Elevated Serum Bilirubin Levels Research Articles

Triclosan administration to humanized UDP-glucuronosyltransferase 1 neonatal mice induces UGT1A1 through a dependence on PPARα and ATF4

Triclosan (TCS) is an antimicrobial toxicant found in a myriad of consumer products and has been detected in human tissues, including breastmilk. We have evaluated the impact of lactational TCS on UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and bilirubin metabolism in humanized UGT1 (hUGT1) neonatal mice. In hUGT1 mice, expression of the hepatic UGT1A1 gene is developmentally delayed resulting in elevated total serum bilirubin (TSB) levels. We found that newborn hUGT1 mice breastfed or orally treated with TCS presented lower TSB levels along with induction of hepatic UGT1A1. Lactational and oral treatment by gavage with TCS leads to the activation of hepatic nuclear receptors CAR, PPARα, and stress sensor, ATF4. When CAR-deficient hUGT1 mice (hUGT1/Car-/-) were treated with TCS, TSB levels were reduced with a robust induction of hepatic UGT1A1, leaving us to conclude that CAR is not tied to UGT1A1 induction. Alternatively, when PPARα-deficient hUGT1 mice (hUGT1/Pparα-/-) were treated with TCS, hepatic UGT1A1 was not induced. Additionally, we had previously demonstrated that TCS is a potent inducer of ATF4, a transcriptional factor linked to the integrated stress response. When ATF4 was deleted in liver of hUGT1 mice (hUGT1/Atf4ΔHep), and these mice treated with TCS, we observed superinduction of hepatic UGT1A1. Oxidative stress genes in livers of hUGT1/Atf4ΔHep treated with TCS were increased, suggesting that ATF4 protects liver from excessive oxidative stress. The increase oxidative stress may be associated with superinduction of UGT1A1. The expression of ATF4 in neonatal hUGT1 hepatic tissue may play a role in the developmental repression of UGT1A1.

Correlation between elevated serum bilirubin levels and coronary artery disease risk - An institutional study

Correlation between elevated serum bilirubin levels and coronary artery disease risk - An institutional study

Distinct bile acid alterations in response to a single administration of PFOA and PFDA in mice

Per- and polyfluoroalkyl substances (PFASs), a group of synthetic chemicals that were once widely used for industrial purposes and in consumer products, are widely found in the environment and in human blood due to their extraordinary resistance to degradation. Once inside the body, PFASs can activate nuclear receptors such as PPARα and CAR. The present study aimed to investigate the impact of perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) on liver structure and functions, as well as bile acid homeostasis in mice. A single administration of 0.1 mmole/kg of PFDA, not PFOA, elevated serum ALT and bilirubin levels and caused cholestasis in WT mice. PFDA increased total and various bile acid species in serum but decreased them in the liver. Furthermore, in mouse livers, PFDA, not PFOA, down-regulated mRNA expression of uptake transporters (Ntcp, Oatp1a1, 1a4, 1b2, and 2b1) but induced efflux transporters (Bcrp, Mdr2, and Mrp2–4). In addition, PFDA, not PFOA, decreased Cyp7a1, 7b1, 8b1, and 27a1 mRNA expression in mouse livers with concomitant hepatic accumulation of cholesterol. In contrast, in PPARα-null mice, PFDA did not increase serum ALT, bilirubin, or total bile acids, but produced prominent hepatosteatosis; and the observed PFDA-induced expression changes of transporters and Cyps in WT mice were largely attenuated or abolished. In CAR-null mice, the observed PFDA-induced bile acid alterations in WT mice were mostly sustained. These results indicate that, at the dose employed, PFDA has more negative effects than PFOA on liver function. PPARα appears to play a major role in mediating most of PFDA-induced effects, which were absent or attenuated in PPARα-null mice. Lack of PPARα, however, exacerbated hepatic steatosis. Our findings indicate separated roles of PPARα in mediating the adaptive responses to PFDA: protective against hepatosteatosis but exacerbating cholestasis.

Clinical Profile in Patients of Amoebic Liver Abscess with and without Hyperbilirubinemia: A Prospective Cohort Study

Introduction: In tropical countries like India, two-thirds of liver abscess cases are amoebic. Along with abdominal pain, fever, and other non-specific clinical features, jaundice is commonly observed in Amoebic Liver Abscess (ALA) cases. However, the understanding of jaundice in a patients with ALA is limited, and it is associated with a poor prognosis. Aim: To compare the morbidity and mortality of ALA patients with and without hyperbilirubinemia, as well as their clinical outcomes. Materials and Methods: The present prospective cohort study was conducted at a tertiary teaching institute in northern India. It included 150 patients aged between 20 and 60 years with a confirmed diagnosis of ALA. The patients were divided into two groups based on the presence or absence of hyperbilirubinemia. Those with jaundice resulting from other causes or a history of hepatitis were excluded. Variables examined in the study included age, sex, alcohol intake, basic laboratory parameters, ultrasound-assessed abscess size and number, and duration of hospital stay. Results: Among the 150 cases, 22 (14.6%) had elevated serum bilirubin levels (>1 mg/dL). Additionally, 122 (81.33%) had a history of alcohol intake, and 117 (78%) had a single abscess cavity. In ALA patients with hyperbilirubinemia, 12 (54.55%) had abnormal creatinine values, and 6 (27.26%) experienced complications such as rupture and peritonitis. One mortality occurred in a patient with ALA and jaundice. Conclusion: ALA patients with jaundice exhibited larger abscess cavities, a higher complication rates, a longer hospital stays, and a poor prognoses.

Clinical Implications of Serum Bilirubin and Procalcitonin in the Diagnosis of Acute Appendicitis

Acute appendicitis remains a common surgical emergency with challenges in prompt and accurate diagnosis. Serum biomarkers have garnered attention for their potential role in aiding diagnostic accuracy. This paper aims to update the clinical implications of serum bilirubin and procalcitonin levels in diagnosing acute appendicitis. A systematic review of literature was conducted, encompassing studies that investigated the relationship between serum bilirubin and procalcitonin levels and acute appendicitis. The search strategy included electronic databases, resulting in a comprehensive analysis of relevant articles. The findings suggest a notable association between elevated serum bilirubin levels and the presence of acute appendicitis. Furthermore, procalcitonin exhibited promising diagnostic potential, demonstrating a significant correlation with the severity of appendicitis. Subgroup analyses revealed varied sensitivity and specificity values, indicating the need for further refinement in clinical application. The integration of serum biomarkers, specifically bilirubin and procalcitonin, into the diagnostic algorithms of acute appendicitis could potentially enhance the accuracy of clinical assessments. However, limitations in existing studies, such as heterogeneity in patient populations and differing assay methodologies, emphasize the necessity for standardized protocols and larger prospective trials. In conclusion, serum bilirubin and procalcitonin levels show promise as adjunctive tools in diagnosing acute appendicitis. Their incorporation into clinical practice warrants careful consideration and validation through larger-scale studies to delineate their precise diagnostic utility, thereby potentially optimizing patient care pathways in the context of this prevalent surgical condition. Keywords : Acute appendicitis, Bilirubin, Procalcitonin, Diagnosis, Clinical implications

A fetal wound healing program after intrauterine bile duct injury may contribute to biliary atresia

Biliary atresia (BA) is an obstructive cholangiopathy that initially affects the extrahepatic bile ducts (EHBDs) of neonates. The etiology is uncertain, but evidence points to a prenatal cause. Fetal tissues have increased levels of hyaluronic acid (HA), which plays an integral role in fetal wound healing. The objective of this study was to determine whether a program of fetal wound healing is part of the response to fetal EHBD injury. Mouse, rat, sheep, and human EHBD samples were studied at different developmental time points. Models included a fetal sheep model of prenatal hypoxia, human BA EHBD remnants and liver samples taken at the time of the Kasai procedure, EHBDs isolated from neonatal rats and mice, and spheroids and other models generated from primary neonatal mouse cholangiocytes. A wide layer of high molecular weight HA encircling the lumen was characteristic of the normal perinatal but not adult EHBD. This layer, which was surrounded by collagen, expanded in injured ducts in parallel with extensive peribiliary gland hyperplasia, increased mucus production and elevated serum bilirubin levels. BA EHBD remnants similarly showed increased HA centered around ductular structures compared with age-appropriate controls. High molecular weight HA typical of the fetal/neonatal ducts caused increased cholangiocyte spheroid growth, whereas low molecular weight HA induced abnormal epithelial morphology; low molecular weight HA caused matrix swelling in a bile duct-on-a-chip device. The fetal/neonatal EHBD, including in human EHBD remnants from Kasai surgeries, demonstrated an injury response with prolonged high levels of HA typical of fetal wound healing. The expanded peri-luminal HA layer may swell and lead to elevated bilirubin levels and obstruction of the EHBD. Biliary atresia is a pediatric cholangiopathy associated with high morbidity and mortality rates; although multiple etiologies have been proposed, the fetal response to bile duct damage is largely unknown. This study explores the fetal pathogenesis after extrahepatic bile duct damage, thereby opening a completely new avenue to study therapeutic targets in the context of biliary atresia.

270 The Liberal Use of Magnetic Resonance Cholangiopancreatography (MRCP) can be switched over to its Selective use to detect choledocholithiasis

Abstract Background Gallstone disease is known in 10-15% of adults in Western populations. Cholangiopancreatography is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well-defined. The NICE guidelines recommend MRCP be done when common bile duct dilatation ≥ 8mm or liver function tests) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualized basis. Due to these reasons, MRCP is at times done unnecessarily which creates an economic burden and restricts access to patients in real need of imaging slots. Method It is a hospital-based retrospective observational study. The time frame was July 2021 to July 2022. The sample size was 230 patients. Result Our Study showed that isolated elevated Alanine Aminotransferase levels should not be a reason to evaluate patients for Choledocholithiasis. It concluded that elevated serum bilirubin levels, Alkaline Phosphatase, and Gamma Glutamyl Transferase are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Hepatitis B induced fulminant liver failure: A call for prevention

Acute fulminant hepatic failure is a condition in which a healthy liver deteriorates rapidly following an insult, resulting in the impairment of its synthetic functions. This condition is rare and is associated with high fatality rates. We report the case of a 19-year-old male who was brought to the emergency room in an unconscious state with jaundice and persistent fever for 2–3 weeks after recently commencing intravenous use of morphine. He was found to be hepatitis B surface antigen reactive, and his laboratory tests indicated severe liver dysfunction with elevated levels of serum bilirubin, aspartate transaminase, alanine transaminase, gamma-glutamyl transferase, and International normalized ratio. The patient was diagnosed with fulminant liver failure with coagulopathy and hepatic encephalopathy. The patient’s family was addressed and counseled regarding the urgent need for liver transplantation. However, due to a lack of funds and insurance, supportive treatment was the only option left. Despite all supportive measures, the patient expired within 48 h. This case highlights the importance of various socioeconomic issues involved with liver transplantation, as in a resource-limited setting, urgent transplantation seems nearly impossible. In addition, this case report raises certain ethical issues that need consideration, particularly in an injection drug use scenario. It also highlights the importance of addressing the rising issue of injection drug use among youth, particularly in the regions of Punjab.

Hierarchical decision model for in vitro bilirubin content prediction from absorption spectrum of whole blood.

Bilirubin forms by the breakdown of heme proteins in the liver, but a newborn's sluggish liver can lead to elevated serum bilirubin levels that cross the blood-brain barrier and result in kernicterus. Earlier studies have used the 400 to 500nm optical wavelength range to characterize the bilirubin content. There is not a universally established correlation among other wavelengths and the amount of bilirubin in clinical whole blood samples. We demonstrated that the amount of bilirubin could be quantified with accuracy in a label-free, self-referenced manner using only a few wavelengths, viz. 468, 492, 500, 560, 605, 645, 660, and 675nm, wherein band-averaged absorption measurements are used. We addressed the above problem by conducting a preliminary study containing 50 neonates through an absorption spectrum measurement of whole blood in 3 to samples from the neonates. We constructed a hierarchical decision method that first grossly divides the 30 neonates of the training set into and bilirubin level cohorts. A subsequent boundary condition further divides the group into two and bilirubin level cohorts. A finer measure later predicted the bilirubin content of each of these groups as low (), medium (10 to ), and high (). Using this hierarchical decision model statistical approach, we quantified the amount of bilirubin in the 20 testing set samples with 82% accuracy. We formulated a biostatistical model in which we automated the spectrometric determination of total bilirubin in the whole blood for patients of neonatal hyperbilirubinemia.

The liberal use of magnetic resonance cholangiopancreatography can be switched over to its selective use to detect choledocholithiasis

Background: Gallstone disease is known in 10-15% of adults in Western populations. Magnetic resonance cholangiopancreatography (MRCP) is the investigation of choice for choledocholithiasis; however, its use is varied, and guidelines are not well defined. The National Institute for Health and Care (NICE) guidelines recommends MRCP to be done when common bile duct (CBD) dilatation ≥8 mm or liver function tests (LFTs) are abnormal but do not quantify this further. The liberal use of MRCP is gaining popularity as a roadmap prior to cholecystectomy, aiming to assess primarily for the presence of migrated gallstones within the cystic duct or common bile duct, as well as providing information regarding the anatomical features of the extrahepatic biliary tree on an individualised basis. Due to these reasons MRCP at times is done unnecessarily which creates economic burden and restricts access to patients in real need of imaging slots. Methods: It is hospital based retrospective observational study. Time frame was July 2021 to July 2022 and sample size was 230 patients. Results: Our study showed that isolated elevated alanine aminotransferase (ALT) level should not be reason to evaluate patients for choledocholithiasis. It concluded that elevated serum bilirubin levels, alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Conclusions: To conclude elevated serum bilirubin levels, ALP and GGT are the strongest predictors of CBD stones in patients with gallstone disease and hence can be used to triage patients for undergoing MRCP. Isolated elevated ALT should not be a reason to evaluate patients for CBD stones.

Association Between Serum Bilirubin and Atrial Fibrillation: A Mendelian Randomization Study.

The association between bilirubin and atrial fibrillation (AF) has been evaluated previously in observational studies but with contradictory results. This study evaluated the causal association between serum bilirubin level and AF using Mendelian randomization (MR) analysis. This cross-sectional study includes 8,977 participants from the Dong-gu Study. In the observational analysis, multivariate logistic regression was performed to evaluate the association between bilirubin and prevalent AF. To evaluate the causal association between bilirubin and AF, MR analysis was conducted by using the UGT1A1 rs11891311 and rs4148323 polymorphisms as instrumental variables. Elevated serum bilirubin levels were associated with an increased risk for AF in observational analysis (total bilirubin: odds ratio [OR], 1.31; 95% confidence interval [95% CI], 1.15-1.48 per 1 standard deviation [SD]; direct bilirubin: OR, 1.31; 95% CI, 1.18-1.46 per 1 SD), whereas the genetically predicted serum bilirubin levels in MR analysis did not show this association (total bilirubin: OR, 1.02; 95% CI, 0.67-1.53 per 1 SD; direct bilirubin: OR, 1.03; 95% CI, 0.61-1.73 per 1 SD). Genetically predicted bilirubin levels were not associated with prevalent AF. Thus, the observational association between serum bilirubin levels and AF may be non-causal and affected by reverse causality or unmeasured confounding.

Neonatal Jaundice: Knowledge, Practice, And Attitudes Among Primigravida Women

ABSTRACT Objective: Neonatal jaundice is characterized by a yellowish coloration of the skin and sclera of newborn infants and elevated serum bilirubin levels. In this study, it was aimed to evaluate the knowledge, practices and attitudes of primigravidas in Diyala province of Iraq regarding neonatal jaundice. Material and Methods: A questionnaire was applied to 165 women who were primigravidas between January 1, 2022 and March 31, 2022 in hospitals and health centers to evaluate their knowledge, practices and attitudes about neonatal jaundice. Results: Although 71.4% of the women knew the two signs of neonatal jaundice, 78.8% of them did not know any of the dangerous signs of neonatal jaundice. 28.4% of women knew that there are two effective treatment methods for the treatment of neonatal jaundice. 57.6% of the women were not aware of any of the severe complications of neonatal jaundice. Conclusion: Most of the primigravida in this study decided to visit physicians when their babies have jaundice without using traditional treatment.

Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis.

Oxidative stress and inflammation contribute significantly to atherogenesis. We and others have demonstrated that mildly elevated serum bilirubin levels protect against coronary and peripheral atherosclerosis, most likely due to the antioxidant and anti-inflammatory activities of bilirubin. The aim of the present study was to assess serum bilirubin and the markers of oxidative stress and inflammation in both healthy subjects and patients with various forms of atherosclerosis. The study was performed in patients with premature myocardial infarction (n = 129), chronic ischemic heart disease (n = 43), peripheral artery disease (PAD, n = 69), and healthy subjects (n = 225). In all subjects, standard serum biochemistry, UGT1A1 genotypes, total antioxidant status (TAS), and concentrations of various pro- and anti-inflammatory chemokines were determined. Compared to controls, all atherosclerotic groups had significantly lower serum bilirubin and TAS, while having much higher serum high-sensitivity C-reactive protein (hsCRP) and most of the analyzed proinflammatory cytokines (p < 0.05 for all comparisons). Surprisingly, the highest inflammation, and the lowest antioxidant status, together with the lowest serum bilirubin, was observed in PAD patients, and not in premature atherosclerosis. In conclusion, elevated serum bilirubin is positively correlated with TAS, and negatively related to inflammatory markers. Compared to healthy subjects, patients with atherosclerosis have a much higher degree of oxidative stress and inflammation.

S3177 The (Icteric) Eye of the Storm: A Case of Weil’s Syndrome

Introduction: Leptospirosis is one of the most prevalent zoonotic diseases affecting humans residing in tropical areas. We herein describe a case of a patient with leptospirosis acquired in the Bronx, NY. Case Description/Methods: A 63 year-old man with no significant medical history was evaluated for muscle pain, fatigue, and diarrhea of 3 days duration. He was feverish to 102 F and icteric. Laboratory evaluation revealed hemoglobin of 7.5 g/dL, total white count of 18 k/uL, platelet count of 40 k/uL, INR 1.5, creatinine of 5 mg/dL, urea nitrogen 85 mg/dL, creatine kinase 4000 U/L, alkaline phosphatase 192 U/L, total bilirubin 39 mg/dL, direct bilirubin > 23 mg/dL, AST 96 U/L, ALT 113 U/L and albumin 2.5 g/dL. Initial laboratory evaluation was negative for common and atypical infections. Radiologic evaluation revealed unremarkable non-contrast MRCP and US abdomen. Upon further detailed history, the patient reported that his basement was recently flooded by a devastating hurricane. Despite negative parasite blood smear and IgM antibodies for leptospira, empiric treatment for leptospirosis with Ceftriaxone resulted in resolution of all symptoms and lab abnormalities. Repeated blood work on follow-up visits at 4 weeks was noted with positive IgM antibodies for leptospira (Figure). Discussion: Leptospirosis is caused by a poorly staining gram-negative spirochetal bacteria. Transmission to humans occurs through mucous membranes, open skin wounds or after drinking, eating, swimming, or wading in water contaminated by stool or urine of infected rodents. Outbreaks have been documented in non tropical, urban areas affected by hurricanes, heavy rains or floods. In approximately 90% of cases, the disease is anicteric. Phase 1 includes viral-like illness, conjunctival suppuration followed by transient improvement. Phase 2 includes myalgia, nausea, vomiting, abdominal pain, hepatomegaly, increased serum bilirubin and serum aminotransferases. 10% of cases manifest as Weil’s syndrome, characterized by jaundice in the first phase, followed by second phase manifesting with high fever, profound jaundice with severely elevated serum bilirubin levels (up to 30mg/dL, mostly direct) and elevated serum transaminases. Renal and liver involvement are predominant and can lead to severe morbidity and death. Blood cultures, urine cultures and specific anti Leptospira IgM serology can assist with diagnosis. Antibiotic treatments, primarily Penicillin, 3rd generation Cephalosporins and Doxycycline, can benefit if administered at an early stage.Figure 1.: Laboratory evaluation during hospital stay and 4 weeks after discharge. Abbreviation: ALP, alkaline phosphatase; TB, total bilirubin; DB, direct bilirubin; AST, Aspartate transaminase; ALT, Alanine transaminase.

Determinants of neonatal jaundice in Ethiopia: a systematic review and meta-analysis

Neonatal jaundice is a common condition characterized by a yellowish discoloration of the skin, conjunctiva, and sclera caused by elevated serum or plasma bilirubin levels during the newborn period. The condition is usually not dangerous, but it can progress to severe hyperbilirubinemia, which can lead to acute bilirubin encephalopathy and kernicterus, a bilirubin-induced neurological damage. Therefore, this study aimed to assess the pooled prevalence of neonatal jaundice and its determinants in Ethiopia. Scopus, PubMed, Google Scholar, Embase, and CINAHL databases were searched for studies published between January 1, 2010 and July 30, 2021. A weighted DerSimonian Laird random-effects model was used to estimate the pooled prevalence of neonatal jaundice and its associated factors. The I2 was used to calculate the degree of heterogeneity. The funnel plot and Egger's regression test were used to assess publication bias. Totally 697 articles were generated from various databases, and the review included a total of eight articles. The pooled prevalence of neonatal jaundice was 30.96% [95% confidence interval (CI) 16.61%-45.31%)] in Ethiopia. This review showed that prolonged labor [adjusted odd ratio (AOR) = 3.39; 95% CI 2.41-4.77), low birth weight (AOR = 5.12; 95% CI 3.11-8.72), birth asphyxia (AOR = 3.75; 95% CI 2.11-6.66), cephalohematoma (AOR = 7.07; 95% CI 2.72-18.38), ABO incompatibility (AOR = 6.05; 95% CI 2.95-12.42), Rhesus (RH) incompatibility (AOR = 3.77; 95% CI 2.04-6.96), male sex (AOR = 4.53; 95% CI 3.39-6.07), and neonatal sepsis (AOR = 2.47; 95% CI 1.49-4.08) were identified as a determining factor for neonatal jaundice in Ethiopia. In low- and middle-income countries, neonatal jaundice is a significant healthcare burden, accounting for a significant portion of global childhood mortality and morbidity. However, some low-cost, effective, practical, and dependable solutions have been implemented. Prolonged labor, ABO incompatibility, RH incompatibility, birth asphyxia, neonatal sepsis, low birth weight, cephalohematoma, and male sex were identified as risk factors for neonatal jaundice in Ethiopia.

Long-Term Follow-Up into Adulthood of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Sclerosing Cholangitis.

We reviewed records of patients followed for PSC or AIC between 1998 and 2019 at a pediatric referral center. Features at diagnosis, biochemical and liver-related outcomes (cholangitis, liver transplant, and cirrhosis) were compared. Forty patients (27 PSC, 13 AIC) were followed for 92 months on average (standard deviation 79 months) with extension into adulthood in 52.5%; 70% had associated inflammatory bowel disease (IBD). The proportion of patients with significant fibrosis and abnormal baseline liver tests (serum bilirubin and transaminase levels) were similar in both groups. One year postdiagnosis, 55% (15/27) of PSC patients had normal liver tests versus only 15% (2/13) in the AIC group (P = 0.02). During follow-up, more liver-related events occurred in the AIC group (69% versus 27%, hazard ratio [HR] = 3.7 [95% confidence interval (CI): 1.4-10] P = 0.01). Baseline elevated serum bilirubin levels (HR = 5.3 [95% CI: 1.7-16.9] P = 0.005) and elevated transaminase levels at 1 year (HR = 9.09 [95% CI: 1.18-66.7) P = 0.03) were predictive of liver-related events, while having IBD was not (HR = 0.48 (95% CI: 0.15-1.5) P = 0.22). Pediatric patients with AIC and PSC presented at a similar fibrosis stage, however, with a more severe hepatitis in AIC. In this cohort, AIC was associated with more liver-related events, primarily driven by a higher rate of cirrhosis compared with PSC; transplant rates were similar.

THU196 - Elevated serum bilirubin levels and aminotransferases are associated with immuno-modulatory and suppressive subsets in pregnant females with intrahepatic cholestasis and hepatitis E virus infection

THU196 - Elevated serum bilirubin levels and aminotransferases are associated with immuno-modulatory and suppressive subsets in pregnant females with intrahepatic cholestasis and hepatitis E virus infection

Increase of HO-1 Expression in Critically Ill COVID-19 Patients Is Associated with Poor Prognosis and Outcome.

Heme-oxygenase (HO)-1 is a cytoprotective enzyme with strong antioxidant and anti-apoptotic properties and previous reports have also emphasized the antiviral properties of HO-1, either directly or via induction of interferons. To investigate the potential role of HO-1 in patients with coronavirus disease 2019 (COVID-19), the present study assessed changes in HO-1 expression in whole blood and tissue samples. Upregulation of HO-1 protein was observed in lung, liver, and skin tissue independently of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence. A significant increase of blood HO-1 mRNA levels was observed in critically ill COVID-19 patients compared to those in severe COVID-19 patients and healthy controls. This increase was accompanied by significantly elevated levels of serum ferritin and bilirubin in critically ill compared to patients with severe disease. Further grouping of patients in survivors and non-survivors revealed a significant increase of blood HO-1 mRNA levels in the later. Receiver operating characteristic (ROC) analysis for prediction of ICU admission and mortality yielded an AUC of 0.705 (p = 0.016) and 0.789 (p = 0.007) respectively indicating that HO-1 increase is associated with poor COVID-19 progression and outcome. The increase in HO-1 expression observed in critically ill COVID-19 patients could serve as a mechanism to counteract increased heme levels driving coagulation and thrombosis or as an induced protective mechanism.

Gilbert Syndrome and Genetic Findings in Children: A Tertiary-Center Experience from Turkey.

ObjectiveGilbert syndrome (GS) is a disease characterized by mildly elevated indirect serum bilirubin levels due to mutation in the promoter of the UGT1A1 gene, which causes a decrease in uridine diphosphate glucuronyltransferase enzyme activity. Gilbert syndrome should be considered based on clinical and laboratory findings in differential diagnosis, which can be supported by genetic analysis. This study aimed to evaluate the clinical findings and UGT1A1 mutations of children with Gilbert syndrome.Materials and MethodsPatients who were admitted to the pediatric gastroenterology clinic and who were considered to have Gilbert syndrome based on clinical and laboratory findings were included in the study. The UGT1A1 analysis was performed by Sanger sequence analysis.ResultsA total of 56 children were included in the study. A(TA)7TAA, A(TA)6TAA, and (TA)6/7 allele promoter polymorphism was detected in 75.5%, 22.5%, and 2% of the patients, respectively. Other than these, in 3 patients, 3 different sequence variants associated with GS [c.880_893delinsA (p.Tyr294MetfsTer69) and c.1091C>T(p.Pro365Leu)] were detected.ConclusionWe detected 7 TA repeats in the majority of our patients. A mild bilirubin elevation was determined in cases with 6 repetitions that were not considered risky for Gilbert syndrome. We concluded that the c.880_893delinsA (p.Tyr294MetfsTer69) variant, previously shown to be associated with Crigler–Najjar syndrome type I, may also be associated with partial enzyme deficiency leading to the Gilbert syndrome phenotype.

Treatment practices and implementation of guidelines for hyperbilirubinemia and rebound hyperbilirubinemia.

Hyperbilirubinemia (HB), defined as elevated total serum bilirubin (TSB) levels, commonly affects neonates and requires prompt treatment to prevent neurological complications. Up to 10%of neonates experience rebound hyperbilirubinemia (RHB), requiring re-initiation of treatment. Unfortunately, treatment guidelines lack practical recommendations surrounding subthreshold phototherapy, treatment termination, and RHB investigations. We examined local management practices for HB and RHB treatment in a well newborn nursery. As a secondary aim, we investigated the association between treatment practices and RHB rates. Retrospective chart review identified neonates treated for hyperbilirubinemia between January 2015 and December 2019 during their birth hospitalization at a tertiary care centre. Standardized data collection sheets were used to record treatment parameters. Over the 5-year period, there were 9683 births and 305 (3.15%) neonates received phototherapy. Of the treated cases, 20-25%were subthreshold to practice guideline values. Upon treatment termination 25-55%of cases had TSB levels within 3 mg/dL, which may increase the risk of RHB. In our cohort, 20.3%of treated cases experienced one episode of RHB and 3.9%experienced two episodes of RHB. Although clinicians evaluated neonates for RHB 0-12 hours following treatment termination prior to discharge, many cases were identified in outpatient settings and required re-admission for phototherapy. When managing HB and RHB, treatment practices such as when to terminate treatment in relation to threshold values, and timing of RHB investigations, are largely inconsistent amongst clinicians. Future studies are required to better understand the landscape of hyperbilirubinemia treatment beyond initiation of phototherapy.