The U-shaped association between serum direct bilirubin and incident mild cognitive impairment in hemodialysis patients: a multicenter study.

BACKGROUND: Previous studies have suggested an association between low serum bilirubin concentrations and increased risk of cognitive impairment. This study aimed to explore the association and dose-response relationship between serum direct bilirubin (DBIL) concentrations and mild cognitive impairment (MCI) among hemodialysis patients. METHODS: This is a multicenter cross-sectional study with patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China. The outcome was mild cognitive impairment (MCI), measured with a Mini-Mental State Examination. The association and dose-response relationship between serum DBIL and MCI incidence were examined using multivariate logistic regression analysis, restricted cubic spline, and subgroup analysis to explore the association of serum DBIL concentrations with MCI. RESULTS: Of the 4223 enrolled patients (mean age 55.2 ± 15.3 years, 60.4% males), 1187 (28.1%) had MCI. Serum DBIL of 0.10-1.67umol/L [multivariable-adjusted odds ratios (OR) 1.32, 95% confidence interval (CI): 1.08-1.60, P = 0.005], 2.31-3.20umol/L (OR = 1.22, 95%CI: 1.00-1.49, P = 0.047), and > 3.21umol/L (OR = 1.32, 95%CI: 1.08-1.61, P = 0.006) had increased risk of MCI compared with 1.68-2.30umol/L. The dose-response analysis between serum DBIL and MCI showed a U-shaped relationship (P for non-linearity = 0.009), and the serum DBIL concentrations with the lowest risk of MCI was 2.01umol/L. As the serum DBIL concentrations were lower than the reference, the risk of MCI decreased by 49% per standard deviation (SD) increase in serum DBIL (OR = 0.51, 95%CI: 0.29-0.89, P < 0.001); when the concentration exceeds 2.01umol/L, a rise per SD increased the risk of MCI by 9% (OR = 1.09, 95%CI:1.01-1.17, P < 0.001). CONCLUSION: Our findings suggest a U-shaped association between serum DBIL and MCI among hemodialysis patients.

Recovery from parenteral nutrition-associated cholestasis takes approximately two months in very low birth weight infants.

AIM: To investigate the clinical characteristics and course of parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants. METHODS: The charts of VLBW infants were retrospectively reviewed. The clinical characteristics of infants with and without PNAC were compared, trends in liver enzymes were investigated, and the characteristics of infants with PNAC were analysed based on age of onset. RESULTS: PNAC was observed in 53 (13.2%) of 403 infants who survived and completed follow-up and was associated with significantly lower gestational age, birth weight, and adverse neonatal outcomes. PNAC started at a median 32 (interquartile range 23-47) days, PN was applied for 53 (34.5-64.5) days, the maximum direct bilirubin (DB) was observed at 63 (50-76) postnatal days, and PNAC resolved at 94 (79-122) postnatal days postnatal age. PNAC lasted 61 (38-89.5) days. AST and ALT normalised at 111 (100.3-142.0) and 109.5 (97-161.3) postnatal days. Infants with early-onset PNAC had significantly longer PN duration, higher maximum DB, and higher maximum AST than those with late-onset PNAC. CONCLUSION: Elevated DB, AST, and ALT persist for a long period after discontinuing PN. We suggest a cautious approach that involves waiting and reducing the frequency of additional repetitive examinations.

Fractionated Bilirubin Among 252 892 Utah Newborns with and Without Biliary Atresia: A 15-year Historical Birth Cohort Study.

OBJECTIVES: To determine whether neonatal conjugated or direct bilirubin levels were elevated in infants with biliary atresia (BA) and to estimate the number of newborns who would have positive screens in the nursery necessitating repeat testing after discharge. STUDY DESIGN: We used administrative data from a large integrated healthcare network in Utah to identify newborns who had a fractionated bilirubin recorded during birth admission from 2005 through 2019. Elevated conjugated bilirubin was defined as greater than 0.2 mg/dL and direct bilirubin was defined as greater than 0.5 mg/dL (>97.5th percentile for the assays). We performed simulations to estimate the anticipated number of false-positive screens. RESULTS: There were 32 cases of BA and 468 161 live births during the study period (1/14 700). There were 252 892 newborns with fractionated bilirubin assessed, including 26 of those subsequently confirmed to have BA. Conjugated or direct bilirubin was elevated in all 26 infants with BA and an additional 3246 newborns (1.3%) without BA. Simulated data suggest 9-21 per 1000 screened newborns will have an elevated conjugated or direct bilirubin using laboratory-based thresholds for a positive screen. Screening characteristics improved with higher thresholds without increasing false-negative tests. CONCLUSIONS: This study validates the previous findings that conjugated or direct bilirubin are elevated in the newborn period in patients with BA. A higher threshold for conjugated bilirubin improved screening performance. Future studies are warranted to determine the optimal screening test for BA and to assess the effectiveness and cost-effectiveness of implementing such a program.

Cost-Effectiveness Analysis of Universal Screening for Biliary Atresia in Japan.

OBJECTIVE: To evaluate the cost-effectiveness of universal newborn screening using stool color card or direct bilirubin (DB) testing when comparing with no screening for biliary atresia in Japanese setting. STUDY DESIGN: A decision analytic Markov microsimulation model was developed to evaluate the universal screening for biliary atresia. Our screening strategies included stool color card, DB, or no screening. The outcomes of all newborns undergoing 3 strategies were simulated to analyze event-free life-years defined as liver transplant-free survival, costs, and incremental cost-effectiveness ratio (ICER) over a 25-year period with an annual discount rate of 2% applied for both costs and outcomes. A 1-way sensitivity analysis was performed to assess the uncertainty. RESULTS: There were 941 000 newborn infants in our cohort and 114 cases of biliary atresia. The base case analysis showed that the stool color card strategy was $14 927 337 higher than no screening with an increase in 44 more event-free life-years gained, resulting in an ICER of $339 258 per event-free life-year gained. The DB screening strategy compared with stool color card was $138 994 060 higher with an increase in 271 more event-free life-years gained and an ICER of $512 893 per event-free life-year gained. The DB screening strategy compared with no screening resulted in an ICER of $488 639 per event-free life-year gained. The DB screening resulted in 16 fewer liver transplants than stool color card and stool color card had 2 fewer liver transplants than no screening. CONCLUSIONS: Universal screening for biliary atresia could be cost-effective depending on the willingness to pay thresholds for health benefits.

Mildly elevated serum bilirubin and its correlations with lipid levels among male patients undergoing health checkups.

BACKGROUND: Bilirubin's ability to lower lipid levels was confirmed by several studies, but those studies mainly focused on total bilirubin (TBil). The present study aimed to elucidate the correlations of the two subtypes of bilirubin with lipid levels. METHODS: A total of 1732 male patients undergoing health checkups were categorized into three groups according to the levels of direct bilirubin (DBil) and indirect bilirubin (IBil). The differences in medical characteristics among the three groups were analysed. RESULTS: Subjects in the elevated DBil group had the lowest serum alanine aminotransferase (ALT), total cholesterol (TC), blood urea nitrogen (BUN), γ-glutamyl transpeptidase (γ-GT), fasting blood glucose (FBG), haemoglobin (HGB), and triglyceride (TG) levels in contrast to the other groups (P < 0.01), while subjects in the elevated IBil group had the highest ALT, γ-GT, BUN, serum creatinine (SCR), HGB, TC, and TG levels among the three groups (P < 0.01). DBil levels exhibited a significant negative correlation with TC (r = -0.777, P < 0.01) and TG (r = -0.397, P < 0.01) levels, while IBil levels exhibited a significant positive correlation with TC (r = 0.790, P < 0.01) and TG (r = 0.302, P < 0.01) levels. The frequencies of abnormal TC, TG, HGB and BUN levels were the lowest in the elevated DBil group, while the levels of these four variables were the highest in the elevated IBil group. Mildly elevated DBil levels were related to lower TG (OR = 0.112, 95% CI = 0.027-0.458) and TC (OR = 0.097, 95% CI = 0.013-0.700), and mildly elevated IBil levels were connected with increased TC (OR = 3.436, 95% CI = 2.398-4.924) and TG (OR = 1.636, 95% CI = 1.163-2.303). DBil was an independent protective factor against increased TC (OR = 0.702, 95% CI = 0.602-0.817, P < 0.01) and TG (OR = 0.632, 95% CI = 0.541-0.739, P < 0.01) levels, and IBil was an independent risk factors for increased TC (OR = 1.251, 95% CI = 1.176-1.331, P < 0.01). CONCLUSIONS: DBil was an independent protective factor against high TC and TG levels. IBil was an independent risk factors for elevated TC levels. The prognostic value of IBil levels warrants further attention.

Direct bilirubin: A predictor of hematoma expansion after intracerebral hemorrhage.

BACKGROUND: Previous evidence demonstrated that several biomarkers involved in the pathological process of coagulation/hemostasis dysfunction, impairment of brain vascular integrity and inflammation are associated with hematoma expansion (HE) after intracerebral hemorrhage (ICH). We aimed to explore whether there were unreported laboratory biomarkers associated with HE that were readily and commonly available in clinical practice. METHODS: We retrospectively analyzed consecutive acute ICH patients from 2012 to 2020 with admission laboratory tests and baseline and follow-up computed tomography (CT) scans. Univariate and multivariate regression analyses were used to evaluate associations between conventional laboratory indicators and HE. The results were verified in a prospective validation cohort. The relationship of candidate biomarker and 3-month outcomes was also investigated and mediation analysis was undertaken to determine causal associations among candidate biomarker, HE and outcome. RESULTS: Of 734 ICH patients, 163 (22.2%) presented HE. Among the included laboratory indicators, higher direct bilirubin (DBil) was associated with HE (adjusted odds ratio [OR] of per 1.0 µmol/L change 1.082; 95% confidence interval [CI] 1.011-1.158). DBil >5.65 µmol/L was a predictor of HE in validation cohort. Higher DBil was also associated with poor 3-month outcomes. The mediation analysis indicated that the association of higher DBil and poor outcomes was partially mediated by HE. CONCLUSIONS: DBil is a predictor of HE and poor 3-month outcomes after ICH. DBil's metabolic process and involvement in the pathological mechanism of HE are likely to contribute to the association between DBil and HE. Interventions targeting DBil to improve post-ICH prognosis may be meaningful and worthy of further exploration.

Elevated total and direct bilirubin are associated with acute complicated appendicitis: a single-center based study in Saudi Arabia.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency and up to our knowledge no previous studies have been conducted in Saudi Arabia particularly at Qassim region and this study aimed to determine a total and direct bilirubin as a predictor of acute complicated appendicitis. METHODS: Observational retrospective study that included patients admitted under the general surgery department with a diagnosis of acute appendicitis at King Saud Hospital, Unaizah, Saudi Arabia. Data on age, gender, BMI, diabetes mellitus, total and direct bilirubin, AST, ALT, sodium, and WBCs levels were obtained. RESULT: Among the overall study population of 158 patients, the age median [IQR] was 24.5 [19-31], males were 99 (62.7%), and complicated appendicitis was 33 (20.9%). The multivariable analysis revealed that both elevated total and direct bilirubin are associated with complicated appendicitis (aOR = 3.79, 95% CI: 1.67-8.48, P = 0.001) and (aOR = 4.74, 95% CI: 2.07-10.86, P < 0.001) respectively. A receiver operating characteristic curve showed the best cutoff value of total and direct bilirubin as ≥ 15 µmol/L and ≥ 5 µmol/L respectively, with a sensitivity of 57.6%, and specificity of 73.6% for elevated total bilirubin, and a sensitivity of 54.6%, and specificity of 80% for elevated direct bilirubin. CONCLUSION: Elevated total and direct bilirubin are associated with acute complicated appendicitis in this setting. However, it should be supportive factor for acute complicated appendicitis and not considered as standalone diagnostic test.

Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults.

OBJECTVIES: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). METHODS: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method. RESULTS: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries. CONCLUSIONS: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

Elevated serum bilirubin may significantly reduce coronary heart disease risk in females: A prospective cohort study.

BACKGROUND AND AIMS: There is still inconsistent evidence over the protective effect of total bilirubin on the development of coronary heart disease (CHD). Therefore, we aimed to investigate the association between bilirubin in population subtypes and the risks of CHD between different gender and menstruation subgroups. METHODS AND RESULTS: In this prospective cohort study, 29,750 participants free of CHD with an average age of 47 ± 14 years were recruited at baseline; of these, 720 CHD first-attack cases were collected after 7-years of follow up. The covariate-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). The serum bilirubin concentration was quarterly stratified based on the distribution of healthy population without CHD onset. The HRs of incident CHD decreased with elevated bilirubin in females (ρ trend<0.05), but not males. In postmenopausal females, compared with the lowest quartile of total bilirubin, the adjusted HRs for the third and fourth quartiles were 0.64 (95% CI: 0.45, 0.93) and 0.59 (95% CI: 0.42, 0.86), the adjusted HRs in the third and fourth quartiles of direct bilirubin were 0.56 (0.39, 0.82) and 0.56 (0.38, 0.81), and for indirect bilirubin, corresponding HR in the highest quartile was 0.56 (0.38, 0.83). CONCLUSION: Elevated serum bilirubin was inversely associated with adjusted HRs of CHD in females, especially postmenopausal females. The relationship between elevated direct bilirubin and reduced HRs of CHD may be closer than indirect bilirubin in postmenopausal females.

Direct Bilirubin in Drainage Fluid 3 days after Hepatectomy Is Useful for Detecting Severe Bile Leakage.

INTRODUCTION: The International Study Group of Liver Surgery (ISGLS) definition of bile leakage is an elevated total bilirubin concentration in the drainage fluid after post-operative day (POD) 3, which has been widely accepted. However, there were no reports about direct bilirubin in drainage fluid to predict bile leakage. METHODS: Data from 257 patients who underwent hepatectomy were retrospectively reviewed. The optimal cut-off value was investigated using receiver-operating characteristic curves. The predictive power of drainage fluid total bilirubin (dTB) and drainage fluid direct bilirubin (dDB) to predict bile leakage, which was defined using ISGLS grade B or grade C, were compared. RESULTS: ISGLS grade B bile leakage occurred in 16 patients (6.2%). Area under the curve (AUC) of dDB was always higher than that of dTB on each POD. The AUC of dDB was >0.75 on PODs 2, 3, and 5, and then it increased with the increasing POD. The dDB on POD 5 showed the highest accuracy (0.91) and positive predictive value (PPV) (0.67), which was followed by dTB/serum total bilirubin (sTB) on POD 3 (accuracy, 0.91; PPV, 0.33). Because the PPV of dDB increased as the POD increased, dDB was better than dTB for predicting clinically significant bile leakage. dDB on POD 3 showed the highest negative predictive value (0.97). The positive likelihood of dDB increased and the negative likelihood of dDB decreased on the basis of the POD. Among patients with dTB/sTB ≤3 on POD 3, 19.1% of these patients had bile leakage when dDB was >0.44 on POD 3. CONCLUSIONS: Measurement of both dDB and dTB, which are easy to perform, can be used to effectively predict clinically significant bile leakage.

Association of liver abnormalities with in-hospital mortality in patients with COVID-19.

BACKGROUND & AIMS: The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. METHODS: This large retrospective cohort study included 2,073 patients with coronavirus disease 2019 (COVID-19) and definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted, with associated factors and risk of death determined by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19, with and without hepatitis B, were compared after 1:3 propensity score matching. RESULTS: Of the 2,073 patients, 1,282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of aspartate aminotransferase (AST) and direct bilirubin (D-Bil) increased early after symptom onset in deceased patients and showed disparity compared to levels in discharged patients throughout the clinical course of the disease. Abnormal AST (adjusted hazard ratio [HR] 1.39; 95% CI 1.04-1.86, p = 0.027) and D-Bil (adjusted HR 1.66; 95% CI 1.22-2.26; p = 0.001) levels at admission were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes. CONCLUSIONS: Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19-related mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, is necessary in hospitalized patients with COVID-19. LAY SUMMARY: Liver test abnormalities (in particular elevations in the levels of aspartate aminotransferase [AST] and direct bilirubin [D-Bil]) were observed after symptom onset in patients who went on to die of coronavirus disease 2019 (COVID-19). Abnormal levels of AST and D-Bil at admission were independent predictors of COVID-19-related mortality. HBV infection in patients did not increase the risk of poor COVID-19-associated outcomes.

An effective enzymatic assay for pH selectively measuring direct and total bilirubin concentration by using of CotA.

In this study, we aimed to develop B. subtilis spore coat protein A (CotA) for the enzymatic determination of bilirubin. Firstly, molecular docking and oxidation kinetic analysis confirmed the feasibility of CotA for oxidizing bilirubin. Secondly, CotA showed pH-preferable oxidization performance to direct bilirubin (DB) in acidic conditions and an alkaline-catalytic oxidation capacity to total bilirubin (TB). Mechanism analysis results confirm that the conformational changes of CotA, DB and UB caused by pH changes are responsible for the selective oxidation of DB and TB by CotA. Then, CotA exhibits better structural characteristics and enzymatic performance than M. verrucaria-derived bilirubin oxidase (Mv-BOD). Besides, the strong anti-interference ability helps CotA adapt to complex catalytic environment in the detection of DB and TB. Our results prove that CotA can be used as a promising candidate bio-enzymatic detection reagent for DB and TB.

A nomogram based on pretreatment levels of serum bilirubin and total bile acid levels predicts survival in colorectal cancer patients.

BACKGROUND: Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC). METHODS: A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS). RESULTS: DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299-0.637, P < 0.001; HR: 0.436, 95% CI: 0.329-0.578, P < 0.001; HR: 0.206, 95% CI: 0.124-0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391-0.871, P = 0.008; HR:0.437,95% CI: 0.292-0.655, P <0.001; HR: 0.634, 95% CI: 0.465-0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806-0.832) and 0.835 (95% CI: 0.822-0.849), respectively. CONCLUSIONS: TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients.

Newborn Screening for Biliary Atresia: a Review of Current Methods.

PURPOSE OF REVIEW: Biliary atresia is a serious neonatal liver disease due to obstructed bile ducts that has better outcomes when detected and treated in the first 30-45 days of life. This review examines different methods to screen newborns for biliary atresia as well as discusses observations from ongoing screening programs implemented in parts of the United States. RECENT FINDINGS: Screening strategies for biliary atresia include detecting persistent jaundice, examining stool color, testing fractionated bilirubin levels, or measuring bile acid levels from dried blood spot cards. The stool color card program is the most widely used screening strategy worldwide. An alternative approach under investigation in the United States measures fractionated bilirubin levels, which are abnormal in newborns with biliary atresia. Fractionated bilirubin screening programs require laboratories to derive reference ranges, nurseries to implement universal testing, and healthcare systems to develop infrastructure that identifies and acts upon abnormal results. Biliary atresia meets the disease-specific criteria for newborn screening. Current studies focus on developing a strategy which also meets all test-specific criteria. Such a strategy, if implemented uniformly, has the potential to accelerate treatment and reduce biliary atresia's large liver transplant burden.

[C-reactive protein and direct bilirubin as the early diagnostic indicators of primary hepatocellular carcinoma combined with macrovascular invasion].

Objective: To explore the early clinical diagnostic indicators in patients with primary hepatocellular carcinoma (HCC) combined with macrovascular invasion. Methods: The clinical data of 180 cases of HCC diagnosed by histopathology examination in the Second Affiliated Hospital of Chongqing Medical University from 2012 to 2019 were retrospectively analyzed. The factors influencing the development of macrovascular invasion in HCC patients were analyzed. The receiver operating characteristic curve (ROC curve) was used to evaluate the sensitivity and specificity. Results: Serum C-reactive protein (CRP) level was significantly correlated with various clinical characteristics of HCC patients, including the maximum tumor diameter, tumor number, and macrovascular invasion. Further analysis of the risk factors showed that serum direct bilirubin and CRP were independent risk factors for macrovascular invasion in HCC patients, with odds ratios of 1.747 (95% CI 1.119-2.728, P = 0.014) and 2.376 (95% CI 1.495-3.775, P < 0.001). ROC curve analysis showed that serum CRP, direct bilirubin, and the combination of the both had certain diagnostic value for hepatocellular carcinoma combined with macrovascular invasion. The area under the curve, sensitivity and specificity was 0.724, 0.668, 0.743, 79.1%, 70.1%, 79.1%, and 61.9%, 62.8%, 67.3%, respectively. Conclusion: The combination of CRP with direct bilirubin can be used as an important clinical diagnostic indicator for early diagnosis and prevention of hepatocellular carcinoma combined with macrovascular invasion.

Direct bilirubin is associated with low-density lipoprotein subfractions and particle size in overweight and centrally obese women.

BACKGROUND AND AIMS: Bilirubin has antioxidant and anti-inflammatory properties; serum bilirubin levels have been known to be inversely associated with cardiovascular disease. However, the effects of different bilirubin subtypes on cardiometabolic traits are unknown. In this study, we aimed to determine whether direct bilirubin is more strongly correlated with small, dense low-density lipoprotein (sdLDL) compared to other bilirubin subtypes. We also investigated which LDL subfractions exhibited the highest correlation with direct bilirubin. METHODS AND RESULTS: A total of 288 overweight and centrally obese women were included in this study. The Pearson correlation and Steiger's Z test were used to compare the correlation coefficients between bilirubin subtypes and lipoproteins. Multiple linear regression analyses were used to evaluate the independent association between direct bilirubin and mean LDL particle size. Only direct bilirubin levels were significantly associated with the sdLDL subfraction and mean LDL particle size. Mean LDL particle size exhibited a significantly stronger correlation with direct bilirubin than sdLDL, percent sdLDL, and the sdLDL:large LDL ratio. Regression analysis showed that direct bilirubin was significantly associated with mean LDL particle size, according to both the stepwise method (ß = 11.445, P value = 0.002) and the enter method (ß = 11.655, P value = 0.002). CONCLUSIONS: Direct bilirubin is more strongly correlated with the sdLDL subfraction compared with total and indirect bilirubin, and is independently associated with mean LDL particle size in overweight and centrally obese women.

Detecting paraprotein interference on a direct bilirubin assay by reviewing the photometric reaction data.

BACKGROUND: The direct bilirubin (D-Bil) assay on the AU Beckman Coulter instrumentation can be interfered by paraproteins, which may result in spurious D-Bil results. In a previous work, we took advantage of this fact to detect this interference, thus helping with the identification of patients with unsuspected monoclonal gammopathies. In this work, we investigate the possibility to detect interference based on the review of the photometric reactions, regardless of the D-Bil result. METHODS: The D-Bil assay was carried out in a set of 2164 samples. It included a group of 164 samples with paraproteins (67 of which caused interference on the assay), as well as different groups of samples for which high absorbance background readings could also be expected (i.e. hemolyzed, lipemic, or icteric samples). Photometric reaction data were reviewed and receiver operating characteristics (ROC) curves were used to establish a cut-off for absorbance that best discriminates interference. RESULTS: The best cut-off was 0.0100 for the absorbance at the first photometric point of the complementary wavelength in the blank cuvette. Once the optimal cut-off for probable interference was selected, all samples analyzed in our laboratory that provided absorbance values above this cut-off were further investigated to try to discover paraproteins. During a period of 6 months, we detected 44 samples containing paraproteins, five of which belonged to patients with non-diagnosed monoclonal gammopathies. CONCLUSIONS: Review of the photometric reaction data permits the systematic detection of paraprotein interference on the D-Bil AU assay, even for samples for which reasonable results are obtained.

Resolution of liver disease in transient abnormal myelopoiesis with fish oil emulsion.

Neonates with Down syndrome are at risk of developing transient abnormal myelopoiesis (TAM), which is characterized by transient clonal myeloproliferation of the blast cells. TAM can resolve spontaneously, but some patients die at an early age due to organ failure. Liver fibrosis in TAM is a life-threatening condition, but treatment options have not yet been established. Here, we report on the case of an infant with TAM complicated by liver disease, whose hyperbilirubinemia was successfully ameliorated with omega-3 fatty acid (ω3FA) lipid emulsion. Timely ω3FA lipid emulsion may be a feasible treatment for liver disease in TAM before serious liver damage develops.