Elevated Serum Total Bilirubin Levels Research Articles

Recovery from antibody-mediated biliary ductopenia and multiorgan inflammation after COVID-19 vaccination

The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of a previously healthy 47-year-old man, who developed progressive jaundice 2 weeks after receiving his 3rd COVID-19 vaccination (1st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at >70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108.5 mg/dL; creatinine: peak, 6 mg/dL) and exocrine pancreas (amylase: peak, 1717 U/L; lipase: peak, 5784 U/L) profiles were also seen. Vanishing bile duct syndrome characterized by ductopenia and cholangiocyte vacuolation, positive C4d deposition, and high titer of anti-angiotensin II type 1 receptor antibody consistently explain the overall antibody-mediated pathogenesis resembling antibody-mediated “rejection” in the solid organ transplant setting. Corticosteroids and plasmapheresis were administered, leading to gradual resolution of the symptoms, and the jaundice completely resolved 2 months later. In conclusion, we reported a case of antibody-mediated multiorgan injury after an mRNA COVID-19 vaccine, characterized by severe cholangiopathy. The patient recovered with corticosteroids and plasmapheresis, and long-term follow-up is necessary.

Risk Factors for Prognosis after the Maze IV Procedure in Patients with Atrial Fibrillation Undergoing Valve Surgery

The present study evaluated risk factors related to persistent atrial fibrillation (AF) at discharge (AF-d) and recurrent atrial fibrillation (rAF) and all-cause death after the maze IV procedure. Two hundred nineteen patients (63 female, aged 52.5±8.8 years) with valve disease and persistent AF undergoing valve surgery and the maze IV procedure in our center between 2015 and 2016 were included. Baseline demographic and clinical data were obtained by review of medical records. The median follow-up period was 27 months (interquartile range 21–34 months) in our patient cohort. The primary end point was all-cause death. The secondary end point was AF-d or rAF. rAF is defined as AF recurrence at 3 months or later after the procedure. Twenty-eight patients (12.8%) died during follow-up. Multiple logistic regression analysis showed that thrombocytopenia, elevated serum total bilirubin level, a larger right atrium, AF-d, and rAF were independent determinants for all-cause death after the maze IV procedure after adjustment for age, sex, and clinical covariates, including New York Heart Association class III/IV disease, hypertension, and aortic regurgitation, while valvular disease duration and left atrial diameter greater than 80.5 mm were independent determinants for AF-d, and thrombocytopenia, elevated serum total bilirubin level, higher mean pulmonary artery pressure, and AF-d were independent predictors for rAF. In conclusion, thrombocytopenia, elevated serum total bilirubin level, an enlarged right atrium, AF-d, and rAF are independent predictors of all-cause death in patients undergoing the maze IV procedure.

Rapid Improvement in Jaundice Using Transdermal Isosorbide Tape as a Nitric Oxide Donor in Two Adult Patients with Transplantation-associated Microangiopathy Related to Graft-versus-host Disease.

Two adult patients with acute leukemia developed transplantation-associated microangiopathy (TAM) related to graft-versus-host disease (GVHD). Both patients were resistant to standard therapy for TAM and GVHD, which led to markedly elevated serum total bilirubin levels of 47.5 and 10.6 mg/dL, respectively. Transdermal isosorbide tape as a nitric oxide donor was applied to Patients 1 and 2 on post-transplantation days 60 and 66, respectively, which rapidly improved their jaundice after 1 day. This is the first report to describe the efficacy of transdermal isosorbide tape for adult patients with jaundice associated with TAM related to GVHD.

Lipid-Free PN is Associated with an Increased Risk of Hyperbilirubinemia in Surgical Critically Ill Patients with Admission Hepatic Disorder: A Retrospective Observational Study.

BackgroundTo evaluate the effect of different PN types on surgical critically ill trauma/acute care surgery patients with hepatic disorders at admission.MethodsThis is a retrospective study. The PN types included lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish oil-containing PNs. Patients admitted with liver injury or liver surgery, elevated serum AST/ALT level, and elevated serum total bilirubin level were included. The exclusion criteria are as follows: 1) age <18 years, 2) severe liver disease/cirrhosis, 3) received more than one type of PN and 4) serum total bilirubin >4.9 mg/dl at admission. Demographics, severity, comorbidities, blood stream infection, hyperbilirubinemia (total bilirubin > 6.0 mg/dl), and mortality were collected for analysis. We also performed analysis stratified by separated lipid doses (g/kg/day).ResultsA total of 156 patients were enrolled. There were no demographic differences among groups. The lipid-free group was associated with the highest mortality rate and incidence of hyperbilirubinemia. Compared to the lipid-free group, the olive oil-based group had the lowest risk of hyperbilirubinemia. After being stratified by separated lipid doses, the incidence of hyperbilirubinemia decreased when the lipid dosage increased. Regarding different types of lipids, patients who received more than the median dosage of lipids showed a significantly lower risk of hyperbilirubinemia, except in the fish oil-containing group.ConclusionOur result suggested that lipid-free PN is associated with an increased risk of hyperbilirubinemia in surgical critically ill patients with admission hepatic disorder. Further studies are warranted.

Serum Bilirubin level and its correlation with white blood cells as risk factor for cardiovascular disease in adult healthy population.

Objectives: Evaluate serum bilirubin in adult healthy subjects and its correlation with white blood cells as risk factor for cardiovascular disease. Study Design: Cross- sectional study. Setting: Department of Pharmacology and Medicine, Suleman Roshan Medical College. Period: January - December 2017. Material &amp; Methods: A sample of 100 male and 100 female adult healthy subjects were recruited for study protocol. Blood glucose, Serum creatinine, Blood lipids, liver enzyme levels, White blood cell counts and Serum bilirubin levels were analyzed. Pearson`s correlation was used for the correlation coefficient and its statistical significance for the association of serum bilirubin and white blood cells. Data variables were analyzed by statistical software SPSS (ver 21.0) at 95% CI (P ≤ 0.05). Results: Mean± SD age of male and female was found 47.02±8.42 and 48.59±7.80 years respectively (P=0.071). Serum bilirubin shows statistically significant negative correlation with blood glucose (r= - 0.257, P=0.0001) and LDLc (r= - 0.155, P=0.027) and WBC (r= - 0.871, P=0.0001). Conclusion: The present study shows the elevated serum total bilirubin levels within reference range correlated negatively with total white blood cells in adult healthy population.

Role of Hyperbilirubinemia as a Diagnostic Tool to Predict Gangrenous/Perforated Appendicitis: An Observational Study

Background: Elevation in serum bilirubin was reported recently, but the importance of the raised total bilirubin has not been stressed in acute appendicitis and appendicular perforation. The aim of the study was to establish the role of hyperbilirubinemia as a new diagnostic tool to predict gangrenous/perforated appendicitis. Subjects and Methods: This was a prospective observational study, which was conducted at the Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. A total of 100 patients clinically diagnosed as appendicitis from August 2018 to August 2019 at Gujarat Adani Institute of Medical Science, Bhuj, Kutch, Gujarat, India. Patients were clinically evaluated by detailed history, routine examination on initial contact with patients and the routine investigations as per surgery and anesthesia requirements with inclusion of serum total bilirubin. Based on histopathological examination patients will be categorized as positive (acute appendicitis with perforation and/or gangrene) and negative (acute appendicitis without perforation or gangrene). Results: Out of 100 patients, 20 were managed conservatively (mass formation) and was called for interval appendectomy after 6 weeks. In acute catarrhal appendicitis group 47 patients showed normal total bilirubin levels, whereas 8 patients showed increase in levels of total bilirubin. In gangrenous appendicitis group all 10 patients showed elevated serum total bilirubin levels In perforated appendicitis group consisted of 15, 11 patients showed elevated serum bilirubin levels and 4 patients showed normal total bilirubin levels. Conclusion: Serum bilirubin is easily available test and cheap and can be estimated from the sample of blood drawn for routine blood investigations.

Elevated Serum Total Bilirubin Level Is Associated with Poor Outcomes in Pediatric Patients with Sepsis-Associated Liver Injury.

Aims The aim of this study was to assess the prognostic value of the serum total bilirubin (TBIL) level in pediatric patients with sepsis-associated liver injury (SALI). Methods We performed a retrospective study of patients with SALI admitted to the pediatric intensive care unit (PICU) in Shanghai Children's Hospital between December 2012 and December 2015. Serum TBIL concentration was determined within 72 h after PICU admission. Results Seventy-two patients with SALI were included in this study. The overall mortality rate was 36.1% (26/72). The serum levels of TBIL of patients were significantly higher in the nonsurvivor group than the survivor group. Cox regression analysis indicated that the elevated serum TBIL level within 72 hours after admission was an independent risk factor of mortality in patients with SALI. Furthermore, the area under the receiver-operating characteristic (ROC) curve (AUC) for TBIL was 0.736 (95% confidence interval (CI): 0.614–0.858, P=0.001), in which the optimal cut-off value was 64.5 μmol/L. The combined index named “TBIL” and “TBA” showed an AUC of 0.745 (0.626–0.865) for predicting the prognosis in patients with SALI. In addition, the Kaplan–Meier curve indicated that the 28-day survival rate was significantly lower in patients with higher serum TBIL levels (≥64.5 μmol/L) or higher value of TBIL and TBA (≥−0.8902). Conclusions Elevated serum TBIL level is associated with poor outcomes in pediatric SALI.

Serum bilirubin level and its impact on the progression of chronic kidney disease.

To examine whether an elevated serum total bilirubin level affects the decline in renal function or new-onset chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (DM2). This was a longitudinal observational study in patients who presented at the University of Health Sciences Hospital in Kayseri. Five hundred twenty-nine patients with DM2 who had conserved renal function were enrolled (estimated glomerular filtration rate > 60ml/min/1.73m2). Arising CKD stage 3 was the outcome measure. The patients were separated into three groups based on the total serum bilirubin levels. The first group (G1) ranged from 0.1 to 0.3, the second (G2) 0.4-0.5, and the third (G3) 0.6-0.9mg/dl. The effect of total serum bilirubin levels on CKD 3 development was assessed using Cox proportional hazards regression. The risk of the CKD stage 3 development was highest in G1 who has the lowest serum total bilirubin levels (G1 vs. G3; hazard ratio [HR], 2.02; 95% confidence interval [CI] 1.21-3.36; p = 0.007). In addition, G2 had a significant risk of CKD stage 3 development (G2 vs. G3; hazard ratio [HR], 1.58; 95% confidence interval [CI] 1.08-2.32; p = 0.018). In the adjusted analysis, compared to G2 and G3, G1 had the highest risk (G1 vs. G3; hazard ratio [HR], 2.20; 95% confidence interval [CI] 1.29-3.77; p = 0.004). Similarly, G2 had a higher risk compared to G3 (hazard ratio [HR], 1.57; 95% confidence interval [CI] 1.05-2.34; p = 0.028). Serum bilirubin may predict the progression of CKD in patients with type 2 diabetes and preserved kidney function.

Validity of Serum Total Bilirubin as a Diagnostic Tool for Acute Appendicitis

Objective: To study the relationship between hyperbilirubinemia and acute appendicitis and to evaluate its credibility as a diagnostic marker for acute appendicitis and to evaluate whether elevated serum total bilirubin levels have a predictive potential for the diagnosis of complicated appendicitis Background: In acute appendicitis occurs through bacterial invasion in appendix leads to transmigration of bacteria and release of TNF-alpha, IL6 and cytokines. These reach the liver through superior mesenteric vein and may produce inflammation or dysfunction of liver either directly or indirectly by altering hepatic blood flow with rising of total serum bilirubin. Methods: This is a prospective cohort study including Ninety four (94) of adult patients have right iliac fossa pain attending to the Emergency Department (ED) at Suez Canal university Hospital. All 94 patients undergo total serum bilirubin measuring and post-operative histopathological examination of removed appendix. Results: In this study population of 94 patients and found that thirty-six male patient (38 %) and fifty-eight female patient (62 %), 81 patients (86.2%) were diagnosed as acute appendicitis while 13 patients (13.8%) were normal post-operatively by histopathological reports. Amongst the patients diagnosed with Acute appendicitis post-operatively, 57 patients (70.4%) were found to have elevated serum total bilirubin (>1.2mg/dL) while 24 patients (29.6%) had normal serum total bilirubin levels (≤1.2 mg/dL). Conclusion: Serum total bilirubin level appears to be a promising new laboratory marker for diagnosing acute appendicitis and have a predictive potential for the diagnosis of complicated appendicitis.

Hyperbilirubinemia as a Significant Indicator in Diagnosis of Complicated Acute Appendicitis: A Prospective Study

Background: Acute appendicitis is the most common cause of acute abdomen in young adults. In recent years, studies emerged showing that elevated serum total bilirubin levels could indicate a complicated case of acute appendicitis. An elevated serum total bilirubin that is not explained by liver disease or biliary obstruction can be present in many patients of acute appendicitis. Patients and methods: This is a prospective interventional non-randomized non-controlled study conducted on 175 consecutive cases of acute appendicitis admitted to the emergency unit in the Department of General Surgery at Ain Shams University hospitals, Cairo, Egypt in the period from July 2014 to August 2016. Liver function tests were done as a part of the preoperative investigations. Clinical diagnosis was confirmed postoperatively by histopathological examination. Their clinical and investigative data were analyzed, The level of significance was set at P< 0.05. Results: Serum total bilirubin was found to be significantly elevated in cases of complicated acute appendicitis. Conclusion: Serum total bilirubin is a new important adjunct in the diagnosis of complicated acute appendicitis.

Elevated serum total bilirubin levels are negatively associated with major diabetic complications among Chinese senile diabetic patients

AimsThis study aimed to evaluate the association between total bilirubin (TBiL) and major diabetic complications among Chinese senile diabetic patients. MethodsA cross-sectional study was conducted in all the cadre sanitariums in Beijing, between May 2012 and December 2014. All the diagnoses of diabetic complications were extracted from the medical records including chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease, and ischemic stroke. ResultsThe mean age of the 1839 senile diabetic patients were 87.4±4.0 (80–102years) and mean TBiL level was 13.2±6.0μmol/L. The prevalence of chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke was 13.8%, 17.8%, 5.8%, 62.5%, and 44.5%, respectively. TBiL level was negatively correlated with age, weight, SBP, TC, FBG, 2hPG, diabetic duration and positively correlated with HDL-C. Prevalence of all five diseases gradually decreased with the increase of TBiL level (p<0.05). Also, number of diabetic complications showed a decreasing trend along with TBiL tertiaries. After adjusted age, education, marital status, current smoking, current drinking, physical activity ≥0.5h/day, BMI, hypertension, dyslipidemia, treatment and control status of diabetes, patients with higher TBiL level were at significantly decreased ORs for prevalence of major diabetic complications. The ORs were 0.97 (95%CI: 0.96–0.99), 0.90 (95%CI: 0.87–0.93), 0.98 (95%CI: 0.97–0.99), 0.97 (95%CI: 0.95–.99) and 0.98 (95%CI: 0.97–0.99) for chronic kidney disease, retinopathy, peripheral vascular disease, coronary heart disease and ischemic stroke (p<0.005). Similar results were obtained when TBiL was used as tertiary variable. ConclusionHigher TBiL was significantly associated with lower prevalence of major diabetic complication among senile diabetic patients, and this association was graded with TBiL level and independent of age and control status of diabetes.

Variable Use of Model for End-Stage Liver Disease Exception Points in Patients With Neuroendocrine Tumors Metastatic to the Liver and Its Impact on Patient Outcomes.

The role of liver transplantation in management of patients with metastatic neuroendocrine tumors (NETs) is controversial. Because many such patients have low waitlist priority, centers may apply for model for end-stage liver disease (MELD) exception points to increase likelihood of receiving a liver transplant. No formal criteria exist for application or receipt of exception points for this indication. Few studies have assessed waitlist and posttransplantation outcomes in patients with metastatic NETs, and none examined the impact of exception points. We analyzed all adult patients waitlisted for liver transplantation for metastatic NETs between February 27, 2002, and June 4, 2014, and fit a multivariable model to evaluate the association between exception point status and posttransplantation outcomes. There was variable use of MELD exception points across the United Network for Organ Sharing regions. Patients with an approved MELD exception were nearly twice as likely to be transplanted as those without exceptions (70.8% vs 39.1%, P < 0.001), and half as likely to be removed for death or clinical deterioration (9.2% vs 18.2%, P = 0.046). In multivariable models, posttransplantation survival was not associated with receipt of exception points, whereas risk of posttransplant mortality increased significantly with elevated serum total bilirubin level at transplantation. The 3-year posttransplant patient survival was 78% in transplant recipients with metastatic NETs whose total bilirubin level at transplantation was 1.3 mg/dL or less, compared to 36% in those with total bilirubin greater than 1.3 mg/dL. Serum total bilirubin may serve as a predictor of poor posttransplant survival in patients with metastatic NETs and could help risk-stratify patients applying for MELD exception points.

Serum total bilirubin levels and coronary heart disease — Causal association or epiphenomenon?

Observational epidemiological evidence supports a linear inverse and independent association between serum total bilirubin levels and coronary heart disease (CHD) risk, but whether this association is causal remains to be ascertained. A Mendelian randomization approach was employed to test whether serum total bilirubin is causally linked to CHD. The genetic variant rs6742078 – well known to specifically modify levels of serum total bilirubin and accounting for up to 20% of the variance in circulating serum total bilirubin levels – was used as an instrumental variable. In pooled analysis of estimates reported from published genome-wide association studies, every copy of the T allele of rs6742078 was associated with 0.42 standard deviation (SD) higher levels of serum total bilirubin (95% confidence interval, 0.40 to 0.43). Based on combined data from the Coronary Artery Disease Genome wide Replication and Meta-analyses and the Coronary Artery Disease (C4D) Genetics Consortium involving a total of 36,763 CHD cases and 76,997 controls, the odds ratio for CHD per copy of the T allele was 1.01 (95% confidence interval, 0.99 to 1.04). The odds ratio of CHD for a 1 SD genetically elevated serum total bilirubin level was 1.03 (95% confidence interval, 0.98 to 1.09). The current findings casts doubt on a strong causal association of serum total bilirubin levels with CHD. The inverse associations demonstrated in observational studies may be driven by biases such as unmeasured confounding and/or reverse causation. However, further research in large-scale consortia is needed.

Mildly elevated serum total bilirubin levels are negatively associated with carotid atherosclerosis among elderly persons with type 2 diabetes

Diabetes is strongly associated with several mechanisms of tissue damage such as oxidative stress. Serum bilirubin may have a beneficial role in preventing oxidative changes in cardiovascular disease (CVD). Limited information is available on whether serum bilirubin is an independent confounding factor for carotid atherosclerosis among elderly persons with type 2 diabetes. The study subjects were 169 men aged 79 ± 8 (mean ± SD) years and 205 women aged 81 ± 8 years that were enrolled consecutively from patients in the medical department. Carotid intima-media thickness (IMT) and plaque were derived via B-mode ultrasonography. Multiple linear regression analysis showed that serum total bilirubin (β = −0.160) was significantly associated with carotid IMT. Compared to subjects with a serum total bilirubin of tertile-1 (0.13–0.58 mg/dL), the multivariate-adjusted odds ratio (95% confidence interval) of carotid IMT ≥1.0 mm including plaque and carotid plaque was 0.46 (0.23–0.93) and 0.32 (0.17–0.60) in the Tertile-3 group (0.87–1.93 mg/dL), respectively. Next, data were further stratified by gender, age, smoking status, medication and prevalence of CVD. There were no significant differences in serum total bilirubin levels between selected subgroups. Our data demonstrated a negative association between serum total bilirubin and carotid atherosclerosis among elderly persons with type 2 diabetes.

Prognostic Factors in Patients with Hepatocellular Carcinoma Refractory or Intolerant to Sorafenib

Objective: The aim of this study was to identify the prognostic factors in patients with advanced hepatocellular carcinoma (HCC) who are refractory or intolerant to sorafenib and to exclude unsuitable candidates from subsequent therapy. Methods: The study cohort consisted of 111 patients who had discontinued sorafenib therapy. Uni- and multivariate analyses were conducted to identify the prognostic factors for survival after discontinuation of sorafenib therapy. Results: The median age of the patients was 70 years, and 96 of them (86%) were male. The Eastern Cooperative Oncology Group performance status was 0-1 in 94 patients (85%). Forty patients (36%) were classified as Child-Pugh class A and 57 (51%) as Child-Pugh class B. The median survival time after discontinuation of sorafenib therapy was 146 days. Hepatitis C viral antibody negativity, presence of ascites, absence of a history of previous treatment excluding sorafenib, elevated serum total bilirubin level, and elevated serum α-fetoprotein level were identified as the independent unfavorable prognostic factors by multivariate analysis. The median survival time of the patients with 4 or 5 unfavorable prognostic factors was 59 days. Conclusions: We should judge the indication of any subsequent therapy carefully in patients with 4 or 5 of the aforementioned factors. © 2014 S. Karger AG, Basel

Pharmacokinetic, tolerability, and bioequivalence comparison of three different intravenous formulations of recombinant human erythropoietin in healthy Korean adult male volunteers: An open-label, randomized-sequence, three-treatment, three-way crossover study

Background: Existing formulations of recombinant human erythropoietin (rhEPO) in Korea contain human serum albumin. To avoid the potential risk of infection by human serum albumin, a new albumin-free rhEPO has been developed. Objective: This study was conducted to characterize and compare the pharmacokinetic and safety profiles and the bioequivalence of a newly developed albumin-free rhEPO (Aropotin® [TS Corporation, Seoul, South Korea]) with 2 existing rhEPO formulations (Espogen® [LG Life Sciences, Seoul, South Korea]; Recormon® [Roche, Basel, Switzerland]) with albumin in healthy Korean subjects. Methods: This was an open-label, randomized-sequence, 3-treatment, 3-way crossover study in which healthy, nonobese (±20% of ideal weight), male volunteers between the ages of 19 and 50 years were assigned to 1 of 2 dose levels (50 IU/kg or 100 IU/kg) of 3 formulations. Blood was collected over 32 hours and plasma rhEPO concentrations were determined using a validated enzyme immunoassay. There was a 14-day washout between periods. The pharmacoki-netic parameters of the 3 formulations were compared using the bioequivalence criteria of the US Food and Drug Administration, which requires that the 90% CIs of the geometric mean ratios for AUC 0−t, AUC 0−∞, and C max fall within 0.80 to 1.25. Tolerability was evaluated by physical examination with measurements of vital signs, clinical laboratory tests, and electrocardiogram. Subjects were followed up for 2 weeks after the last administration of study drug. Results: Twelve Korean male volunteers were enrolled and completed the study. Six subjects (mean [SD] age, 22.0 [1.7] years; weight, 63.3 [6.2] kg; height, 172.3 [3.5] cm) received a single 50 IU/kg IV bolus dose of study drug and the remaining 6 subjects (mean [SD] age, 23.7 [1.5] years; weight, 66.3 [4.8] kg; height, 174 [4.7] cm) received 100 IU/kg. After a single 50 IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/Espogen was 1.04 (0.91–1.19) IU/L/h for AUC 0−t and 1.02 (0.89–1.17) IU/L for C max. The geometric mean ratio (90% CI) for Aropotin/Recormon was 1.01 (0.88−1.15) IU/L/h for AUC 0−t and 1.01 (0.89–1.16) IU/L for C max. After a single 100-IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/ Espogen was 0.98 (0.86–1.13) IU/L/h for AUC 0−t and 0.99 (0.87–1.13) IU/L for C max. The geometric mean ratio (90% CI) for Aropotin/Recormon was 0.99 (0.861.14) IU/L/h for AUC 0−t and 0.96 (0.84–1.10) IU/L for C max. The most frequent adverse events (AEs) were 3 occurrences of elevated serum creatine phosphokinase and serum lactate dehydrogenase levels in the Recormon 100-IU/kg group (n = 3), 3 events of elevated serum lactate dehydrogenase levels in the Espogen 100-IU/kg group (n = 3), and 4 events of elevated serum total bilirubin levels in the Aropotin 100-IU/kg group (n = 3). All formulations were well tolerated with no serious AEs. Conclusion: The new formulation of rhEPO met the regulatory criteria for bioequivalence in these healthy Korean adult male volunteers. All formulations were generally well tolerated.

False Positive Acetaminophen Levels Associated with Hyperbilirubinemia

Serum acetaminophen determination is frequently necessary in patients with hepatic failure. We observed two patients (#1, #2) with elevated serum total bilirubin levels (26.5 mg/dL and 40.1 mg/dL) who had multiple false positive acetaminophen levels using the kinetic method of the GDS Diagnostics enzymatic acetaminophen assay (GDS Diagnostics, Elkhart, IN). We investigated the magnitude, threshold, and linearity of this effect using the GDS Diagnostics assay and an EMIT acetaminophen assay on two other hyperbilirubinemic patients (#3, #4) and a commercial solubilized bilirubin standard. Samples were diluted using fresh frozen plasma, and acetaminophen levels were analyzed twice using the kinetic method of the GDS Diagnostic acetaminophen assay and twice with the EMIT assay. The absence of acetaminophen in all samples was verified by gas chromatography/mass spectroscopy (GC/MS). The kinetic GDS assay resulted in a positive acetaminophen assay (cutoff for a positive result = 10 mg/L) with patient #3, patient #4, and in the bilirubin standard when the total bilirubin levels were 28.2 mg/dL, 22.5 mg/dL, and 18.3 mg/dL, respectively. One sample was interpolated to give a positive acetaminophen reading when diluted to a total bilirubin concentration of 15 mg/L. None of the samples tested with GC/MS or the EMIT assay resulted in any detectable acetaminophen. In conclusion, caution must be taken utilizing the GDS Diagnostic assay for the quantification of acetaminophen with concomitant hyperbilirubinemia. Alternatives such as EMIT or GC/MS should be employed to assess acetaminophen levels in such patients.