Hyperbilirubinemia In Patients Research Articles

ASSOCIATION BETWEEN ACUTE APPENDICITIS AND HYPERBILIRUBINEMIA

Background: Acute appendicitis is one of the most common causes of acute abdomen requiring emergency surgical intervention. Complicated appendicitis, such as gangrene or perforation, significantly increases morbidity and mortality. Early diagnosis is crucial to improving outcomes, but no single diagnostic test is definitive. Hyperbilirubinemia has recently emerged as a potential biomarker for acute appendicitis, particularly in complicated cases. Evaluating its diagnostic accuracy can aid in the timely management of this condition, especially when integrated with clinical and laboratory assessments. Objective: To study the association and diagnostic accuracy of hyperbilirubinemia in patients presenting with acute appendicitis. Methods: This prospective observational study was conducted at the Department of Surgery, Combined Military Hospital Sialkot, from September 2023 to July 2024. A total of 163 patients aged 12-60 years with a clinical diagnosis of acute appendicitis, who underwent appendectomy, were included. Pre-operative serum bilirubin levels were analyzed to determine their association with acute appendicitis. Post-operative histopathological examination served as the gold standard for diagnosis. Data on demographics, clinical presentation, and laboratory findings were collected and analyzed using descriptive and diagnostic statistics, including sensitivity, specificity, positive predictive value, and negative predictive value. Results: Of the 163 patients, 103 (63.2%) were male and 60 (36.8%) were female, with a male-to-female ratio of 1.7:1. The mean age was 27.47 ± 11.33 years. Hyperbilirubinemia was detected in 114 (69.1%) patients, of which 111 (97.4%) were true positives and 3 (2.6%) were false positives. Among patients with acute appendicitis, 78 (70.2%) had uncomplicated appendicitis, while 33 (29.85%) had complicated appendicitis (gangrene or perforation). Hyperbilirubinemia demonstrated a sensitivity of 78.17%, specificity of 85.71%, positive predictive value of 97.37%, negative predictive value of 36.73%, and diagnostic accuracy of 79.14%. Conclusion: Hyperbilirubinemia showed a significant association with acute appendicitis, particularly in complicated cases. Its diagnostic accuracy suggests it can serve as a valuable pre-operative adjunctive marker, enhancing the timely diagnosis and management of acute appendicitis.

The association of oxidative stress of neonatal hyperbilirubinemia and vitamin E supplementation.

Jaundice in newborns is a sign of skin and sclera pigmentation. Hyperbilirubinemia and these phenomena do, however, have a relationship. According to many clinical studies, elevated blood bilirubin and low vitamin E (VE) levels in newborns are associated. The aim of the study was to investigate the association of oxidative stress of neonatal hyperbilirubinemia in patients who underwent phototherapy with additional vitamin E supplementation (25 mg/kg/day over the course of three days) and patients without additional vitamin E. A set of 100 neonatal indirect hyperbilirubinemia patients was enrolled at neonatal intensive care units (NICUs) of the pediatric departments at Al Azhar University Hospitals during the period from February 2021 to October 2022 after obtaining signed written informed consent of all neonates' parents with an explanation of the aim of study. Significant differences were found between the studied groups regarding serum bilirubin on the third day of admission (p = 0.039). Patients who were treated with vitamin E had lower serum bilirubin on the third day of admission (8.25 ±3.41) than the control group (11.66 ±3.22). Also, among the VE group, serum bilirubin was significantly decreased on the third day of admission (8.25 ±3.41) compared to zero days of admission (14.10 ±4.39) (p = 0.041). Vitamin E supplementation has an important role in treatment of indirect hyperbilirubinemia in neonates. Early administration of vitamin E in preterm neonates resulted in a significant decrease of serum bilirubin and increased total antioxidant capacity. Vitamin E supplementation in full term decreased the duration of phototherapy.

Continuous glucose monitoring parameters in pregnancy-related complications in patients with type 1 diabetes: a retrospective cohort study.

Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). The primary study objective was to analyze associations between numerous novel CGM parameters and neonatal complications, such as large‑for‑gestational‑age (LGA) neonates, hypoglycemia, hyperbilirubinemia, transient breathing disorders, preterm births, as well as pre‑eclampsia. In this single‑center retrospective cohort study, we recruited 102 eligible pregnant women with T1D who were treated with sensor‑augmented pumps with suspend‑before‑low function from the first trimester. The pregnant patients were admitted for at least 1 control hospital visit in each trimester of gestation for anthropometric and laboratory measurements and collection of sensor data. The median (interquartile range) percentage values for glycated hemoglobin (HbA1c) (first trimester, 6.23 [5.91-6.9]; second trimester, 5.49 [5.16-5.9]; third trimester, 5.75 [5.39-6.29]) and for time‑in‑range (first trimester, 72.4 [67.3-80.3]; second trimester, 72.5 [64.7-79.6]; third trimester, 75.9 [67.1-81.4] met the criteria of well‑controlled T1D in each trimester of pregnancy. Nonetheless, we noted 27% of LGA births, 25% of neonatal hypoglycemia, 33% of hyperbilirubinemia, and 13% of preterm births. Worse glycemic control and more glycemic fluctuations in the second and third trimesters were mainly associated with increased risk of LGA at birth, transient breathing disorders, and hyperbilirubinemia. CGM parameters (mean of daily differences, high blood glucose index, glycemic risk assessment in diabetes equation, or continuous overall net glycemic action) in the patients with T1D are significantly associated with the increased risk of LGA at birth and neonatal transient breathing disorders and hyperbilirubinemia. However, we did not find evidence that novel CGM indices could be more effective in predicting those events than the commonly used CGM parameters or HbA1c levels.

Frequency of Hyperbilirubinemia in Perforated Appendicitis - A Current Update on Diagnostics and Management.

Background: Perforated appendix can be detected earlier by chemically with the aid of hyperbilirubinemia. It is a simple non-invasive modality that can aid to detecting complicated appendicitis and avoid morbidity. Aim: To assess frequency of hyperbilirubinemia in patients undergoing appendectomy due to perforated appendicitis. Methods: A descriptive cross-sectional study was conducted in which a total of 75 patients undergoing emergency appendectomy due to perforated appendicitis and age 15-70 years were recruited. Patients with CLD, pregnancy, Congenital or acquired biliary disease, alcoholism and hemolytic disease were excluded. Blood sample was obtained and was sent to the hospital histopathology laboratory and it was reported by consultant pathologist for assessment of hyperbilirubinemia. Results: Age range in this study was from 15-70 years with mean age of 30.69±14.37 years. Majority of the patients 56(74.67%) were 15-40 years of age. Out of these 75 patients, 43(57.33%) were male and 32(42.67%) were females. Mean hyperbilirubinemia was 1.67±0.87 mg/dl. Frequency of hyperbilirubinemia in patients undergoing appendectomy due to perforated appendicitis was found in 63 (84.0%) patients. Practical implication: This will aid in prompt diagnosis and early management of perforated appendix, and serum bilirubin can be used as modality for diagnosis in the absence of ultrasound facility. Conclusion: Frequency of hyperbilirubinemia in patients undergoing appendectomy due to perforated appendicitis is very high. Keywords: perforated appendicitis, hyperbilirubinemia, appendectomy, bilirubin level, perforation, sensitivity.

Evaluation of the influence of methods of sanitation of the common bile duct on the course of the postoperative period of endoscopic papillosphincterotomy

Gallstone disease continues to occupy a leading position in terms of the number of surgical interventions in modern emergency surgery. The purpose of our study is to determine the risks of developing post-manipulation pancreatitis depending on the method of sanitation of the choledochus, to determine the dynamics of regression of hyperamylasemia and hyperbilirubinemia in patients after endoscopic papillosphincterotomy (EPST), to assess long-term results—the frequency of repeated hospitalizations and the need to perform surgical interventions for restenosis of the papilla. Materials and methods : a prospective analysis of 60 clinical cases of patients after EPST was performed. Patients were divided into 2 groups depending on the method of sanation of the common choledochus. The frequency of development of an increase in the level of blood amylase and bilirubin and the timing of regression of these indicators were assessed. An analysis was also made of repeated cases of hospitalizations and the need for interventions on the papilla. Results : the development of hyperamylasemia in the group of revision of the choledochus occurred in 23% of cases, in the group without mechanical sanitation — in 13%. Hyperbilirubinemia in the immediate postoperative period developed in 27 and 23% of cases, respectively. The terms of regression of elevated biochemical parameters were higher in the group of patients with a mechanical method of sanation of the common choledochus. Conclusion : mechanical methods of sanation of the common choledochus can increase the incidence of post-manipulation complications after EPST and increase the recovery time for normal values of biochemical parameters. To assess the longterm results of the development of papillary restonosis after EPST, it is necessary to form larger groups of patients with the possibility of conducting a multicenter study.

Risk factors analysis of hyperbilirubinemia after off-pump coronary artery bypass grafting: a retrospective observational study

BackgroundHyperbilirubinemia is a common complication after off-pump coronary artery bypass grafting (OPCAB), but the incidence and the risk factors are unclear. This study aimed to analyze the incidence and risk factors of postoperative hyperbilirubinemia in patients undergoing OPCAB.MethodsFrom December 2016 to March 2019, a total of 416 consecutive patients undergoing OPCAB were enrolled in this single-center retrospective study. Patients were divided into the normal serum total bilirubin group and the hyperbilirubinemia group based on the serum total bilirubin levels. Perioperative variables between the two groups were compared by univariate logistic regression analysis. Then, multivariate binary logistic regression analysis was used to analyze the independent risk factors of developing hyperbilirubinemia in patients underwent OPCAB. P < 0.05 was considered as statistically significant.ResultsThirty two of 416 (7.7%) patients developed postoperative hyperbilirubinemia. Univariate regression analysis showed significant differences in gender (73.96% vs. 93.75%, P = 0.012), preoperative total bilirubin levels (11.92 ± 4.52 vs. 18.28 ± 7.57, P < 0.001), perioperative IABP implantation (22.66% vs. 43.75%, P = 0.008), perioperative blood transfusion (37.50% vs. 56.25%, P = 0.037) between the two groups. Multivariate logistic regression analysis revealed that elevated preoperative serum total bilirubin levels (OR = 1.225, 95% CI 1.145–1.310, P < 0.001), perioperative blood transfusion (OR = 4.488, 95% CI 1.876–10.737, P = 0.001) and perioperative IABP implantation (OR = 4.016, 95% CI 1.709–9.439, P = 0.001) were independent risk factors for hyperbilirubinemia after OPCAB.ConclusionsHyperbilirubinemia is also a common complication after OPCAB. Elevated preoperative serum total bilirubin levels, perioperative blood transfusion, and perioperative IABP implantation were independent risk factors for patients developing hyperbilirubinemia after OPCAB. Further studies need to be conducted to confirm the risk factors of hyperbilirubinemia after OPCAB procedure.

Bilirubin adsorption versus plasma exchange for hyperbilirubinemia in patients after cardiac surgery: a retrospective study

ObjectiveHyperbilirubinemia after cardiac surgery increases in-hospital mortality and is associated with poor prognosis. Our present study aimed to compare the efficacy of bilirubin adsorption (BA) and plasma exchange (PEX) in patients with hyperbilirubinemia after cardiac surgery.MethodsWe retrospectively included patients who underwent BA treatment or PEX treatment due to severe hyperbilirubinemia after cardiac surgery at our center from 2015 to 2020. We collected results from urine and liver function tests before and after treatment and compared the in-hospital mortality and morbidity between the two treatment groups.ResultsA total of 56 patients were enrolled in this study: 14 patients received BA treatment, and 42 patients received PEX treatment. Compared to the PEX group, the BA group exhibited a statistically significant reduction in total bilirubin (p = 0.016) and direct bilirubin (p = 0.036) levels. The in-hospital mortality was 85.7% (48/56) in the whole group, and the BA group had a lower mortality than the PEX group (71.4% vs. 90.5%, p = 0.078). The BA group showed better circulatory support, including lower risks of IABP (21.4% vs. 52.4%, p = 0.044), ECMO (21.4% vs. 50.0%, p = 0.061), reintubation (64.3% vs. 40.5%, p = 0.122) and ventricular arrhythmias (64.3% vs. 45.2%, p = 0.217). The in-hospital mortality was still lower in the BA treatment group than in the PEX treatment group (71.4% vs. 100%, p = 0.049) in the matched cohort.ConclusionsCompared to PEX treatment, BA treatment had a higher bilirubin removal ability in patients with hyperbilirubinemia and could reduce the mortality and risks of poor clinical outcomes. BA treatment should be considered an effective treatment method for patients with higher total bilirubin or direct bilirubin levels.

Influence of UGT1A1 promoter polymorphism, α-thalassemia and βs haplotype in bilirubin levels and cholelithiasis in a large sickle cell anemia cohort.

Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and βS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and βS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with βS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.

Precipitating factors causing hyperbilirubinemia during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir.

Hepatic decompensation is a fatal on-treatment side effect during chronic hepatitis C treatment with paritaprevir/ritonavir/ombitasvir and dasabuvir (PrOD). Prompt bilirubin testing can reveal hepatic failure in susceptible patients, and clinical parameters precipitating early elevation of bilirubin can warn clinicians to avoid PrOD prescription. This retrospective study included 169 Hepatitis C virus (HCV)-genotype 1b patients who underwent a 12-week course of PrOD with or without ribavirin. Laboratory data underwent χ analysis with Fisher's exact test to determine the precipitating factors causing hyperbilirubinemia in patients who had received 1 week of treatment. Sustained viral response was achieved in 164 patients (97.0%). Total bilirubin was ≥2 mg/dL (21.3%) in 36 patients after 1 week of treatment. Pretreatment white blood cell (WBC) <4500/µL and platelet <100,000/µL correlated with total bilirubin ≥2 mg/dL (relative risk [RR]: 21.64, 95% CI: 5.23-89.64, p < 0.001) after 1 week of treatment. Pretreatment platelet ≥100 000/µL and WBC <4500/µL correlated with direct bilirubin ≥0.45 mg/dL (RR: 6.56, 95% CI: 1.42-30.38, p = 0.016) and indirect bilirubin ≥0.6 mg/dL (RR: 4.77, 95% CI: 1.03-22.15, p = 0.046). Pretreatment platelet <100,000/µL with F3/F4 fibrosis correlated with first week total bilirubin ≥2 mg/dL (RR: 3.57, 95% CI: 1.35-9.09, p = 0.010). PrOD is an effective antiviral regimen for HCV genotype 1b patients. Total bilirubin ≥2 mg/dL after 1 week of treatment serves as an early warning of irreversible progression toward hepatic decompensation, and the current study provides a guide by which to monitor chronic hepatitis C patients undergoing PrOD treatment.

S2627 A Case of K2-Induced Hyperbilirubinemia

INTRODUCTION: Over the last decade, synthetic cannabinoids (SCB) have been marketed as a natural and safer version of marijuana, leading to an increase in its recreational use. We present a case of isolated hyperbilirubinemia caused by K2 and, to our knowledge, this is the first reported case of K2-induced indirect hyperbilirubinemia. CASE DESCRIPTION/METHODS: An 18-year-old male with no significant medical history presented with behavioral changes. He admitted to using K2 daily. His sibling and paternal uncle had Gilbert's syndrome. On physical exam he was withdrawn and agitated. He had Scleral icterus and jaundice. Slit Lamp exam was equivocal. On labs: Total Bilirubin 11.2 mg/dL, Indirect bilirubin 10.8 mg/dL, Urine toxicology positive for marijuana.Serum ceruloplasmin, serum copper, 24h urinary copper excretion, anti-mitochondrial Ab, anti-Nuclear Ab, anti-LKM, Soluble Liver antigen, ferritin, iron, TIBC, A1AT, A1AT phenotype, IgG, IgM, IgA, hepatitis A, B, C serologies, LDH, haptoglobin, uric acid, Coombs test, and G6PD levels were all within normal limits. His peripheral blood smear was normal. Imaging: MRI brain: unremarkable, Liver biopsy:normal hepatic architecture without severe pathological process (Figures 2a and 2b). He was treated with supportive care and indirect hyperbilirubinemia improved. DISCUSSION: • There is no current literature that correlates indirect hyperbilirubinemia and SCB use. In our otherwise healthy patient, this hyperbilirubinemia was likely a consequence of his K2 ingestion. We hypothesize that K2 may impair hepatic glucuronidation which is the process by which indirect bilirubin is converted to direct bilirubin. • During the time of exacerbation of Gilbert's disease, most often the indirect bilirubin levels remain < 5mg/dL. In the case of our patient, he presented with an indirect bilirubin level of 10.8 mg/dL. His work-up excluded other causes of indirect hyperbilirubinemia. • This leads us to hypothesize that K2 may induce significant isolated indirect hyperbilirubinemia in patients with a predisposition to impaired hepatic glucuronidation. • We believe that removal of the insulting agent is required for resolution of the hyperbilirubinemia. • With the use of SCB increasing recreationally, it is crucial we understand the effects these drugs can have. SCB do not appear on standard hospital drug screens. Therefore, a focused history and exam should be obtained from the patient. Our case serves to increase awareness of SCB use as a cause of indirect hyperbilirubinemia.Figure 1Figure (2a).: Liver biopsy stained with Hematoxylin & Eosin, showing normal hepatic architecture with no periductal or ductular inflammatory infiltration.Figure (2b).: Hepatic tissue stained with Periodid acid-Schiff Diastase and for copper; normal pathology & negative copper staining.

S3256 Hyperbilirubinemia in Chronis Hepatitis C Patients Treated With Protease Inhibitors

INTRODUCTION: Sofosbuvir/velpatasvir/voxilaprevir (SVV) and Glecaprevir/pibrentasvir (GP) are direct acting antiviral (DAA) agents used for chronic hepatitis C virus (HCV) infection. Both are pan-genotypic and used for treatment-experienced patients without cirrhosis or with compensated cirrhosis. Additionally, GP is approved in treatment-naïve patients. Hyperbilirubinemia has emerged as a potential adverse effect for these two medications due to significantly elevated NS3/4A protease inhibitor concentration. We aim to assess the incidence of hyperbilirubinemia in patients treated with these medications. METHODS: This is a retrospective study at a single tertiary care center. Patients who were treated with either SVV or GP between August 2017, and February 2020, were included. Patients who lost to follow-up were excluded. Laboratory exams were performed on a monthly basis. The population was analyzed based on treatment received: SVV +/- Ribavirin (RBV) and GP groups. Abnormal total bilirubin (Tbili) was defined as >1.2 mg/dL. Analyzed data included demographics, therapy history, achievement of sustained virologic response (SVR), hyperbilirubinemia incidence during the treatment period, timing and peak of T.bili, and all-cause mortality rate. RESULTS: Of the 229 charts reviewed, 196 met the inclusion criteria. Age ranged from 19 to 89 years old with a mean of 61, and 63% were males. 164 patients received GP, whereas 32 received SVV +/- RBV. Genotype 1 was the most prevalent. 25% of the population had compensated cirrhosis, and 4 patients underwent liver transplant. The incidence of hyperbilirubinemia was 12.8%, with a mean duration between therapy initiation and peak Tbili of 40 days. The highest Tbili measured was 6 mg/dL. 8.6% of patients had a peak Tbili >1.5 mg/dL, 3% had a peak Tbili >2 mg/dL, and only 1.5% had a peak Tbili >3 mg/dL. None of the patients had to stop therapy due to hyperbilirubinemia. The all-cause mortality rate was 2%, and causes were unrelated to hyperbilirubinemia or liver disease. There was no statistically significant difference in mean Tbili at treatment initiation or at peak between patients who received SVV +/- RBV and those who received GP, P = 0.227 and P = 0.129, respectively. CONCLUSION: Hyperbilirubinemia is a common side effect of DAAs containing NS3/4A protease inhibitors. Although it may not be clinically significant, clinicians should be mindful of potential hyperbilirubinemia and closely monitor chronic HCV patients treated with these agents with follow-up labs.

S1019 Indirect Bilirubin Predominates in Hyperbilirubinemia Due to Cirrhosis: Comparison With Alcoholic Hepatitis

INTRODUCTION: Research done in the 1950’s and 60’s described the occurrence of extravascular hemolysis in a subset of patients with alcoholic cirrhosis. Subsequent studies suggested that hemolysis in this setting is the result of acquired red blood cell abnormalities in the setting of hypersplenism. In the decades since, this phenomenon and its potential clinical significance have received little attention. The objective of this study was to examine levels of indirect hyperbilirubinemia in patients with different forms of advanced liver disease. METHODS: Clinical and laboratory data were compared among 3 groups of patients admitted to the University of Iowa Hospital between January 2010 and January 2018. Fifty subjects each with alcoholic hepatitis (AH), decompensated alcoholic cirrhosis (AC) and decompensated cirrhosis due to causes other than alcohol (N-AC) in whom fractionated bilirubin had been obtained at admission were selected for study. Statistical analysis was done using Excel. RESULTS: As would be expected, total bilirubin was significantly higher in AH versus AC and N-AC. Absolute levels of direct bilirubin were also highest in AH but the indirect bilirubin comprised only about a quarter of the total in this group. Conversely, the indirect bilirubin comprised nearly half of the total bilirubin in AC and about 60% in N-AC. Hemoglobin levels were similar among the groups, but RBC counts were slightly lower in AH versus N-AC. MCV, MCH, and MCHC were highest in AH, perhaps reflecting the effects of recent heavy alcohol ingestion. Spleen sizes were similar among the groups. CONCLUSION: Our data show that, in contrast to AH, hyperbilirubinemia in decompensated cirrhosis is characterized by a large indirect fraction. Indirect bilirubin in cirrhotic patients seems unlikely to be a direct consequence of the severity of the underlying liver disease, given that direct bilirubin predominates in severe AH, which indicates that the ability to conjugate bilirubin is preserved even in conditions of severe hepatocellular dysfunction. Extravascular hemolysis due to acquired red cell membrane abnormalities and/or hypersplenism may contribute to elevations in indirect bilirubin. Hemolysis markers (LDH, haptoglobin) were not routinely obtained in the patients in this study, limiting our ability to evaluate this possibility. Further study is needed to determine the cause and clinical significance of indirect hyperbilirubinemia in cirrhosis.Table 1.: Comparison of variables with features of advanced liver disease among three study groups; 1. alcoholic hepatitis (AH) 2. decompensated alcoholic cirrhosis (AC) and 3. decompensated non-alcoholic cirrhosis (N-AC)Table 2.: Comparison of clinical and laboratory data among the three study groups i.e. 1. alcoholic hepatitis (AH) 2. decompensated alcoholic cirrhosis (AC) and 3. decompensated non-alcoholic cirrhosis (N-AC)Figure 1.: Comparing the proportion of indirect bilirubin between three study groups.

Analysis of hyperbilirubinemia in patients with Kawasaki disease.

The present study attempted to analyze the clinical characteristics and pathogenesis of Kawasaki disease (KD) in children with hyperbilirubinemia.A total of 390 children with KD hospitalized in our hospital from September 2018 to July 2019 were selected and divided into control (270 cases) and hyperbilirubinemia (120 cases) groups based on the total, direct, and indirect bilirubin values after admission. Clinical data of the inflammatory index and fever process of the 2 groups were analyzed and compared.The difference in sex and age between the 2 groups was statistically nonsignificant (P > .05). In the hyperbilirubinemia group, the white blood cell count, C-reactive protein, hemoglobin, platelet count, erythrocyte sedimentation rate, alanine aminotransferase, aspartate aminotransferase, albumin, and routine urine leucocyte; and incidence of coronary artery expansion, heart injury, and unreactive gamma globulin treatment were higher than those in the control group and the differences were statistically significant (P < .05). In the hyperbilirubinemia group, the mean fever duration before admission was shorter than that in the control group, whereas the fever duration after gamma globulin treatment was longer than that in the control group; these differences were statistically significant (P < .05).Hyperbilirubinemia incidence in children with KD was approximately 30.77% (120 cases), of which increased direct bilirubin was observed in 70.83% (85 cases) and increased indirect bilirubin in 29.17% (35 cases). Children with KD combined with hyperbilirubinemia exhibited a strong inflammatory reaction, which may be due to liver damage or biliary block.

Evaluation of the safety and efficacy of glucocorticoid therapy for hyperbilirubinemia in patients with hepatocellular carcinoma who have undergone transcatheter arterial chemoembolization

Abstract Objective The aim of this study was to analyze the safety and efficacy of glucocorticoid treatment for hyperbilirubinemia in patients with hepatocellular carcinoma (HCC) who have undergone transcatheter arterial chemoembolization (TACE). Methods We conducted a retrospective analysis of the clinical data of 198 patients with HCC who were admitted to The Fifth Medical Center of PLA General Hospital from June 2014 to August 2019 and underwent TACE therapy. The patients were divided into glucocorticoid (GCC) treatment group and control group. Standard liver-protecting procedures were used in both groups. The treatment group also received intravenous injections of methylprednisolone sodium succinate for 3-5 days. Reduction in bilirubin concentration, mean duration of hospitalization, and complications were compared between the two groups to investigate the safety and efficacy of GCCs for treatment of hyperbilirubinemia after TACE treatment. Results Bilirubin concentrations were significantly lower in the treatment group than in control group on days 3 and 5 after GCC/conventional liver-protecting treatment (P &lt; 0.05). The treatment group had significantly shorter durations of total post-surgery hospitalization, and recovery time than the control group (14.5 ± 4.6 days vs. 17.5 ± 6.6 days, P &lt; 0.001; 9.2 ± 3.3 days vs. 11.8 ± 5.4 days, P = 0.001; 7.0 ± 3.3 days vs. 9.3 ± 4.6 days, P &lt; 0.001). No GCC-associated complications were detected in the treatment group. Conclusion Short-term use of GCCs to treat hyperbilirubinemia in patients with HCC who have undergone TACE is safe and associated with rapid decline in bilirubin concentration and shorter hospital stay compared with patients who did not receive GCCs.

The prevalence and prognostic implications of pre-procedural hyperbilirubinemia in patients undergoing transcatheter aortic valve replacement.

Preoperative hyperbilirubinemia is associated with increased mortality and morbidity after cardiac surgery. However, this clinical significance is unclear with transcatheter aortic valve replacement (TAVR) procedures. The aims of this study were to determine the prevalence and prognostic implications of preoperative elevations of serum total bilirubin on TAVR outcomes. In 611 consecutive patients who underwent an elective TAVR procedure, 576 patients had recorded serum total bilirubin levels. Hyperbilirubinemia was defined as any value of serum total bilirubin ≥ 1.2mg/dL obtained within 30-days prior to the TAVR procedure. The primary composite endpoint was post-TAVR all-cause in-hospital mortality or stroke. The overall prevalence of hyperbilirubinemia was 10% (n = 58). There were no patients with a prespecified diagnosis of liver cirrhosis. Pre-TAVR hyperbilirubinemia compared to normal bilirubin level was more common in younger (78 ± 10 vs. 82 ± 8years old, p < 0.001) males (15 vs. 6%, p < 0.001), with history of pacemaker or ICD (33 vs. 18%, p = 0.005), congestive heart failure New York Heart Association class IV within 2weeks from TAVR (35 vs. 14%, p < 0.001), severe tricuspid regurgitation (14 vs. 4%, p < 0.001), and atrial fibrillation or flutter (60 vs. 40%, p = 0.004, respectively). Pre-TAVR hyperbilirubinemia was independently associated with an increased post-TAVR in-hospital mortality (7 vs. 2% in normal bilirubin, p = 0.03), stroke (5 vs. 1%, p = 0.019, respectively), and a composite endpoint of death or stroke (12 vs. 3%, p < 0.001). Preoperative hyperbilirubinemia in patients undergoing TAVR is more prevalent than previously considered with multifactorial causes. Hyperbilirubinemia is independently associated with an increased post-TAVR in-hospital mortality and stroke.

Resolution of grossly discrepant inter-analyser bilirubin results in patients on eltrombopag therapy: A hepatotoxic drug that affects bilirubin measurement

Background: Eltrombopag is a thrombopoietin receptor agonist that is increasingly being prescribed for the treatment of chronic thrombocytopenic conditions. Hepatotoxicity occurring in ∼15% of patients necessitates regular monitoring of liver function. Depending in which hospital a patient is followed-up, serum bilirubin concentration for a single sample can vary by more than 8-fold, or 64 μmol/L, with the true concentration unknown. Methods: Bilirubin was measured using up to nine assays including the Doumas Reference method and HPLC, for 66 samples from patients on 25–150 mg daily. Plasma/serum eltrombopag concentrations were determined using LC-MS/MS. Results: There was a positive correlation between inter-analyser total bilirubin difference and plasma eltrombopag concentration (r=0.679). Spike-in experiments demonstrated that methods including the Doumas reference method were susceptible to positive interference. HPLC quantified bilirubin after separating eltrombopag, and results show that different analysers are affected to varying degrees by eltrombopag and its metabolites. Conclusions: We are the first to demonstrate which bilirubin assays can accurately quantitate bilirubin concentration in patients on eltrombopag therapy. We are also the first to provide evidence that metabolites likely contribute to the interference. Resolution of inter-analyser discrepancies may prevent misdiagnosis of hepatotoxicity and improve our understanding of the prevalence of hyperbilirubinaemia in patients on eltrombopag therapy.

Relationship between elevated bilirubin level and subclinical atherosclerosis as well as oxidative stress in Gilbert syndrome.

This study aimed to determine oxidant status and left ventricular mass index (LVMI) and their relationship with mild hyperbilirubinemia in patients with Gilbert syndrome (GS). Gilbert syndrome (GS) presents with mild indirect hyperbilirubinemia, normal liver function tests, and normal hepatic histology. A total of 84 patients, including 41 (48.8%) patients with GS and 43 (51.2%) patients without GS, were included in the study. Total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were examined for oxidant status. TAS was found to be higher in the GS patients compared to the non-GS patients (1.7±0.1 vs. 1.5±0.2; p=0.002); there was no significant difference between the groups in terms of mean TOS and mean OSI (p>0.05). No significant difference was observed either between the GS and non-GS patients in terms of mean left ventricular volume and mean LVMI (p>0.05). However, subgroup analysis based on sex revealed that GS patients had a lower LVMI for both sexes. In GS patients, TAS level had a positive correlation with albumin (r=0.319; p=0.042), triglyceride (r=0.392; p=0.011), total bilirubin (r=0.420; p=0.006), direct bilirubin (r=0.361; p=0.020), and indirect bilirubin (r=0.338; p=0.0311) levels; no correlation was found between TAS level and other laboratory findings (p>0.05). The regression model indicated that risk factors of direct bilirubin (β±SE=0.13±0.03; p<0.001), uric acid (β±SE=0.04±0.01; p=0.001), and albumin (β±SE=0.17±0.04; p<0.001) were independent predictors of TAS level. This study revealed a relationship between mild hyperbilirubinemia and antioxidant balance in GS. Although statistical significance was not reached, LVMI was found to be lower in the GS group compared to the non-GS group for both sexes.

Comprehensive characterization and resolution of discrepant spectrophotometric bilirubin results in patients on eltrombopag therapy.

Background Eltrombopag is a thrombopoietin receptor agonist used for the treatment of thrombocytopenic conditions. It can cause pH-dependent discoloration of plasma/serum. Eltrombopag is potentially hepatotoxic. It can affect the assessment of hyperbilirubinemia because of its (i) absorbance at ~450 nm (bilirubin), (ii) absorbance at ~550 nm (diazo-bilirubin) and (iii) it can cause yellowish discoloration of the eyes at normal circulating bilirubin levels. Methods We collected 66 samples from patients on a range of eltrombopag dosages up to 150 mg daily. Bilirubin was measured using multiple routine spectrophotometric analyzers, the Doumas reference method and high-performance liquid chromatography (HPLC). Plasma/serum eltrombopag concentrations were determined using liquid chromatography tandem mass spectrometry (LC-MS/MS). Spike-in and admixture experiments delineated the effects of eltrombopag and its metabolites. Results Forty-nine of 52 samples from patients on ≥50 mg daily eltrombopag therapy showed significantly discrepant inter-analyzer total bilirubin results, a difference up to 64 μmol/L (3.7 mg/dL). In one sample, total bilirubin varied from 8 to 65 μmol/L (0.4-3.8 mg/dL) by different routine analyzers, with direct bilirubin ≤4 μmol/L (0.2 mg/dL). There was a positive correlation between total bilirubin difference and plasma eltrombopag concentration (r = 0.679), and spike-in experiments demonstrated that Beckman AU and Doumas reference methods were susceptible to positive interference. HPLC can quantify bilirubin after separating eltrombopag, and results suggest different analyzers are affected to varying degrees by eltrombopag and its metabolites. Conclusions Eltrombopag and its metabolites can cause positive interference to the spectrophotometric measurements of total bilirubin. Accurate measurements of total bilirubin may improve our understanding of the prevalence of hyperbilirubinemia in patients on eltrombopag therapy.

Sa1544 – Evaluation of Hyperbilirubinemia in Patients Who Present with Acute Cholecystitis

Sa1544 – Evaluation of Hyperbilirubinemia in Patients Who Present with Acute Cholecystitis

Relevance of Preoperative Hyperbilirubinemia in Patients Undergoing Hepatobiliary Resection for Hilar Cholangiocarcinoma.

Preoperative hyperbilirubinemia is known to increase the risk of mortality and morbidity in patients undergoing resection for hilar cholangiocarcinoma. The aim of this study was to characterize the associations between the preoperative bilirubin concentration and the risk of postoperative mortality and severe complications to guide decision-making regarding preoperative biliary drainage. Eighty-one patients undergoing liver and bile duct resection for hilar cholangiocarcinoma between 2005 and 2015 were analyzed retrospectively. Postoperative mortality and severe complications, defined as a Clavien–Dindo grade of ≥III, were the primary and secondary outcome measures, respectively. The severe postoperative complications and mortality rates were 28.4% (23/81) and 11.1% (9/81), respectively. Patients with preoperative biliary drainage had significantly lower bilirubin concentrations (p = 0.028) than did those without. The preoperative bilirubin concentration was a risk factor of postoperative mortality (p = 0.003), with an optimal cut-off of 6.20 mg/dL (c-statistic = 0.829). The preoperative bilirubin concentration was a risk factor of severe morbidity (p = 0.018), with an optimal cut-off of 2.48 mg/dL (c-statistic = 0.662). These results indicate that preoperative hyperbilirubinemia is a major risk factor of negative early postoperative outcomes of patients who undergo surgical treatment for hilar cholangiocarcinoma and may aid in decision-making with respect to preoperative biliary drainage.