Bilirubin Excretion Research Articles

A superior material with antithrombotic properties serves as a secure adsorbent for the elimination of bilirubin in vitro and in pig models

Hyperbilirubinemia is primarily treated through hemoperfusion, a process that utilizes biomaterials as adsorbents to eliminate excessive bilirubin from the bloodstream. However, extracorporeal circuits are prone to thrombus formation due to the frequent use of blood-contacting devices, potentially leading to treatment failure and adverse clinical outcomes. In this study, using a resin substance treated with sulfated polysaccharides (GLU-ERM-0100), we present a reliable and safe approach for removing excessive bilirubin from blood. The resin’s pore size facilitates bilirubin adsorption, while sulfonic and hydroxyl groups incorporated within the material enable like-heparinization. GLU-ERM-0100 serves as a temporary blood-thinning agent, binding coagulation factors in the extracorporeal circuit, thereby eliminating the need for conventional anticoagulant medications. Both in vitro and animal studies demonstrate the material’s exceptional bilirubin adsorption capacity and effective anticoagulation properties.

Correlation of bilirubin and toxic bile acids in critically ill patients with cholestatic liver dysfunction and adsorber application

Bilirubin is one of the most frequently used laboratory values to monitor critically ill patients with cholestatic liver dysfunction. Besides bilirubin, toxic bile acids (TBAs), which may cause severe organ damage, are typically elevated. A correlation between both parameters seems plausible, but data are lacking. The aim was to investigate whether there is a correlation between bilirubin and TBAs in patients’ blood and whether a compareable reduction can be observed during the use of the adsorber CytoSorb (CS). As part of the Cyto-SOLVE study (NCT04913298), 16 critically ill patients with cholestatic liver dysfunction, bilirubin concentration > 10 mg/dl, continuous kidney replacement therapy and CS-application were investigated. Bilirubin and TBA concentrations were measured from arterial blood at defined time points (before start, after 6 and 12 h). Relative reduction (RR) was calculated using the formula\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\:\\:{\\boldsymbol{RR}}\\:{\\boldsymbol{\\left(\\%\\right)}}=\\frac{{\\boldsymbol{concentration\\left(pre-post\\right)}}}{{\\boldsymbol{concentration\\left(pre\\right)}}}*{\\boldsymbol{100}}$$\\end{document}. A moderate to high correlation between bilirubin and TBA concentration at all defined timepoints (rstart=0.64, p = 0.008; r6h = 0.85, p < 0.001, r12h = 0.72, p = 0.002) was observed. In the first six hours of CS-application, a significant elimination of TBA (median TBA: 30.8→20.1µmol/l, p < 0.001) and bilirubin (median bilirubin: 17.1→11.9 mg/dl, p < 0.001) was observed. The median RR after 6 h was 26.1% and 39.8% for bilirubin and TBA, respectively. No further reduction was observed after 12 h (RRbilirubin: – 0.6%, RRTBA: 1.8%). There was an at least moderate correlation between bilirubin and TBA in patients with cholestatic liver dysfunction. Therefore, bilirubin seems to be a suitable surrogate parameter for TBA elimination during CytoSorb application.

What Happens in the Gut during the Formation of Neonatal Jaundice-Underhand Manipulation of Gut Microbiota?

Jaundice is a symptom of high blood bilirubin levels affecting about 80% of neonates. In neonates fed with breast milk, jaundice is particularly prevalent and severe, which is likely multifactorial. With the development of genomics and metagenomics, a deeper understanding of the neonatal gut microbiota has been achieved. We find there are accumulating evidence to indicate the importance of the gut microbiota in the mechanism of jaundice. In this paper, we present new comprehensive insight into the relationship between the microbiota and jaundice. In the new perspective, the gut is a crucial crossroad of bilirubin excretion, and bacteria colonizing the gut could play different roles in the excretion of bilirubin, including Escherichia coli as the main traffic jam causers, some Clostridium and Bacteroides strains as the traffic police, and most probiotic Bifidobacterium and Lactobacillus strains as bystanders with no effect or only a secondary indirect effect on the metabolism of bilirubin. This insight could explain why breast milk jaundice causes a longer duration of blood bilirubin and why most probiotics have limited effects on neonatal jaundice. With the encouragement of breastmilk feeding, our perspective could guide the development of new therapy methods to prevent this side effect of breastfeeding.

Interplay of OATP1A/1B/2B1 uptake transporters and ABCB1 and ABCG2 efflux transporters in the handling of bilirubin and drugs

Transmembrane drug transporters can be important determinants of the pharmacokinetics, efficacy, and safety profiles of drugs. To investigate the potential cooperative and/or counteracting interplay of OATP1A/1B/2B1 uptake transporters and ABCB1 and ABCG2 efflux transporters in physiology and pharmacology, we generated a new mouse model (Bab12), deficient for Slco1a/1b, Slco2b1, Abcb1a/1b and Abcg2. Bab12 mice were viable and fertile. We compared wild-type, Slco1a/1b/2b1-/-, Abcb1a/1b;Abcg2-/- and Bab12 strains. Endogenous plasma conjugated bilirubin levels ranked as follows: wild-type = Abcb1a/1b;Abcg2-/- <<Slco1a/1b/2b1-/- <Bab12 mice. Plasma levels of rosuvastatin and fexofenadine were elevated in Slco1a/1b/2b1-/- and Abcb1a/1b;Abcg2-/- mice compared to wild-type, and dramatically increased in Bab12 mice. Although systemic exposure of larotrectinib and repotrectinib was substantially increased in the separate multidrug transporter knockout strains, no additive effects were observed in the combination Bab12 mice. Significantly higher plasma exposure of fluvastatin and pravastatin was only found in Slco1a/1b/2b1-deficient mice. However, noticeable transport by Slco1a/1b/2b1 and Abcb1a/1b and Abcg2 across the BBB was observed for fluvastatin and pravastatin, respectively, by comparing Bab12 mice with Abcb1a/1b;Abcg2-/- or Slco1a/1b/2b1-/- mice. Quite varying behavior in plasma exposure of erlotinib and its metabolites was observed among these strains. Bab12 mice revealed that Abcb1a/1b and/or Abcg2 can contribute to conjugated bilirubin elimination when Slco1a/1b/2b1 are absent. Our results suggest that the interplay of Slco1a/1b/2b1, Abcb1a/1b, and Abcg2 could markedly affect the pharmacokinetics of some, but not all drugs and metabolites. The Bab12 mouse model will represent a useful tool for optimizing drug development and clinical application, including efficacy and safety.

Otras enfermedades hepáticas de causa genética, metabólica y endocrinológica

Liver diseases of genetic origin comprise a series of diseases that manifest as abnormalities in liver structure and/or function due to genetic mutations. This update will discuss some of them, such as alpha-1 antitrypsin deficiency (A1AT), Wilson's disease, lysosomal acid lipase deficiency (LAL-D), and other congenital diseases related to bile acid and bilirubin metabolism.Alpha-1 antitrypsin deficiency is an autosomal codominant condition characterized by a decrease in secretion of alpha-1 antitrypsin protein, which acts as an inhibitor of neutrophil elastase. This results in liver and lung damage due to an accumulation of misfolded protein in hepatocytes and uncontrolled elastase activity. On the other hand, in Wilson's disease, an autosomal recessive disorder, mutations in the ATP7B gene impair copper metabolism. This results in an accumulation of toxic copper in the liver and other organs, causing hepatitis, cirrhosis, and neuropsychiatric manifestations. Lysosomal acid lipase deficiency is an autosomal recessive disorder caused by mutations in the LIPA gene. This results in the accumulation of cholesterol and triglyceride esters in lysosomes, leading to hepatomegaly, hyperlipidemia, and premature atherosclerosis. Finally, the set of diseases related to bilirubin and bile acid metabolism involve abnormalities in the production, transport, and excretion of bilirubin and bile acids. They are associated with cholestasis and hepatocellular damage, which can lead to liver failure and death.

PIJAT BAYI DAN PENURUNAN KADAR BILIRUBIN BAYI IKTERIK: A SCOPING REVIEW

Jaundice is a disorder manifested by yellow discoloration of the skin, sclera and mucous membranes due to an increase in total serum bilirubin (TSB) in the circulation which is usually called hyperbilirubinemia. The aim of this study was to determine the effectiveness of massage to reduce bilirubin levels in icteric babies undergoing phototherapy. The type of research was a systematic review with PRISMA method. Data was accessed from; Google Scholar, PubMed, Research gate, One search, Garuda in the period 2013 to 2023. The article is original research, written in English or Indonesian and the research design is in the form of experimental research with designs: quasi experiments and randomized controlled trials. The number of articles that correspond is 7 articles. The research subjects were healthy babies and babies with jaundice. The results of the systematic review are that regular massage therapy in infants with jaundice undergoing phototherapy has an effective effect in reducing total serum bilirubin (TSB), increasing bilirubin excretion with defecation, reducing the duration of hospitalization. This complementary therapy is an effort to increase the effectiveness and efficiency of treating icteric babies during the hospitalization period.

The role of various laboratory parameters associated with obstructive cholestatic jaundice in pancreatic tumor: A case report and literature review

Introduction: Obstructive jaundice can be caused by pancreatic cancer, where most tumors block bilirubin excretion, and excess bilirubin accumulation causes jaundice. Jaundice occurs in more than 65% of pancreatic cancer patients. Jaundice is caused by the location of the tumor, usually located in the head of the pancreas, suppressing the bile ducts and creating a blockage characterized by an increase in bilirubin, especially direct bilirubin. Aspartate transaminase (AST) and alanine transaminase (ALT) may also be elevated in pancreatic cancer patients but to a lesser extent. Case Presentation: A 63-year-old male patient presented with ocular symptoms and generalized jaundice that had lasted for 2 months. Patients also complain of a bloated stomach and feel thin due to continued weight loss. The patient's stool was the color of putty and brown, like viscous urine. A physical examination revealed conjunctival jaundice in both eyes and hepatomegaly. Abdominal ultrasonography (USG) results suggest a pancreatic head mass with a dilated pancreatic duct and edema of the gallbladder with dilated extrahepatic bile duct (EHBD). Laboratory tests showed that the patient had elevated liver function, total bilirubin 11.90 mg/dl, direct bilirubin 8.29 mg/dl, SGOT 33 U/l, SGPT 54 U/l, and three positive urinary bilirubin values. It became clear that. The patient was diagnosed by observing cholestatic jaundice and the differential diagnosis of suspected pancreatic cancer of the head and cholangiocarcinoma. Conclusion: Examining laboratory parameters such as total bilirubin, especially direct bilirubin, liver enzymes SGOT, and SGPT may help localize obstructions, such as those caused by pancreatic tumors causing post hepatic obstructive jaundice.

Correlation between Bilirubin Elimination with the Cytokine Adsorber CytoSorb® and Mortality in Critically Ill Patients with Hyperbilirubinemia

Introduction: Hyperbilirubinemia is often the first evidence for any kind of liver disorder and over one-third of all patients in intensive care units (ICU) show elevated bilirubin concentrations. In critically ill patients, high concentrations of serum bilirubin are correlated with a poor outcome. Therapies to lower bilirubin concentrations are often just symptomatically and their effect on the patients’ outcome is hardly evaluated. Therefore, this study investigates whether the extracorporeal elimination of bilirubin with the cytokine adsorber CytoSorb^® (CS) reduces mortality in patients with hyperbilirubinemia. Methods: Patients with bilirubin concentrations >10 mg/dL at the ICU were screened for evaluation from 2018 to 2020. Patients with kidney replacement therapy and older than 18 years were included. Patients with continuously decreasing bilirubin concentrations after liver transplantation or other liver support systems (i.e., Molecular Adsorbents Recirculating System [MARS^®], Advanced Organ Support [ADVOS]) were excluded. CS therapy was used in clinical routine and was indicated by the treating physicians. Statistical analysis was performed with IBM SPSS statistics utilizing a multivariate model. Primary outcome measure was the effect of CS on the 30-day mortality. Results: Data from 82 patients (mean Simplified Acute Physiology Score [SAPS] II: 74 points, mean bilirubin: 18 mg/dL, mean lactate: 3.7 mmol/L) were analyzed. There were no significant differences in patients with and without CS treatment. The multivariate model showed no significant effect of CS therapy (p = 0.402) on the 30-day mortality. In addition, a significant effect of bilirubin concentration (p = 0.274) or Model for End-Stage Liver Disease score (p = 0.928) on the 30-day mortality could not be shown. In contrast, lactate concentration (p = 0.001, b = 0.044) and SAPS II (p = 0.025, b = 0.008) had significant impact on 30-day mortality. Conclusion: The use of CS in patients with hyperbilirubinemia did not result in a significant reduction in 30-day mortality. Randomized and controlled studies with mortality as primary outcome measure are needed in the future to justify their use.

An Overview on Neonatal Jaundice

A significant proportion of term and preterm infants develop neonatal jaundice. Jaundice in a healthy term infant is the most common reason for readmission to hospital. Jaundice is caused by a significant increase in serum bilirubin levels, largely due to the breakdown of red blood cells. Bilirubin is transported in the blood as 'unconjugated' bilirubin, largely bound to albumin. The bilirubin is converted into a conjugated form by the liver, which is excreted in the bile. Very high levels of unconjugated bilirubin led to neurotoxicity. In most infants, severe hyperbilirubinemia is caused due to an increase in bilirubin production (e.g., due to haemolysis) and thus reducing bilirubin production is a rational approach for its management. The situation can become critical in infants with an associated impaired bilirubin elimination mechanism as a result of a genetic deficiency and polymorphism. The simplest way to reduce bilirubin levels is by phototherapy. Current management of jaundice in the UK is guided by the NICE guideline.1

Analysis of Knowledge and Perception of Pregnant Women about Field Massage as an Effort to Prevent Hyperbilirubin in Newborns

Hyperbilirubinemia is a clinical phenomenon in 80% of premature babies and 60% of aterm babies in the first week of life (Lei et al., 2018). Field massage is a massage in babies that focuses on stimulating the chest and abdomen area. Field massage is a supporting therapy that can increase the excretion of bilirubin. A good knowledge of field massage can change people's perceptions and perspectives on holistic care in newborns. This study aims to determine the level of knowledge and public perception of field massage. This study used a survey method with a questionnaire. The subjects of the study were pregnant women as many as 62 respondents. The results of the bivariate analysis obtained a significant value of 0.002 which showed that there was a relationship between the level of knowledge and the perception of pregnant women about field massage as an effort to prevent hyperbilirubin in newborns.

Effect of Seasonal Variation on the Bilirubin Content and Hematological Indices among Neonates in Southern Gaza, Palestine

BACKGROUND &amp;amp; OBJECTIVES: Premature newborns&amp;rsquo; bilirubin conjugation and excretion mechanisms are undeveloped. Seasonal changes and other variables affect the severity of newborns&amp;rsquo; physiological jaundice. This study examined blood indices, bilirubin levels, and birth season in neonates in the southern Gaza Strip of Palestine.&#x0D; &#x0D; METHODS: A cross-sectional study of 366 neonates aged one to 14 days was conducted in Medical Nasser Complex-Southern Gaza, Palestine.The newborns were divided into four groups based on season of birth: spring (n=72), winter (n=96), autumn (n=103) and summer (n=95). Blood samples were collected in plain vacutainers for assaying bilirubin profile and complete blood count. Bilirubin and complete blood count were assayed by commercial kits. SPSS software was used for data analysis. &#x0D; &#x0D; RESULTS: Indirect and total bilirubin showed significant seasonal variations, whereas direct did not. Spring and winter have increased indirect and total bilirubin. Seasonal hemoglobin levels varied significantly. Red blood cells, hemoglobin, and hematocrit positively correlated with total and indirect bilirubins. &#x0D; &#x0D; CONCLUSION: Spring and winter births exhibited higher indirect and total bilirubin in the first two weeks. The birth season appears to affect newborn jaundice. Short sunshine duration may increase neonatal hyperbilirubinemia risk.

Modern view on pathogenesis, diagnosis and treatment of Gilbert's syndrome

Gilbert’s syndrome is an autosomal recessive inherited disorder of bilirubin glucuronidation characterized by unconjugated hyperbilirubinaemia in the absence of hepatocellular injury or hemolysis. Gilbert’s syndrome is characterized by mutations to the UGT1A1 gene which encodes the enzyme uridine disphosphate glucuronоsyltransferase which is required for the conjugation and subsequent excretion of bilirubin. Most Gilbert’s syndrome patients experience recurrent and short-term episodes of yellowing of the skin and sclera of eyes caused by bilirubin accumulation in the blood. Approximately 30 % of patients with Gilbert's syndrome do not experience any symptoms, but are detected by blood tests that show elevated levels of unconjugated bilirubin. In addition to traditional methods, genetic analysis of the UGT1A1 gene allows us to confirm the diagnosis of Gilbert's syndrome. The article presents modern concepts of the pathogenesis, diagnosis, differential diagnosis and treatment of Gilbert's syndrome. It is of interest to gastroenterologists, internists and general practitioners who treat such patients.

Cyanidin 3-glucoside targets a hepatic bilirubin transporter in rats

One of the organ-specific functions of the liver is the excretion of bilirubin into the bile. Membrane transport of bilirubin from the blood to the liver is not only an orphan function, because there is no link to the protein/gene units that perform this function, but also a poorly characterised function. The aim of this study was to investigate the pharmacology of bilirubin uptake in the liver of the female Wistar rat to improve basic knowledge in this neglected area of liver physiology. We treated isolated perfused livers of female rats with repeated single-pass, albumin-free bilirubin boli. We monitored both bilirubin and bilirubin glucuronide in perfusion effluent with a bio-fluorometric assay. We tested the ability of nine molecules known as substrates or inhibitors of sinusoidal membrane transporters to inhibit hepatic uptake of bilirubin. We found that cyanidin 3-glucoside and malvidin 3-glucoside were the only molecules that inhibited bilirubin uptake. These dietary anthocyanins resemble bromosulfophthalein (BSP), a substrate of several sinusoidal membrane transporters. The SLCO-specific substrates estradiol-17 beta-glucuronide, pravastatin, and taurocholate inhibited only bilirubin glucuronide uptake. Cyanidin 3-glucoside and taurocholate acted at physiological concentrations. The SLC22-specific substrates indomethacin and ketoprofen were inactive. We demonstrated the existence of a bilirubin-glucuronide transporter inhibited by bilirubin, a fact reported only once in the literature. The data suggest that bilirubin and bilirubin glucuronide are transported to the liver via pharmacologically distinct membrane transport pathways. Some dietary anthocyanins may physiologically modulate the uptake of bilirubin into the liver.

A metabolomic-based biomarker discovery study for predicting phototherapy duration for neonatal hyperbilirubinemia.

Phototherapy is a recommended method for the treatment of neonatal hyperbilirubinemia. However, biomarkers for predicting the more effective duration of phototherapy prior to treatment are lacking. Therefore, we aimed to determine novel predictors for the timing of phototherapy from the perspective of metabolomics. A total of 12 newborns with neonatal hyperbilirubinemia were recruited on the day of admission. The infants were divided into a short-duration (<30 hours) phototherapy group and a long-duration (≥30 hours) phototherapy group based on the length of phototherapy treatment. Metabolites in serum samples were then explored using an untargeted metabolomics strategy. In total, 59 of 1,073 significantly different metabolites were identified between the short-duration and long-duration phototherapy groups, including 18 upregulated and 41 downregulated metabolites. The results of metabolomic analysis showed that the differentially expressed metabolites were enriched in glycerophospholipid metabolism, which is closely associated with the excretion of bilirubin. Moreover, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the metabolites were also enriched in alpha-Linolenic acid metabolism and fatty acid elongation. Spearman correlation hierarchical clustering analysis demonstrated that 9 metabolites were negatively correlated with the duration of phototherapy. Metabolites, especially phosphatidylethanolamine (PE) (22:1(13Z)/15:0), phosphatidylcholine (PC) (18:1(9Z)/18:1(9Z)), phosphatidylserine (PS) (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)), had better predictability for the duration of phototherapy [area under curve (AUC): 1; 95% confidence interval (CI): 1-1] than total serum total bilirubin and direct bilirubin (AUC: 0.806; 95% CI: 0.55-1), as revealed by receiver operating characteristic analysis. Our research found that the differential metabolites were associated with the duration of neonatal jaundice and that glycerophospholipid metabolism might have played a role in this biological process. Moreover, metabolites such as PE (22:1(13Z)/15:0), PC (18:1(9Z)/18:1(9Z)), PS (22:0/15:0), 5,6-dihydrouridine, and PE (MonoMe(11,3)/MonoMe(13,5)) could be used as predictors for phototherapy duration in neonatal hyperbilirubinemia and assist with decision-making.

HUBUNGAN USIA GESTASI DAN BERAT LAHIR NEONATUS DENGAN KEJADIAN IKTERUS NEONATORUM DI RSUD DR.M.HAULUSSY AMBON TAHUN 2018-2020

Neonatal jaundice is incident biological on baby that appears because production cell blood red tall and marked low bilirubin excretion with symptom skin colored yellow baby seen weak, urine colored dark until tanned. Reasons neonatal jaundice among other caused because maternal factors, perinatal factors neonate. Study aim for know connection age gestation dan heavy born neonate with jaundice neonatorum at RSUD dr. M. Haulussy Ambon in 2018-2020. Study this is research using design case control, data obtained is secondary data from record medical patients at RSUD dr. M. Haulussy Ambon obtained 154 samples . Data obtained analyzed use Statistical Package for the Social Science (SPSS) 26. Based on the results of the chi-square test, there was a significant relationship between gestational age (p=0.025) and the incidence of neonatal jaundice, as well as neonatal birth weight (p=&lt;0.001). M. Haulussy Ambon 2018-2020.

Activation of Alternative Bilirubin Clearance Pathways Partially Reduces Hyperbilirubinemia in a Mouse Model Lacking Functional Ugt1a1 Activity.

Bilirubin is a heme catabolite and Ugt1a1 is the only enzyme involved in the biological elimination of bilirubin. Partially functional or non-functional Ugt1a1 may result in neuronal damage and death due to the accumulation of unconjugated bilirubin in the brain. The understanding of the role of alternative bilirubin detoxification mechanisms that can reduce bilirubin toxicity risk is crucial for developing novel therapeutic strategies. To provide a proof-of-principle showing whether activation of alternative detoxification pathways could lead to life-compatible bilirubin levels in the absence of Ugt1a1 activity, we used Ugt1−/− hyperbilirubinemic mice devoid of bilirubin glucuronidation activity. We treated adult Ugt1−/− mice with TCPOBOP, a strong agonist of the constitutive androstane receptor (CAR). TCPOBOP treatment decreased plasma and liver tissue bilirubin levels by about 38%, and resulted in the transcriptional activation of a vast array of genes involved in bilirubin transport and metabolism. However, brain bilirubin level was unaltered. We observed ~40% degradation of bilirubin in the liver microsomes from TCPOBOP treated Ugt1−/− mice. Our findings suggest that, in the absence of Ugt1a1, the activation of alternative bilirubin clearance pathways can partially improve hyperbilirubinemic conditions. This therapeutic approach may only be considered in a combinatorial manner along with other treatments.

Effect of clofibrate on reducing neonatal jaundice: a systematic review and meta-analysis.

In neonates, bilirubin tends to be deposited in body tissues, especially the skin and mucous membranes. Jaundice is an early symptom of bilirubin excretion disorders. Therefore, the aim of this study was to investigate the effect of clofibrate on reducing neonatal jaundice. In this systematic review, international databases, including PubMed, Scopus, Web of Science, Embase, Cochrane, and Google Scholar, were searched without time and language restrictions. The reference lists of all studies ultimately included were manually searched. In the 17 articles reviewed, with a sample size of 665 people published between 2005 and 2019, the average weight of the neonates varied from 2,186 g to 4,000 g. Furthermore, the average age of neonates varied from 2 days to 9 days. Four doses of clofibrate (25, 30, 50, 100 mg/kg of neonatal body weight) were used. The bilirubin level of neonates significantly decreased in the intervention group 24, 36, 48, and 72 hours after the start of treatment. Clofibrate administration decreased total serum bilirubin, especially from the second day onwards, and also reduced hospitalization time, hospital costs, and side effects from hospitalization.

Approach to Management of Cholestatic Jaundice

Cholestatic jaundice is a common presenting feature of neonatal hepatobiliary and metabolic dysfunction. Any infant who remains jaundiced beyond age 2 to 3 weeks should have the serum bilirubin level fractionated into a conjugated (direct) and unconjugated (indirect) portion in neonates mainly undirect bilirubin. In cholestasis, the primary failure is of bilirubin excretion, resulting in excess conjugated bilirubin in the bloodstream and decreased bile salts in the gastrointestinal (GI) tract. Because of inadequate bile in the GI tract, there is malabsorption of fat and fat-soluble vitamins (A, D, E, and K), leading to vitamin deficiency, inadequate nutrition, and growth failure. Our case is interesting present in first day of life with conjugate bilirubin which made us look for differential diagnosis, no family history of metabolic disease, 1st consequently, no dysmorphic feature, admitted in NICU as case of cholecystic jaundice for farther investigation, all investigations were done, and patient sent to higher center for farther management.

Prenatal glucocorticoid administration enhances bilirubin metabolic capacity and increases Ugt1a and Abcc2 gene expression via glucocorticoid receptor and PXR in rat fetal liver.

Jaundice is especially common in premature infant born before 35 weeks. Because the premature infant liver is not fully developed at birth it may be incomplete the bilirubin metabolism. The purpose was to evaluate the metabolism and the excretion of bilirubin in the premature infant rat liver following prenatal glucocorticoid (GC) administration. Dexamethasone (DEX) was administered subcutaneously to pregnant Wistar rats for two consecutive days on gestational days 17 and 19. The fetus were delivered by cesarean section in gestational days 19 and 21. The mRNA levels and protein levels of bilirubin-metabolic enzymes and transporters in the fetal liver tissues were analyzed using RT-PCR immunohistochemistry staining and ELISA, respectively. We evaluated that the effect of bilirubin-metabolic enzymes in the primary fetal rat hepatocytes treated with DEX after pretreated with glucocorticoid receptor (GR, Nr3c1) and Pxr (Nr1i2) siRNA. Ugt1a1 and Bsep (Abcb11) mRNA levels were significantly increased in the fetuses by prenatal GC administration. The mRNA levels of nuclear transcription factors Nr1i2, Car (Nr1i3), and Rxrα (Nr2b1) were also significantly increased in the fetuses by prenatal GC administration. In addition, DEX increased Nr1i2, Ugt1a1, and Abcc2 (Mrp2) mRNA levels in the primary fetal hepatocytes. The Nr3c1 or Nr1i2 siRNA-mediated knockdown suppressed the increases of Ugt1a1, and Abcc2 mRNA levels induced by DEX, indicating that DEX are mediated by GC receptor and PXR in primary fetal hepatocytes. These results suggest that prenatal GC administration increases bilirubin-metabolic ability, in the premature liver, which may prevent jaundice in neonates.

FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression

ObjectiveMultidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated...