Bilirubin In Patients Research Articles

Absence of Survival Impact from Hepatitis During Immunotherapy in 193 Patients with Advanced Hepatocellular Carcinoma - An Observational Study from Taiwan.

Hepatitis often occurs after initiating immune checkpoint inhibitor (ICI) treatment. The time and grade of hepatitis after ICI starts and the prognostic role of immune-related hepatitis in patients with advanced hepatocellular carcinoma (aHCC) remain unclear. In this real-world analysis, we enrolled aHCC patients receiving ICIs, documented the highest level of liver enzymes during/after ICIs, and analyzed the survival impact of different hepatitis patterns. One hundred and ninety-three aHCC patients receiving ICIs were recruited. During ICIs, 88.6% of patients experienced aspartate transaminase (AST) elevations (Grade III/IV: 7.8%). For alanine transaminase (ALT), 81.3% had elevated levels (Grade III/IV: 3.6%), and 41.5% of patients had elevated bilirubin levels (Grade 3/4: 6.7%). The median AST, ALT, and total bilirubin values significantly increased after ICI treatment initiated (all p < 0.001) and, similarly, after excluding progressive disease (p = 0.014, p = 0.002, p < 0.001). The median time of hepatitis occurrence is from the 4.0th to 15.9th weeks. Multivariable analysis showed that patterns of liver enzyme change of AST and total bilirubin in patients receiving ICIs significantly correlate to overall survival (OS, p = 0.009 and 0.001, respectively). After ICI termination, patients with elevated bilirubin (p = 0.003) and AST (p = 0.005) would indicate poor survival, with adjustment of viral hepatitis and ICI responses. Hepatitis emerges between the 4th and 20th weeks post-ICI initiation. Changes in liver enzymes during ICI therapy do not directly affect OS, implying the safety of ICI use when corticosteroids are promptly administered if clinically indicated.

Analysis of UGT1A1 genotype-phenotype correlation in Chinese patients with gilbert and crigler-Najjar II syndrome

The spectrum of UDP-glucuronosyltransferase (UGT1A1) variants, which are associated with Gilbert syndrome (GS) and Crigler-Najjar syndrome (CNS-II), has been reported in Chinese and western countries. However, the genotype-phenotype correlation of the individual UGT1A1 variants in GS and CNS-II remains to be clarified. To explore the UGT1A1 variant pattern and genotype-phenotype correlations, we enrolled 310 Chinese patients, including 232 patients with GS and 78 with CNS-II. Peripheral blood samples were collected for screening variants in the gene UGT1A1 by a polymerase chain reaction and Sanger sequencing. The correlation between different UGT1A1 variants and clinical phenotypes was analyzed. A total of 21 UGT1A1 variants were identified, including nine novel variants, and constituted 42 UGT1A1 genotypes in the GS and CNS-II patients. The most common UGT1A1 variants were A (TA)7TAA, p.G71R, p.Y486D, p.P364L, and p.P229Q, which were different from western countries. The p.Y486D variant had higher minor allele frequency in CNS-II than in GS whereas the A (TA)7TAA variant had higher minor allele frequency in GS than in CNS-II. The serum total bilirubin and triglyceride had significant differences among 14 recurrent genotypes of UGT1A1, in which the serum total bilirubin in patients with compound p.Y486D (homozygous)/p.G71R variant was significantly higher compared with homozygous A (TA)7TAA, homozygous p.G71R, compound heterozygous A (TA)7TAA/p.G71R and A (TA)7TAA/p.P364L, and combined heterozygous A (TA)7TAA/p.G71R/p.P229Q, while the serum triglyceride in patients with combined A (TA)7TAA (homozygous)/p.P229Q variant was significantly higher compared with compound heterozygous A (TA)7TAA/p.G71R, single heterozygous A (TA)7TAA, single heterozygous p.G71R, and homozygous A (TA)7TAA. The spectrum of UGT1A1 genotypes in Chinese patients was distinct from western countries. There were differential levels of serum total bilirubin and triglyceride in patients with recurrent genotypes of UGT1A1.

Neuropathological implication of high blood bilirubin in patients and model rats with depression

PurposeElevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior. Patients and methodsForty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively. ResultsSerum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress. ConclusionOur findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.

TiO2/Polystyrene Nanocomposite Antibacterial Material as a Hemoperfusion Adsorbent for Efficient Bilirubin Removal and Prevention of Bacterial Infection.

The use of hemoperfusion adsorbents for the removal of bilirubin in patients with liver failure has become a critical treatment. However, the insufficient clearance of bilirubin and the possibility of bacterial infection during hemoperfusion limit the application. In this work, we designed a novel antibacterial bilirubin adsorbent (PSVT) through the suspension polymerization reaction between double-bond functionalized TiO2 nanoparticles and styrene. PSVT showed an excellent bilirubin adsorption ability and antibacterial performance, ensuring efficient clearance of bilirubin in liver failure patients during hemoperfusion and preventing bacterial infection. The experimental results indicated that TiO2 was uniformly dispersed in the microspheres, which improved the mesoporous structure and increased the specific surface area. Composite adsorbent PSVT showed an exceptional bilirubin adsorption capacity, with the maximum adsorption capacity reaching 24.3 mg/g. In addition, the introduction of TiO2 endowed PSVT with excellent antibacterial ability; the ultimate antibacterial rates against Escherichia coli and Staphylococcus aureus reached 97.31 and 96.47%, respectively. In summary, PSVT served as a novel antibacterial bilirubin adsorbent with excellent bilirubin clearance capacity and antibacterial performance, providing excellent application prospects for treating liver failure patients.

The Impact of G6PD Deficiency on Liver Function in Children Under 15

Glucose-6-phosphate dehydrogenase (G6PD) is involved in the first phase of the pentose phosphate pathway (PPP), entailing the reduction of nicotinamide adenine dinucleotide phosphate (NADP+) and the oxidation of glucose-6-phosphate to 6-phosphogluconolactone. A deficiency in the G6PD activity can result in numerous illnesses, including liver diseases. The first three enzymes in PPP are responsible for the oxidative phase. They make NADPH, which is needed to deal with oxidative stress, especially in people who do not have enough G6PD. The study included (90) samples from people with hemolytic anemia (Favzim) and control to determine the levels of G6PD, albumin, total protein, liver function, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin. The results showed that there was a significant decrease (P&lt;0.05) in the serum levels of G6PD in the patients group when compared with the control group. Also, there was a significant increase (P&lt;0.05) in the serum levels of albumin, total protein, ALP, ALT, AST and total bilirubin in patients with the G6PD deficiency when compared with the control group. In addition, this study revealed a strong positive correlation between some biochemical parameters studied, such as: Total protein with TSB (r2 = 0.897), TSB with ALT (r2 = 0.893), AST with ALT (r2 = 0.623) and total protein with ALT (r2 = 0.804).

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06). The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.

Effects of Momordica charantia (MC) Extract on Clinical Symptoms, Parasite Account, Thrombocytes, Total Bilirubin and Direct Bilirubin in Patients with Uncomplicated Plasmodium falciparum Malaria: A Case Report

Clinical symptoms during the treatment of uncomplicated P. falciparum malaria have been reported in several studies. Parasite density in the blood is associated with clinical symptoms, platelet, and bilirubin count. A 52-year-old male, weighing 52 kg, was given one capsule containing 325 mg bitter melon (Momordica charantia) extract for 3 days of treatment. Patients were followed up for 28 days, days 1,2,3,4,7,14,21,28, and peripheral blood microscopic examination and clinical symptoms were carried out. Measurement of platelets, total bilirubin, direct bilirubin D0, D14 and D28. Naranjo Scale, adverse events measurements were taken on D7, no signs of severe malaria, no comorbidities, no history of malaria, blood pressure 110/80 mmHg, peripheral blood parasite examination on D0 found P. falciparum parasites of 31,714/µL, D0 platelet value of 94x10 /mm3, D0 total bilirubin value of 1.3 mg% and D0 direct bilirubin value of 0.6 mµ/mL. On D1 parasite count was 2,400/µL, D2 was 372/µL, D3, D4, D7, D14, D21, D28 no asexual parasites were found again. Clinical symptoms that arose on D0 were nausea, no appetite, sweating, chills, sleep disturbance, dizziness, headache, and weakness with a body temperature of 37°C. After D3 of bitter melon extract treatment, no clinical symptoms were found again. Naranjo scale score based on nurse and pharmacist agreement was 6 (probable) at D7 for the adverse events of nausea and vomiting. There were no reported adverse events such as nausea, vomiting, diarrhea, abdominal pain, cough, sleep disturbance, dizziness, headache and weakness on D2 treatment. Bitter melon extract is effective for uncomplicated malaria P. falciparum, reduces clinical symptoms, and is safe.

Extracorporeal adsorption of protective and toxic bile acids and bilirubin in patients with cholestatic liver dysfunction: a prospective study

BackgroundThe release of toxic bile acids (BAs) in the blood of critically ill patients with cholestatic liver dysfunction might lead to the damage of various organs. Their extracorporeal elimination using the cytokine adsorber Cytosorb® (CS) (adsorption of especially hydrophobic molecules < 60 kDa) might be promising, but data proving a potential adsorption are missing so far.MethodsThe prospective Cyto-SOVLE study (NCT04913298) included 20 intensive care patients with cholestatic liver dysfunction, continuous kidney replacement therapy, total bilirubin concentration > 10 mg/dl and the application of CS into the dialysis circuit. Bilirubin and different BAs were measured pre- and post-CS at defined timepoints (10 min, 1, 3, 6, and 12 h after initiation). Relative reduction (RR, %) was calculated with: 1-left(frac{mathrm{concentration} (mathrm{pre}-mathrm{post})}{mathrm{concentration} (mathrm{pre})}right)*100.ResultsThe median RR for total and conjugated bilirubin after initiation was − 31.8% and − 30.3%, respectively, and decreased to − 4.5% and − 4.8% after 6 h. A high initial RR was observed for the toxic BAs GCA (− 97.4%), TCA (− 94.9%), GCDCA (− 82.5%), and TCDCA (− 86.0%), decreasing after 6 h to − 32.9%, − 32.7%, − 12.8%, and − 14.3%, respectively. The protective hydrophilic BAs showed a comparable RR after initiation (UDCA: − 77.7%, GUDCA: − 83.0%, TUDCA: − 91.3%) dropping after 6 h to − 7.4%, − 8.5%, and − 12.5%, respectively.ConclusionsCytosorb® can adsorb bilirubin and toxic as well as protective BAs. However, a fast saturation of the adsorber resulting in a rapid decrease of the RR was observed. Furthermore, no relevant difference between hydrophobic toxic and hydrophilic protective BAs was detected regarding the adsorption amount. The clinical benefit or harm of the BA adsorption needs to be evaluated in the future.

Assessment of bilirubin levels in patients with cirrhosis via forehead, sclera and lower eyelid smartphone images.

One of the key biomarkers evaluating liver disease progression is an elevated bilirubin level. Here we apply smartphone imaging to non-invasive assessment of bilirubin in patients with cirrhosis. Image data was processed using two different approaches to remove variation introduced by ambient conditions and different imaging devices-a per-image calibration using a color chart in each image, and a two-step process using pairs of flash/ no-flash images to account for ambient light in combination with a one-time calibration. For the first time, results from the forehead, sclera (white of the eye) and lower eyelid were compared. The correlation coefficients between the total serum bilirubin and the predicted bilirubin via the forehead, sclera and lower eyelid were 0.79, 0.89 and 0.86 (all with p<0.001, n = 66), respectively. Given the simpler image capture for the sclera, the recommended imaging site for this patient cohort is the sclera.

Comparative Study of Serum Levels of Gamma-glutamyl Transferase, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), AST:ALT, and Bilirubin in Patients with Chronic Hepatitis

Comparative Study of Serum Levels of Gamma-glutamyl Transferase, Aspartate Aminotransferase (AST), Alanine Transaminase (ALT), AST:ALT, and Bilirubin in Patients with Chronic Hepatitis

Prognostic Value of the AST/ALT Ratio versus Bilirubin in Patients with Cardiogenic Shock.

This study investigates the prognostic value of the aspartate-to-alanine aminotransferase ratio (i.e., AST/ALT ratio) and bilirubin in patients with cardiogenic shock (CS). Despite ongoing improvements regarding the treatment of CS patients, invasive care unit (ICU) mortality in CS patients remains unacceptably high. Limited data regarding the prognostic value of the AST/ALT ratio and bilirubin in patients suffering from CS is available. The authors hypothesize the measurement of liver enzymes during the course of CS may be an easy and feasible method to assess right-heart dysfunction and prognosis in patients with CS. Consecutive patients with CS from 2019 to 2021 were included. Blood samples were retrieved from the day of disease onset (day 1), days 2, 3, 4 and 8. The prognostic value of the AST/ALT ratio and bilirubin was tested for 30-day all-cause mortality. Statistical analyses included univariable t-tests, Spearman's correlations, Kaplan-Meier analyses, as well as multivariable Cox proportional regression analyses. A total of 157 CS patients were included, with an overall rate of all-cause mortality at 30 days of 51%. The median AST/ALT ratio on day 1 was 1.4, and the median bilirubin was 0.63 mg/dL. No association of the baseline AST/ALT ratio (HR = 1.005; 95% CI 0.649-1.558; p = 0.981) and bilirubin (HR = 1.320; 95% CI 0.834-2.090; p = 0.236) with the risk of 30-day all-cause mortality was found. In contrast, the AST/ALT ratio on day 4 was associated with the risk of 30-day all-cause mortality (HR = 2.826; 95% CI 1.227-6.510; p = 0.015), which was still evident after the multivariable adjustment (HR = 2.830; 95% CI 1.054-7.690; p = 0.039). The AST/ALT ratio during the course of ICU hospitalization from day 4-but not the baseline AST/ALT ratio and bilirubin-was associated with an increased risk of 30-day all-cause mortality in CS patients.

ABO/Rh incompatibility in neonatal jaundice: a tertiary hospital based cross sectional study

Background: Neonatal hyperbilirubinemia, defined as a total serum bilirubin level above 5 mg/dl (86 μmol/l). Haemolytic disease of the newborn due to blood group incompatibilities between mother and foetus is one of the commonest cause of hyperbilirubinemia in the newborn. Methods: A Hospital based cross sectional study was conducted among newborns admitted with jaundice. Results: In our study 51 cases of neonatal jaundice were due to ABO incompatibility and among them 24 were having O-A incompatibility and 27 were having O-B incompatibility. The mean serum bilirubin in patients with ABO incompatibility were higher (24.8) than those without ABO incompatibility. Conclusions: In the present study, one third of newborns with neonatal jaundice were having ABO incompatibility. The mean serum bilirubin in patients with ABO incompatibility were higher than those without ABO incompatibility. This highlights the importance of recognizing ABO Rh incompatibility in neonatal jaundice.

Surgical treatment of the perihilar cholangiocarcinoma with portal vein invasion

Background. Perichilar cholangiocarcinoma is a rare type of malignant neoplasm and is 3-7 cases per 100,000 population. Surgical method is the only radical method of treatment, allowing to improve long-term survival results. One of the important and characteristic features of perihilar cholangiocarcinoma is tumor invasion to the area of the portal vein bifurcation, which occurs in 30–45% of cases. Portal vein invasion is the one of the main causes of perihilar cholangiocarcinoma irresectability. However, innovative surgical technologies allow resection of the liver with resection and reconstruction of the portal vein with acceptable mortality.&#x0D; The aim. The aim of our study was to asses results of surgical treatment of perihilar cholangiocarcinoma with (Group 1) and without (Group 2) portal vein invasion.&#x0D; Materials and methods. From 2003 to January 2023 in the Department of Surgery and Liver Transplantation of the Ukrainian National Institute of Surgery and Transplantation, 208 patients with perihilar cholangiocarcinoma underwent major extended liver resections. We compared 93 (46%) patients who received extended liver resection with portal vein resection (Group 1) with 115 (54%) patients who underwent liver resections without vascular reconstructions (Group 2). The average Ca 19–9 in the group 1 was 288 (8 – 1000) U/ml, in the group 2 –262 (10 – 612) U/ml. The level of total bilirubin in patients of the group 1 was 312 (43 – 621) mcmol/l, in the group 2 – 267 (10 – 612) mcmol/l. In view of this, in the preoperative period, 190 (91,3%) patients underwent decompression of the bile ducts, using percutaneous transhepatic cholangiostomy (PTBD) or retrograde endobiliary stenting. For patients with small remnant liver volume less than 40 %, in 80(38,5%) cases we did preoperative PVE of a resected part of the liver. In 9 cases we made simultaneous PVE and PTBD. When choosing the volume of surgical intervention, we proceeded from the tumor type of Bismuth-Corlette classification, invasion into the portal vessels and the depth of the liver lesion. The portal vein reconstruction was in all cases performed in an “end-to-end”. In all cases we made extended lymphadenectomy.&#x0D; Results. All complications were classified according to the Dindo-Clavien classification. Postoperative mortality in the main group was 11.5%. The overall 1, 3, 5-year survival in the group 1 was 96%, 68,3%, 57,4%, respectively. 1, 3, 5-year survival rate in the comparison group 2 was 98,4%, 76,7%, 47,3%, respectively.&#x0D; Conclusions. Aggressive tactics of surgical treatment of perihilar cholangiocarcinoma provides maximum radicality, allows to increase resectability in case of tumor invasion of the portal vein with acceptable mortality and long-term survival.

Association of the changes in hepatic enzymes, bilirubin, and plasma proteins with beta-thalassemia in iron over loaded-patients

Changes in liver enzymes and bilirubin in patients with thalassemia depend on genetic changes and the association of other genetic determinants. Iron overload is associated with increased morbidity in both transfusion-dependent and non-transfusion-dependent thalassemia patients. The main objective was to evaluate hepatic enzymes, bilirubin and plasma proteins in βTM patients and also to study the correlations of these parameters with serum hemoglobin and ferritin concentrations in βTM patients. To achieve this goal, the study was directed on two groups, the first is case group includes 39 patients with βTM and the second control group includes 34 subject. Serum ALT, AST, total bilirubin, albumin and total protein concentrations were measured by UV-Vis Spectrophotometer, while the concentration of serum ferritin was measured by ELISA Kit. Our results showed that there are highly significant differences between beta thalassemia major and ferritin at mean (2942.71) , furthermore there are highly significant differences between beta thalassemia major and liver enzymes at (71.98) for AST , (69.42) for ALT, (6.98) for Total protein, (3.92) for Albumin and (2.32) for Total bilirubin. In addition our findings showed there are Correlations between serum ferritin concentrations and liver function testes in βTM patients, where there are highly significant differences between beta thalassemia major and Alanine transaminase at mean (r = 0.44), while the Correlation between serum hemoglobin concentration and liver function testes showed highly significant differences between beta thalassemia major and aspartate aminotransferase at mean (r = 0.52). The study concluded that the increase in serum liver enzymes (ALT, AST) and total bilirubin concentrations in patients with βTM are indicator to liver dysfunction that is correlated to iron overload.

Metal-organic framework (UiO-66 and UiO-66-NH2)-based adsorbents for bilirubin removal used in hemoperfusion.

Excessive accumulation of bilirubin in patients with hyperbilirubinemia can lead to tissue and organ damage and neurological diseases, and is even life-threatening in severe cases. Hemoperfusion is an effective method for removing bilirubin, but clinically used hemoperfusion adsorbents have unsatisfactory adsorption capacity and kinetics. In order to obtain a safe and efficient bilirubin adsorbent, Zr-based Metal-Organic Framework (MOF) material UiO-66 with high specific surface area and aqueous medium stability was prepared and modified with varying degrees of amination to improve its adsorption capacity. According to adsorption experiments in aqueous solution and simulated plasma, it was confirmed that the unsaturated coordinated zirconium in UiO-66 can effectively induce the aggregation and precipitation of free bilirubin unbound to albumin and the amino group on UiO-66-NH2 has a strong affinity for albumin bound bilirubin. The adsorption effect of UiO-66-NH2 with a high degree of amino modification is significantly stronger than that of UiO-66-NH2 with a low degree of modification. In simulated plasma with a bilirubin concentration of 40 mg dL-1, the adsorption capacities of UiO-66 and UiO-66-NH2-1.9 can reach 69.08 mg g-1 and 81.13 mg g-1. The adsorption isotherm fitting and adsorption kinetics fitting results also show that UiO-66 and UiO-66-NH2 are good adsorbents for bilirubin. In dynamic adsorption, the adsorbents also showed good performance and did not affect the protein in the plasma. The hemolysis test, coagulation time test, and cytotoxicity test confirmed that the bilirubin adsorbents based on UiO-66 and UiO-66-NH2 have good blood compatibility and biocompatibility. This study provides new ideas for the development of a novel bilirubin adsorbent and a theoretical basis for the study of bilirubin adsorption mechanisms.

Bilirubin Removal by Plasmafiltration-Adsorption: Ex vivo Adsorption Kinetics Model and Single Case Report

Background: Extracorporeal removal of bilirubin in patients with severe liver dysfunction is a key blood purification strategy. We conducted an ex vivo study to assess the quantitative capacity to remove bilirubin from plasma of a novel adsorptive cartridge. Methods: We studied a downscaled module of the BS330 Plasma Bilirubin Adsorption Column Cartridge (Jafron Biomedical, Zhuhai City, China) to minimize the plasma requirement in an ex vivo circulation using a solution of hyperbilirubinemic plasma. We measured the bilirubin concentration gap (ΔC) between inlet (Cp_in) and outlet (Cp_out) of the unit and we calculated the removal ratio (RR) as mass adsorbed at different time points. Moreover, we compared the ex vivo model with the bilirubin adsorption kinetics in a patient with acute on chronic liver failure treated with the BS330 cartridge. Results: Bilirubin concentration change across the cartridge at 30 min was 16.5%, and cartridge saturation was reached at 750 min. We used a minimodule downscaled to 1:3 and containing approximately 131 g of BS330 sorbent beads: the device retained 759 mg of bilirubin with a RR of 78.1% and a RR of 42.6% at 120 min. Thus, the adsorption capacity was 5.76 mg of bilirubin per gram of sorbent. Bilirubin adsorption kinetics in our clinical case with a full-scale unit shows a coherent trend with a total bilirubin mass adsorbed after 180 min of 470 mg. Discussion: Our findings provide the first assessment of bilirubin adsorption in an ex vivo model of plasma perfusion and can be used to design interventional studies in humans, providing guidance for an adequate prescription of treatment frequency and duration.

Alkaline phosphatase and bilirubin combined are a powerful predictor of outcome in patients with heart failure and reduced ejection fraction: an analysis of the ATMOSPHERE and PARADIGM-HF trials

Abstract Introduction Bilirubin is a recognized predictor of adverse outcomes in patients with heart failure and reduced ejection fraction (HFrEF), possibly because it is a marker of congestion. Alkaline phosphatase (ALP) is an enzyme produced in many tissues including the biliary ducts and elevated levels are also associated with congestion. Purpose To examine the prognostic value of ALP alone and in combination with bilirubin in patients with HFrEF. Methods The study population was ambulatory patients with HFrEF enrolled in 2 recent clinical trials with similar inclusion and exclusion criteria: ATMOSPHERE (derivation cohort) and PARADIGM-HF (validation). Cut points to define elevated bilirubin and alkaline phosphatase were &amp;gt;17mg/dL and &amp;gt;120 U/L respectively. The composite of cardiovascular death or HF hospitalization, its components, and all-cause death related to elevation of one, other or both of bilirubin and ALP was examined using Cox regression. Univariable and multivariable models with adjustment for other recognized prognostic variables including NT-proBNP were analyzed. Results Of 7016 patients with HFrEF enrolled in ATMOSPHERE, 6870 had a measurement of both bilirubin and ALP at baseline: mean age 63 years, 22% women, mean LVEF 28% and proportion NYHA class III/IV 37%. Bilirubin and ALP were both normal in 4810 (70.0%) patients, bilirubin was elevated in 1393 (20.3%), ALP was elevated in 360 (5.2%) and both were elevated in 307 (4.5%) patients. Patients with elevation of both ALP and bilirubin were older, had lower systolic blood pressure, higher heart rate, higher NT-pro BNP, more clinical features of congestion, more atrial fibrillation and a greater proportion were treated with diuretics and digoxin. The primary endpoint rates (per 100 person-years) were 10.4 (95% CI 9.9–11.0) when both markers were normal, 15.1 (13.9–16.4) when bilirubin was elevated, 12.4 (10.4–14.9) when alkaline phosphatase was elevated, and 25.6 (22.0–29.9) when both markers were elevated (Figure 1). The adjusted hazard ratios (95% CI) were (both biomarkers normal = reference): elevated bilirubin 1.19 (1.07–1.31), P=0.001; elevated ALP 1.03 (0.84–1.26), P=0.81; both elevated 1.45 (1.21–1.73), P&amp;lt;0.001. Elevation of both bilirubin and ALP was a significant independent predictor of the components of the primary outcome and all-cause death, the corresponding hazard ratios for all cause death were 1.12 (0.99–1.25), p=0.06; 1.19 (0.96–1.47), p=0.12; and 1.51 (1.25–1.82), p&amp;lt;0.001. These findings were validated in PARADIGM-HF (Table 1). Conclusions Elevation of ALP in combination with elevated bilirubin identifies a small group of patients at very high risk of adverse outcomes. This may reflect more significant congestion. ALP and bilirubin, inexpensive and routinely measured biochemical tests, are useful prognostic markers in patients with HFrEF. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Relationship between serum indirect bilirubin and prostate volume in patients with benign prostatic hyperplasia: a cross-sectional study

Due to its anti-oxidative effects, bilirubin may protect against a spectrum of diseases. However, the role of bilirubin in patients with benign prostatic hyperplasia (BPH) is poorly explored. This study aimed to investigate the cross-sectional associations between serum indirect bilirubin (IBIL) and prostate volume (PV) in patients with BPH. The medical records of 722 BPH patients were retrospectively analyzed. Body mass index (BMI) was calculated as body weight (kg)/height (m)2. PV was obtained as height (cm) × width (cm) × length (cm) × π/6. Other biochemical indexes were measured by the automatic biochemical analyzer. A univariable linear regression analysis was performed to detect confounders. The IBIL-PV relationship was examined using unadjusted and covariate-adjusted regression models. Furthermore, a segmented linear regression was conducted to analyze the linear trend of IBIL levels and PV. Finally, the sensitivity analysis was stratified by BMI and low-density lipoprotein cholesterol (LDL-C) cutoffs. In this study, the mean age of the patients was 68 (range, 43-93) years. By univariable line regression test, we observed that PV was positively correlated with age, BMI, and LDL-C (β=0.113, 0.096, and 0.135, respectively). IBIL was negatively associated with PV in full adjusted model in men age ≤75 years (β=-1.01; 95% CI: -1.81, -0.22; P=0.01). A statistically significant inverse trend was observed between serum IBIL intervals and PV in patients aged ≤75 years (adjusted for age, BMI, and LDL-C, P for trend =0.015). In sensitivity analysis, significantly negative IBIL-PV relationship only existed in men with normal BMI (adjusted β=-1.328; 95% CI: -2.467, -0.190; P=0.022), overweight men (adjusted β=-1.296; 95% CI: -2.519, -0.074; P=0.038), and men with normal LDL-C level (adjusted β=-1.017; 95% CI: -1.869, -0.164; P=0.019). IBIL is negatively associated with PV in the non-obese population ≤75 years with normal LDL-C. These results suggest that higher serum IBIL possibly provides a degree of protection to BPH by mitigating oxidative stress (OS) related to aging and lipid peroxidation. Nevertheless, these preliminary findings from a single-center, retrospective study have limitations and need to be confirmed by future studies.

Association of UGT1A1 Genetic Variants with Increases in Bilirubin Levels

Association of UGT1A1 Genetic Variants with Increases in Bilirubin Levels

The relationship between serum bilirubin levels and early neurological improvement in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator

Background &amp; Objective: Acute ischemic stroke is defined as the development of sudden neurological deficits resulting from a focal injury due to vascular occlusion in the central nervous system. Intravenous tissue plasminogen activator (t-PA) therapy in these patients is an internationally accepted, evidence- based effective treatment. Previous data suggest that increased serum bilirubin may reflect the intensity of oxidative stress associated with stroke severity. This study aimed to investigate the effect of bilirubin levels on early neurological improvement after intravenous t-PA treatment and whether bilirubin is a determinant in in-hospital mortality. Methods: The determinant role of admission bilirubin levels in the severity of stroke, in-hospital mortality and early neurological improvement after intravenous t-PA was investigated. An independent association of bilirubin with mortality and neurological improvement were identified by multivariate logistic regression analysis. Results: A total of 184 ischemic stroke patients who received intravenous t-PA were included in the study. Serum direct bilirubin, indirect bilirubin, and total bilirubin of patients in the group without early improvement were significantly higher than the group with improvement (p= 0.041, p= 0.030, p= 0.026, respectively). Also, in binary logistic regression analysis, total bilirubin was found to be an independent predictor for early neurological improvement (OR 6.257, 95%CI 1.482-26.413, p=0.013). Conclusions: There was a significant relationship between the severity of the stroke and in-hospital mortality and increased serum bilirubin levels in our study. Again, there was a significant relationship between the lack of early neurological improvement after intravenous t-PA and increased serum bilirubin levels, and serum direct bilirubin levels were independent predictor of neurological improvement.