Bilirubin-albumin Ratio Research Articles

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

Intravenous immunoglobulin in hemolytic disease of the newborn: A moving target in time.

Alloimmune hemolytic disease of the newborn (AIHDN) results in hemolysis, anemia, hyperbilirubinemia with the potential for brain damage. Intravenous immunoglobulin (IVIG) has been investigated as an alternative low-risk procedure for the treatment of AIHDN in addition to traditional treatment methods such as phototherapy and exchange transfusion (ET). To evaluate the effectiveness of IVIG therapy in decreasing ET needs based on risk factors and clinical outcomes. Charts of neonates born >30 weeks of gestation who underwent phototherapy and were administered IVIG therapy due to AIHDN between January 2013 and July 2018 were retrospectively reviewed. Sixty-three neonates were included in our study. Forty-three of them (68.3) % were full-term infants. ABO incompatibility (n = 33, 52.4%) was the major cause of AIHDN (n = 63). Additional risk factors for jaundice were found to coexist in 95.2% (n = 60) of the infants. Fifteen infants (23.8%) required ET, mostly due to Rh incompatibility (n = 11, 73.3%). Mortality was observed in 3.2% (n = 2) of the patients, 1.6% (n = 1) of whom were related to ET. Serum albumin value was found to be negatively correlated with the requirement for ET (r = 0.713, P < 0.001), whereas serum bilirubin albumin ratio was positively correlated (r = 0.489, _P < 0.001). Nine (14.3%) infants needed a simple transfusion during the hospitalization period, whereas five (7.9%) infants had readmission for simple transfusion after discharge. Apnea was the only complication seen in one (1.6%) patient. IVIG treatment should be considered due to its relative benefits when compared to exchange transfusion. In addition to its safety, it is a less complicated treatment modality with low side effect rates. It may be justified for elective use in neonates suffering from AIHDN, who will require ET with a risk of mortality by decreasing the peak of total serum bilirubin levels.

Risk factors for early hyperbilirubinemia in neonates: A cross-sectional study

Background: Neonatal hyperbilirubinemia is a commonly encountered problem in the early neonatal period. Hence, this study was undertaken in babies with significant hyperbilirubinemia to find out the factors which had caused an early rise of bilirubin (≤48 h) in some neonates compared to those who develop hyperbilirubinemia by 72 h. Factors that can predict early hyperbilirubinemia will help in early intervention.Methodology: This cross-sectional study was conducted in the neonatal intensive care unit of a tertiary care center from March 2021 to January 2022 among 405 healthy term neonates with significant hyperbilirubinemia. Serum bilirubin values were routinely done at 72 h, and earlier at 48 h if clinical icterus was noted by Kramer's rule and divided into two groups – one with hyperbilirubinemia at 48 h and another with hyperbilirubinemia by 72 h. Statistical analysis was done to find out the factors which could predict early hyperbilirubinemia.Results: Of the 405 neonates with significant hyperbilirubinemia, 270 (66.6%) had early hyperbilirubinemia and 135 (33.3%) had hyperbilirubinemia by 72 h. There were no statistically significant differences between the two groups with respect to sex, birth weight, mode of delivery, and baby blood group. Forty-two (49.4%) neonates with umbilical cord bilirubin (UCB) <2 mg/dl, 113 (65.6%) with UCB 2–2.5 mg/dl, 75 (72.1%) with UCB 2.5–3 mg/dl, 34 (89.5%) with UCB 3–3.5 mg/dl, and 6 (100%) with UCB >3.5 mg/dl developed early hyperbilirubinemia. Sixty-four (79%) neonates with bilirubin–albumin ratio (BAR) ≥0.79 developed early hyperbilirubinemia compared to 206 (63.6%) neonates with BAR <0.79 who had early hyperbilirubinemia.Conclusions: The UCB and bilirubin–albumin ratio correlated well with the development of early hyperbilirubinemia. Hence, it was concluded that those babies with a high UCB >2.1 mg/dl and/or high BAR ≥0.79 should be screened early for the development of hyperbilirubinemia.

Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy

Background and Aim: Hepatic encephalopathy (HE) is a neurological disease caused by severe liver disease. Early identification of the risk factor is beneficial to the prevention and treatment of HE. Free bilirubin has always been considered to be the culprit of neonatal kernicterus, but there is no research to explore its role in HE. In this study, we aim to study the clinical significance of the indirect bilirubin-albumin ratio in HE.Methods: A retrospective case-control study of 204 patients with liver failure was conducted. Human serum albumin (HSA) or heme oxygenase-1 (HO-1) inhibitor SnPP (Tin protoporphyrin IX dichloride) was injected intraperitoneally into Ugt1−/− mice to establish a treatment model for endogenous hyperbilirubinemia.Results: IBil/albumin ratio (OR = 1.626, 95% CI1.323–2.000, P < 0.001), white blood cell (WBC) (OR = 1.128, 95% CI 1.009–1.262, P = 0.035), ammonia (OR = 1.010, 95% CI 1.001–1.019, P = 0.027), platelet (OR=1.008, 95% CI 1.001–1.016, P = 0.022), Hb (OR = 0.977, 95% CI 0.961–0.994, P = 0.007), and PTA (OR = 0.960, 95% CI 0.933–0.987, P = 0.005) were independent factors of HE. Patients with a history of liver cirrhosis and severe HE (OR = 12.323, 95% CI 3.278–47.076, P < 0.001) were more likely to die during hospitalization. HSA or SnPP treatment improved cerebellum development and reduced apoptosis of cerebellum cells.Conclusion: The IBil/albumin ratio constitutes the most powerful risk factor in the occurrence of HE, and reducing free bilirubin may be a new strategy for HE treatment.

Comparison of Umbilical Cord blood Bilirubin (UCB) and Bilirubin Albumin Ratio (BAR) in Predicting Neonatal Hyperbilirubinemia: A Prospective Observational Study

Introduction: Hyperbilirubinemia is a commonly encountered medical condition in neonates. It becomes problematic when the levels of bilirubin raises to abnormally high values leading on to neurological problems. Bilirubin Albumin Ratio (BAR) can be used as a prediction tool for subsequent hyperbilirubinemia in neonates thereby helping in early institution of therapy. Aim: To compare Umbilical Cord blood Bilirubin (UCB) and the BAR in predicting neonatal hyperbilirubinemia. Materials and Methods: This prospective observational study was conducted in the neonates born at Al-Azhar Medical College, Thodupuzha, Kerala, India, from April 2020 to February 2021. After obtaining clearance from Institute Research Committee and Institute Ethical Committee, 1025 healthy term babies were included in the study. After an informed consent from either of the parent, cord blood was sent for bilirubin, albumin and the blood group estimation. Babies were examined daily for any development of jaundice for five days or till discharge. Venous blood was sent for bilirubin estimation if clinical icterus was noted by Kramer’s rule any time after birth or at 72 hours. If hyperbilirubinemia was detected, treatment was instituted. Two cut-offs for UCB-2 and 2.5 mg/dL and two cut-offs for BAR 0.59 and 0.69 were correlated with the neonatal hyperbilirubinemia using Pearson correlation and Chi-square test. The p-value &lt;0.05 was taken as statistically significant. The cut-off values for cord bilirubin and BAR that could predict hyperbilirubinemia was also obtained from Receiver Operating Curve (ROC). Results: Of the 1025 babies studied, hyperbilirubinemia was detected in 246 babies (24%). Babies with higher UCB and BAR had statistically significant risk of neonatal hyperbilirubinemia. UCB &gt;2 mg/dL and 2.5 mg/dL and BAR 0.59 and 0.69 were found to strongly correlate with the risk of hyperbilirubinemia. Higher the UCB and BAR, higher the risk. On ROC analysis, cut-off points for UCB and BAR were 2 mg/dL and BAR &gt;0.59 respectively. A highly significant correlation was found between UCB and hyperbilirubinemia as well as between BAR and hyperbilirubinemia with a p-value &lt;0.001. Among UCB and BAR, UCB is found to have better sensitivity and specificity than BAR with cut-off 2 mg/dL with better sensitivity of 75.2% and cut-off 2.5 mg/dL with a better specificity of 89.6%. Conclusion: UCB and BAR are strong predictors of neonatal hyperbilirubinemia with UCB a better predictor than BAR.

Early prediction of adverse outcomes in infants with acute bilirubin encephalopathy.

ObjectiveAcute bilirubin encephalopathy (ABE) remains one of the important causes of neonatal mortality and child disability, early identification, and intervention which could improve outcomes. The purpose of this study was to evaluate early predictors of adverse outcomes in infants with ABE.MethodsNewborns of gestational age ≥ 35 weeks and diagnosed with ABE were included in the study. Bilirubin‐induced neurological dysfunction (BIND) score, total serum bilirubin (TSB) peak value, and serum albumin levels were determined. Adverse outcomes were defined as death or survival with auditory dysfunction and/or cerebral palsy.ResultsEighty‐two infants were eligible for recruitment in the study. The outcome data from 76 ABE infants (92%) were used for analysis, of which 25 infants got adverse outcomes and 51 live a normal life. Univariate analysis for BIND score, TSB peak value, bilirubin–albumin ratio (B/A), albumin level, abnormal AABR, and neonatal sepsis was performed to elucidate the association with adverse outcomes. Bivariate logistic regression analysis showed B/A (OR 10.48, 95%CI: 1.55–70.81, P = 0.02) and BIND score (OR 3.68, 95%CI: 1.39–9.72, P = 0.01) were correlated with adverse outcomes. ROC curve analysis showed that B/A (≥8.9 mg/g), BIND score (≥6) could predict adverse outcomes of ABE separately; B/A in conjunction with BIND score could increase prediction sensitivity to 100%.InterpretationBoth B/A and BIND score can be used to predict adverse outcomes of ABE, and the combination of the two parameters can increase prediction sensitivity significantly.

Increased serum total bilirubin-albumin ratio was associated with bilirubin encephalopathy in neonates.

We performed the present study to summarize the recent epidemiological characteristics of bilirubin encephalopathy and assess the role of total bilirubin-albumin ratio in the bilirubin encephalopathy. We retrospectively collected clinical data of 669 neonates with hyperbilirubinemia from the First Affiliated Hospital of Zhengzhou University between January 2015 and July 2018, including 153 neonates belonged to bilirubin encephalopathy and 516 ones were treated as control group. Compared with the control group, those with bilirubin encephalopathy have higher bilirubin-albumin ratio (13.8 ± 3.6 vs. 10.6 ± 2.5, P=0.000). The direct bilirubin and indirect bilirubin level were higher in the case group than that in the control group (P=0.000). On the contrary, the hemoglobin level was lower in the case group than that in the control group (P=0.004). There were no significant differences in gestational age (P=0.510), gender rate (P=0.313), maternal gestational diabetes ratio (P=0.071), natural childbirth ratio (P=0.686), and meconium delay (P=0.091). The results from univariate regression indicated the total bilirubin/albumin ratio was positively associated with bilirubin encephalopathy (odds ratio (OR) = 1.67, 95% confidence interval (CI): 1.59–3.14). The total bilirubin, direct bilirubin, and indirect bilirubin were also related to encephalopathy. After adjusting some potential cofounding factors, the total bilirubin-albumin was still associated with bilirubin encephalopathy. The higher total bilirubin-albumin ratio increased the risk of bilirubin encephalopathy by 23% (OR = 1.23, 95% CI: 1.16–2.48). Our results indicated that the bilirubin-albumin ratio is associated with bilirubin encephalopathy in neonates, and could be a potential predictor.

Use of serum bilirubin/albumin ratio for early prediction of bilirubin induced neurological dysfunction

BackgroundKernicterus or bilirubin encephalopathy is a preventable cause of handicap, still occurs in our country. The aim of the current study was to assess the role of bilirubin/albumin ratio in improving the morbidity of the cases with unconjugated hyperbilirubinemia and to estimate of the cutoff value for B/A ratio for prevention and early management of bilirubin-induced neurological dysfunction.ResultsThe mean gestational age was 37.1 ± 2.11 weeks; the mean age of onset of jaundice was 2.36 ± 1.04 days; the mean level of total bilirubin was 26.14 ± 7.36 mg/dl. At chosen cutoff value of bilirubin albumin ratio (B/A) 6.68, sensitivity was 82% while specificity was 64% and accuracy was 95%.ConclusionBilirubin encephalopathy still occurs in significant number in our country though it is a preventable cause of handicapping. TSB is a sensitive but not a specific indicator of ABE, B/A ratio is more specific indicator of the neurologic outcome and should be utilized in the decision of early intervention.

Comparison of cord bilirubin and bilirubin albumin ratio to predict significant hyperbilirubinemia in healthy full-term neonates

Background: Early prediction and identification of severe hyperbilirubinemia for that age and appropriate treatment are must to prevent kernicterus. Objective: The objective is to study the predictive value of bilirubin albumin ratio (BAR) and to compare it with cord bilirubin alone for early identification of significant neonatal hyperbilirubinemia in healthy term neonates. Materials and Methods: This prospective cross-sectional study was done in a tertiary care center located in Central India on 543 healthy term neonates. Cord blood of 2 ml was collected during the delivery from the placental end and sent for BAR and cord bilirubin analysis. All the neonates had undergone total serum bilirubin estimation and neonates with serum bilirubin ≥17 mg/dl at ≥72 h of age were defined to have significant hyperbilirubinemia. Results: Among the study population, 44 neonates developed significant hyperbilirubinemia. Sensitivity and specificity of cord BAR were 95.45% and 89.78%. Sensitivity and specificity of cord blood bilirubin were 95.65% and 95.57%. Positive predictive value (PPV) and negative predictive value (NPV) of cord BAR were 45.16% and 99.55%. PPV and NPV of cord blood bilirubin were 64.70% and 99.58%. Considering mean as the cutoff value, cutoff value for cord BAR was 0.89 and it was 2.95 for cord blood bilirubin. Diagnostic accuracy of cord BAR and cord blood bilirubin in predicting the hyperbilirubinemia was 90.79% and 96.31%, respectively. Conclusion: Both cord BAR and cord blood bilirubin are the early predictors of neonatal significant hyperbilirubinemia, but cord blood bilirubin is the better diagnostic tool than the former in early detection of neonatal jaundice.

The bilirubin albumin ratio in the management of hyperbilirubinemia in preterm infants to improve neurodevelopmental outcome: a randomized controlled trial--BARTrial.

Background and ObjectiveHigh bilirubin/albumin (B/A) ratios increase the risk of bilirubin neurotoxicity. The B/A ratio may be a valuable measure, in addition to the total serum bilirubin (TSB), in the management of hyperbilirubinemia. We aimed to assess whether the additional use of B/A ratios in the management of hyperbilirubinemia in preterm infants improved neurodevelopmental outcome.MethodsIn a prospective, randomized controlled trial, 615 preterm infants of 32 weeks' gestation or less were randomly assigned to treatment based on either B/A ratio and TSB thresholds (consensus-based), whichever threshold was crossed first, or on the TSB thresholds only. The primary outcome was neurodevelopment at 18 to 24 months' corrected age as assessed with the Bayley Scales of Infant Development III by investigators unaware of treatment allocation. Secondary outcomes included complications of preterm birth and death.ResultsComposite motor (100±13 vs. 101±12) and cognitive (101±12 vs. 101±11) scores did not differ between the B/A ratio and TSB groups. Demographic characteristics, maximal TSB levels, B/A ratios, and other secondary outcomes were similar. The rates of death and/or severe neurodevelopmental impairment for the B/A ratio versus TSB groups were 15.4% versus 15.5% (P = 1.0) and 2.8% versus 1.4% (P = 0.62) for birth weights ≤1000 g and 1.8% versus 5.8% (P = 0.03) and 4.1% versus 2.0% (P = 0.26) for birth weights of >1000 g.ConclusionsThe additional use of B/A ratio in the management of hyperbilirubinemia in preterm infants did not improve their neurodevelopmental outcome.Trial RegistrationControlled-Trials.com ISRCTN74465643

Increased bilirubin following fluid resuscitation with albumin: mechanisms behind an important observation

Dear Editor, We read with great interest the recent study of albumin versus saline in patients with sepsis from the SAFE study investigators [1]. We were especially interested to note that in septic patients treated with albumin there was a small but significant increase in serum bilirubin leading to an increase in the liver component of the Sequential Organ Failure Assessment (SOFA) score. The authors state that this finding is likely to be due to the presence of bilirubin in the albumin solution and therefore is unlikely to represent an adverse effect of albumin administration per se. We agree that this finding does not reflect an adverse effect of albumin, but we feel the likely explanation is somewhat different. Albumin has at least two binding sites for bilirubin molecules, and the binding kinetics have been well characterised [2]. In serum the majority of bilirubin is bound to albumin with a small proportion existing in the unbound form. Current assays for bilirubin measure both fractions. The most likely explanation, therefore, for the findings by the SAFE investigators is that the total bilirubin is raised in the serum as a result of bilirubin moving from tissues to plasma in response to an increased availability of binding sites for bilirubin following albumin administration. The importance of the albumin binding sites has been investigated in vitro, and this property is exploited clinically by the molecular adsorbent recirculating system (MARS) [3]. The same investigators noticed an increase in serum bilirubin levels following administration of intravenous albumin during abdominal paracentesis, but the bilirubin/albumin ratio (BAR) remained unchanged. Lee et al. [4] observed that pre-treatment BAR is an important factor in predicting the efficacy of MARS. This mechanism may have relevance in clinical situations where scores that use bilirubin such as Child-Pugh, Model for End-Stage Liver Disease (MELD) and SOFA are used to estimate prognosis. Their prognostic ability may be improved by using BAR rather than bilirubin. Clinicians should be aware of this phenomenon not only in patients with liver disease but also in intensive treatment unit (ITU) patients with sepsis, who frequently have liver test dysfunction [5], and where use of albumin as resuscitation fluid may cause confusion if the BAR is not calculated.

Biotin deficiency with neurologic and cutaneous manifestations but without organic aciduria

bilirubin concentrations decreased markedly and for a longer duration. The free bilirubin procedure provided additional insight into bilirubin binding by yielding the maximum molar binding capacity and the dissociation constant of our patient's serum. Despite high total bilirubin concentrations, Scatchard plots obtained by titrating bilirubin into our patient 's serum were apparently linear within the range of concentrations used (10 to 20 mg/d l above plasma values). The apparent decrease in the maximum molar binding capacity and the decrease in the dissociation constant are indications of the relatively smaller number of bilirubin binding sites needed and the increased affinity of overall binding after plasmapheresis (Table). These two changes produced the markedly lower free bilirubin at essentially the same total bilirubin concentration seen after the procedure. The rise in free bilirubin concentrations in our patient may have resulted from a concurrent small increase in total bilirubin concentration and fall in albumin concentration secondary to severe injury, with its complications and treatment. We believe that the free bilirubin determinations more adequately assessed the bilirubin-albumin equilibrium and reflected the effects of plasmapheresis more accurately than would measurements of total bilirubin. This case does not establish a critical concentration of free bilirubin that is dangerous to such a patient. Furthermore, it does not imply that the free bilirubin concentration would have a similar relation to the bilirubin-albumin ratio in a newborn infant or a patient with hyperbilirubinemia of a different cause. It does demonstrate a successful method of monitoring and lowering free bilirubin in Crigler-Najjar syndrome.

Hypoglycemia in severely affected Rh erythroblastotic infants

The known association of hyperbilirubinemia and kernicterus demands methods to determine an individual infant's risk of kernicterus. Indirect albumin dye binding methods (PSP or HBABA) have been used, yet these methods are of uncertain value. Study of bilirubin-albumin binding itself and a better understanding of factors which influence the binding are necessary to evaluate the risks of kernieterus. A Sephadex G-25 column (0.9 x 10 cm.) with 0.1M phosphate buffer was used to separate bound from unbound bilirubin in pooled cord sera, sera of individual infants, adult sera, and albumin solutions. The eluate contains the bilirubin-albumin complex, while the free bilirubin remains on the column. Addition of increasing amounts of bilirubin to the serum samples reveals binding characteristics of individual specimens. Infant sera bind significantly less bilirubln (bilirubin-albumin ratio of 0.9:t) than adult sera (1.12:1) or albumin solutions (1.5:1) at pH's slightly less than physiologic pH. At higher bilirubin-albumin ratios, free bilirubin remains on the column; yet contrary to other reports, additional binding still occurs. The method is easy, rapid, and permits study not only of factors influencing bilirubin-albumin binding but also the bilirubin binding capacity of the serum of an individual jaundiced infant.