic mid-range (6-10μg/L). TDM of tacrolimus is often not enough to obtain the concentrations in the therapeutic range. Identifying cofounders for variability a priori is essential for guiding efficient and accurate dosing, shifting the focus from reactive TDM towards better dosing strategies that improve PK predictions and ultimately improve therapy for pediatric LTx recipients.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease with various clinical manifestations. Multiorgan involvement is associated with a worse prognosis. SLE in pediatrics is rare, with an estimated incidence of 0.3–0.9 per 100,000 children. Case: A 16-year-old Asian girl was admitted with pain, swelling, and a bluish discoloration with blisters on the right leg for 6 days. She had a history of facial rash, hair loss, and oral ulcer. Doppler ultrasound showed deep vein thrombosis in the right lower extremity with acute thrombosis, with visible soft-material intraluminal thrombus. Coombs test was 4+ positive. Elevated total bilirubin 2.2 mg/dL, indirect bilirubin 0.9 mg/dL, and elevated reticulocyte 5.2%. ANA test result is borderline 0.8, and anti-DS DNA negative. CT angiography showed proximal total occlusion of the right dorsalis pedis artery, DVT along the external iliac vein, femoral vein, and popliteal vein to the proximal 1/3 of the right posterior tibial vein. Diagnosis of an autoimmune disease leading to autoimmune hemolytic anemia and deep vein thrombosis was suspected. Her condition improved after corticosteroids and anticoagulant treatment. Conclusion: A 16-year-old girl was diagnosed with autoimmune hemolytic anemia, deep vein thrombosis, and suspected systemic lupus erythematosus. Early recognition of unusual manifestations of SLE is important.

Background: Dotinurad (DOT) has demonstrated beneficial metabolic effects in preclinical models as a selective uric acid reabsorption inhibitor. However, its clinical impact on steatotic liver disease (SLD) with hyperuricemia (HU-SLD) remains unclear. Methods: This observational pilot study evaluated 33 patients with HU-SLD (Metabolic dysfunction-associated steatotic liver disease: n = 20; Metabolic dysfunction-associated alcohol-related liver disease: n = 1; Alcohol-related liver disease: n = 12) treated with DOT for at least 6 months. Laboratory parameters were assessed at baseline and at 6 months. The primary outcomes were changes in serum uric acid levels, hepatobiliary function markers, and renal function markers. Results: DOT significantly reduced serum uric acid levels from 8.4 (7.7–9.0) to 6.0 (5.9–6.8) mg/dL at 6 months (p &lt; 0.001). Regarding hepatobiliary markers, gamma-glutamyl transferase decreased from 47 (30–78) to 43 (27–54) U/L (p = 0.042) and total bilirubin decreased from 0.6 (0.5–1.0) to 0.6 (0.4–0.7) mg/dL (p = 0.023). Significant but modest improvements in renal function were also observed, with serum creatinine decreasing from 1.1 (0.9–1.3) to 1.0 (0.9–1.1) mg/dL (p = 0.010) and estimated glomerular filtration rate increasing from 55.6 (44–67.3) to 56.6 (48.8–71.5) mL/min/1.73 m2 (p = 0.007). No significant changes were observed for aspartate aminotransferase, alanine aminotransferase, fibrosis-related markers, lipid profiles, or glycemic markers. Moreover, no treatment discontinuations or adverse events were recorded during the study period. Conclusions: DOT effectively reduced serum uric acid and modestly improved renal and hepatobiliary parameters in HU-SLD without any patient-reported complications. These real-world findings support the potential of DOT as a well-tolerated therapeutic option beyond urate lowering and warrant further investigation in larger, controlled studies.

Background: Owing to its antioxidant activity, unconjugated bilirubin (UCB) has been shown to have protective effects against oxidative stress-mediated diseases, including coronary artery disease (CAD). An original study on UnaG, a fluorescent protein that emits green fluorescence upon binding to UCB, has revealed the presence of bilirubin in high-density lipoprotein (HDL) particles. However, quantifying UCB in HDL particles has been hampered by the overwhelming amount of albumin-bound UCB in blood samples. Accordingly, the relationship between HDL-bound UCB levels and CAD recurrence has remained unclear. Hypothesis: Higher HDL-bound UCB levels are associated with reduced CAD recurrence. Therefore, accurate quantification of HDL-bound UCB may be a predictive biomarker for CAD recurrence. Methods: We have developed an efficient technique for preparing albumin-free HDL from serum using the dextran sulfate precipitation method. We utilized apoUnaG to establish a direct fluorometric method for quantifying UCB in HDL samples. We measured HDL-bound UCB levels in blood samples from 100 patients who had undergone percutaneous coronary intervention. A comparison was made between the presence and absence of revascularization. Results: SDS-PAGE analysis and biochemical tests revealed that the HDL fraction for UCB assay was completely devoid of albumin. In addition, HDL cholesterol levels in the HDL fraction were strongly correlated with those in serum, validating the recovery efficiency of our method for HDL purification. apoUnaG was able to quantify HDL-bound UCB in serum samples from CAD patients, with measured UCB levels ranging from 0.00781 μM to 0.5 μM. Remarkably, HDL-bound UCB levels were significantly lower in the recurrence group than in the non-recurrence group {median (IQR): 0.0531 (0.0285–0.126) and 0.0911 (0.0495–0.171), respectively; p = 0.02}. In contrast, no significant differences were observed in the serum levels of UCB and HDL-cholesterol between the two groups. Conclusion: The combination of the classic dextran sulfate precipitation method and the recently discovered eel fluorescent protein is a simple yet reproducible technique for quantifying UCB in HDL fractions. High levels of HDL-bound UCB were associated with a reduced risk of CAD recurrence.

Introduction/Background: Heart failure (HF) care is still steered almost solely by left-ventricular ejection fraction (LVEF), yet outcomes remain sub-optimal, suggesting that the HFrEF/HFmrEF/HFpEF scheme is too crude for precision therapy. Research Question/Hypothesis: We hypothesised that unsupervised machine learning (ML) applied to routinely collected variables could yield a more informative HF stratification than the conventional LVEF-based framework. Goals/Aims: To develop an ML-derived multidimensional HF classification, test its prognostic performance, and compare it with existing LVEF categories. Methods/Approach: We analysed 13,238 patients in the nationwide JROAD-HF registry in Japan. Forty-six clinical, laboratory, and echocardiographic variables entered a latent-class model; the cohort was randomly split 1:1 into discovery and internal-validation sets to assess robustness. (Figure 1) Clinical endpoint defined as a composite of 5-year cardiovascular death and heart failure readmission. Results: The model identified three phenogroups by minimum Bayesian Information Criteria. Phenogroup 1 “Advanced Low-Output HF” (predominantly male, age 73.6 ± 12 years) showed severe systolic dysfunction (LVEF 35.5 %), renal impairment, and heavy burdens of ischemic heart disease (52 %) and cardiomyopathy (29%). Phenogroup 2 “Early Afterload-Mismatch HF” (predominantly male, age 68.8 ± 12 years) was the youngest, markedly hypertensive, with intermediate LVEF (41.9%) and diverse etiologies. Phenogroup 3 “Elderly HFpEF-like HF” (predominantly female, age 84.5 ± 7 years) was lean and anemic, with preserved LVEF 53.5%, atrial fibrillation (45%), and valvular disease (42%). The four most discriminative variables were age, total bilirubin, LV diastolic diameter, and serum hemoglobin rather than LVEF and yielded an adjusted Rand index of 0.94 in the validation set, indicating excellent reproducibility. Five-year Kaplan–Meier curves showed the lowest mortality in Phenogroup 2 and the highest in Phenogroup 1 (log-rank p &lt; 0.001), whereas LVEF categories showed no significant separation (p = 0.267) (Figure 2 A and B). Conclusions: ML-driven phenomapping of routine hospital data delineated three distinct HF groups that outperformed the traditional LVEF classification in prognostic discrimination.

Background: Neonatal jaundice, characterized by yellow discoloration of the skin and sclera due to bilirubin deposition, remains one of the most common neonatal problems. Polycythemia in neonates increases red blood cell mass, leading to accelerated breakdown and hyperbilirubinemia, which can progress to severe complications such as kernicterus. Objective: To determine the frequency of neonatal jaundice among polycythemic infants admitted to the neonatal intensive care unit (NICU). Methodology: A cross-sectional study was conducted at the Department of Pediatrics, Hayatabad Medical Complex, Peshawar, from July 2020 to January 2021. A non-probability consecutive sampling technique was used, and a total of 167 neonates were enrolled based on WHO sample size calculation. Inclusion criteria were neonates less than one month old, gestational age between 31–40 weeks, weight 1500–4600 g, and diagnosed with polycythemia. Neonates with blood disorders, syndromic features, or jaundice developing after three weeks were excluded. Data were collected through structured questionnaires, clinical assessment, and laboratory investigations. Analysis was done using SPSS v20. Results: Among 167 neonates, 108 (65.7%) were male and 59 (35.3%) female, with a mean age of 14.5 ± 7.22 days. Neonatal jaundice was present in 78 (46.7%) infants, and 45 (26.9%) developed kernicterus. Jaundice was significantly associated with male gender, neonatal age &lt;15 days, high hemoglobin levels (&gt;22 g/dL), elevated serum bilirubin, obstetric complications, birth asphyxia, and cephalohematoma (p &lt; 0.05), but not with gestational age. Conclusion: Nearly half of the polycythemic neonates admitted to the NICU developed jaundice, with a considerable proportion progressing to kernicterus. Male gender, higher hemoglobin concentration, and perinatal complications emerged as major risk factors. These findings highlight the importance of early screening and timely intervention in polycythemic infants to prevent severe neurological outcomes. Keywords: Bilirubin, Birth asphyxia, Kernicterus, Neonatal jaundice, Polycythemia.

Liver involvement is a common but variable manifestation of dengue virus infection. This study aimed to evaluate the clinical and biochemical spectrum of dengue hepatitis and its correlation with disease severity in patients presenting to a tertiary care center. A retrospective cross-sectional study was conducted at a tertiary care center from July 2024 to December 2024, including 130 adult patients with laboratory-confirmed dengue infection. Dengue hepatitis was categorized as mild, moderate, or severe based on serum transaminase levels. Disease severity was assessed according to both the World Health Organization (WHO) 1997 and WHO 2009 classification criteria. Laboratory parameters were analyzed in relation to hepatitis severity. Among the 130 patients, 113 (87%) had elevated liver enzymes. Aspartate Aminotransferase Levels (AST) were consistently higher than Alanine Aminotransferase (ALT). Severe dengue hepatitis was significantly associated with WHO 2009 disease severity classification (p&lt;0.001). Total bilirubin levels were significantly elevated in patients with more severe hepatitis, while no significant correlation was observed between platelet count and hepatitis severity. Patients presenting with warning signs and severe dengue had higher frequencies of moderate-to-severe hepatitis. We conclude that hepatic involvement in dengue infection is common and correlates with disease severity. Elevated transaminases, particularly AST, and rising bilirubin levels may serve as early markers of severe dengue. Integration of liver function monitoring into clinical assessment protocols is essential for the timely management of dengue hepatitis.

Introduction: Nearly 1 in 10,000 infants are born with a single ventricular heart, and these children must undergo the Fontan procedure to survive. As of 2020, an estimated 50,000 individuals are alive with a Fontan circulation. Although lifesaving, Fontan procedure is associated with several complications, including Fontan-associated liver disease (FALD). While elevated central venous pressure (CVP) appears to promote FALD, the cellular and molecular mechanisms involved in this unique liver disease are not well understood. Methods: Liver biopsies from Fontan patients were collected at Washington University in St. Louis before heart transplant. Liver tissue was fixed in formalin and embedded in paraffin for H&amp;E and Masson's trichrome staining. Immunohistochemistry, scRNA-seq, and immunofluorescence (IF) were performed. In our preclinical model, mice underwent pIVCL to mimic hepatic congestion and underwent IF, RNA analysis, and snRNA-seq. Results: We recruited 35 patients with a mean age of 18.1 years (SD ±6.6) at the time of liver biopsy. The mean age at the time of the Fontan procedure was 2.4 years (SD ±0.9), with the average duration of Fontan circulation being 13 years. Regarding ventricular morphology, 25 patients (71%) had a single right ventricle, and 10 (29%) had a single left ventricle. The extracardiac conduit was the most common Fontan connection in 23 patients (72%). CVP was elevated in the superior vena cava (SVC) and Fontan conduit, with a mean of 18 mmHg (SD ±3.6). Liver function tests showed a median AST of 30.5 U/L (IQR 29.8), median ALT of 26.5 U/L (IQR 26.9), and median total bilirubin of 1.0 mg/dL (IQR 0.9). The mean APRI score was 0.58 (SD ±1.9), and MELD-XI was 10.2 (SD ±2.9). Fontan liver biopsies and liver sections from pIVCL mice showed sinusoidal dilatation, central hepatocyte dropout, and bridging fibrosis. Multiple areas of CK7-positive biliary metaplastic cells, which originated from HNF4α-positive hepatic progenitor cells, were identified. These areas colocalized with areas of CD68-positive aggregated macrophages and activated hepatic stellate cells (αSMA+). Using snRNA-seq in pIVCL and scRNA-seq in Fontan, we identified the cellular landscape in the cardiogenic liver disease. Conclusions: The interplay between sinusoidal congestion, macrophage activation, and biliary metaplasia in FALD implies a multifactorial pathogenesis that extends beyond passive venous congestion in cardiogenic liver diseases.

The purpose of this study was to evaluate the preventive effects of propylene glycol (PG) or sucrose (SC) in dairy cows with high levels of non-esterified fatty acids (NEFAs) during the close-up period. From July 2021 to August 2022, blood samples were collected from 193 cows between 14 and 7 days prior to the expected calving date in two farms, and 35 multiparous cows with serum NEFA ≥ 0.3 mEq/L were randomly assigned to PG (500 mL/day, n = 11), SC (1000 mL/day of 50% solution, n = 11), and untreated control (HC; n = 13) groups. Treatments were administered orally for 5 consecutive days. Compared with HC cows, the serum NEFA concentration tended to be lower in SC cows at 3 days in milk (DIM) and was significantly lower in PG cows at 14 DIM. Serum β-hydroxybutyrate concentrations tended to be lower in SC cows at 21 DIM. Blood glucose concentrations were higher in both treatment groups at 3 DIM, and the serum total bilirubin concentration remained lower until 14 DIM in PG cows and until 7 DIM in SC cows. At 7 DIM, PG cows showed significantly higher total very low-density lipoprotein levels and PG and SC cows had significantly or tendentially higher low-density lipoprotein triglyceride concentrations. Cows in both treatment groups had significantly reduced culling after calving. These results suggest that prophylactic administration of PG or SC improves energy metabolism by supporting liver function, thereby reducing postpartum culling, with the PG group showing a more consistent effect.