Increase In Bilirubin Concentration Research Articles

Correlation Between Total Bilirubin, Total Bilirubin/Albumin Ratio with Disease Activity in Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory disorder with unknown etiology. Oxidative stress and immune imbalance play a critical role in the pathogenesis of rheumatoid arthritis. Bilirubin has recently been recognized as a potent antioxidant as well as an immunomodulatory agent of physiological importance. The aim of this study was to explore whether increased bilirubin concentrations are correlated with good clinical prognosis of rheumatoid arthritis. In this cross-sectional study, we included 197 healthy individuals and 197 RA patients in the Affiliated Hospital of North Sichuan Medical College from October 2020 to February 2022. The latter were classified into three classes of disease activity according to DAS28-ESR: remission and low (DAS28-ESR<3.2), moderate (3.2≤DAS28-ESR≤5.1), and high (DAS28ESR>5.1). Based on the clinical and laboratory data, we evaluated the association of bilirubin levels with disease activity in RA using multivariable ordered logistic regression. The levels of total bilirubin and total bilirubin/albumin ratio were significantly lower (P < 0.001; P < 0.001) in RA patients compared with healthy controls. In RA patients, Spearman's rank correlation analysis revealed that bilirubin and total bilirubin/albumin ratio were negatively correlated with disease activity and inflammatory marker (C-reactive protein, erythrocyte sedimentation rate, Interleukin-6). In multivariable ordered logistic regression, higher total bilirubin (OR=0.77, 95% CI: 0.67-0.89, p<0.001) independently predicted lower disease activity. Bilirubin levels remain associated with a reduction of disease activity, suggesting that bilirubin may be a protective factor for RA aggravation.

Determining the medical and biological safety of meat-containing polycomponent products based on regional raw materials

This paper reports medical and biological studies of semi­finished meat product and meat­containing semi­smoked sausage on laboratory rats. The purpose of the study was to investigate the effect of the developed products on the dynamics of live weight, the state of internal organs and tissues, general and biochemical parameters of the blood of animals when they are introduced into the standard diet in the amount of 30 %. The studies were conducted on 30 white nonlinear rats weighing 145–150 g, of which one control and two experimental groups were formed, according to the principle of the method of analog groups.It is proved that the introduction of meat­containing multicomponent products with a high protein content into the diet of rats in the amount of 30 % of the standard diet contributes to the intensification of animal growth processes. It was confirmed that the increase in live body weight of rats after 21 days of the experiment amounted to 33–38 %, which is larger than that in control by 69–90 %. No negative impact on the state of the internal organs of rats from the consumption of the developed products was detected.It was found that the inclusion of meat­containing multicomponent products in the diet of rats contributes to an increase in erythropoiesis by 12.66 % compared to the starting data. The inclusion of products in the diet does not significantly change the content of leukocytes and platelets while increasing blood saturation with hemoglobin by 45.83–58.33 % higher compared to control animals.The introduction into the diet of laboratory rats of meat­containing multicomponent products has an anabolic effect and contributes to an increase in the concentration of hemoglobin by 42.12 %, total protein by 4.79 %, creatinine by 19.68 %. In laboratory rats, there is a decrease in glucose by an average of 8.17 %, which indicates an intensification of processes in muscle tissue. Enhanced protein synthesis due to increased catabolism leads to an increase in bilirubin concentration by 19.12–21.97 % compared to control rats. Medical and biological studies of meat­containing multicomponent products can be applied in practice to confirm their safety

Jaundice in relation to immune activation during Epstein-Barr virus-induced infectious mononucleosis

BackgroundLiver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients with infectious mononucleosis and immune abnormalities associated with jaundice. MethodsWe report on an adult patient with monoclonal B lymphocytosis and IgM-lambda gammopathy who developed a severe icteric hepatitis during infectious mononucleosis. We then reviewed the clinical records of 389 patients admitted to the hospital with infectious mononucleosis between 1995 and 2018 (51.7% male patients; median age, 19 years; range, 15-87 years) with focus on liver abnormalities and associated factors. ResultsFifty-nine patients (15.1%) had serum bilirubin concentrations between 1.5 and 3 mg/dL, and 47 patients (12.0%) had serum bilirubin >3 mg/dL. Patients with increased bilirubin concentrations had a distinct clinical presentation, with more frequent abdominal pain, nausea and vomiting, and less frequent sore throat than patients with normal bilirubin. Age and sex were not significantly different for the patients with increased and normal serum bilirubin concentrations. The patients with increased serum bilirubin concentrations showed higher levels of immune activation markers than the patients with normal bilirubin, including blood lymphocyte counts, serum IgM, and β2-microglobulin concentrations. Heterophile antibody-positive patients (88.6%) showed similar bilirubin concentrations but higher aspartate aminotransferase and alkaline phosphatase levels than their heterophile-negative counterparts. Serum bilirubin elevations normalized quickly during follow-up. ConclusionsTransient hyperbilirubinemia is common during severe (in-hospital) infectious mononucleosis in adult patients. Patients with hyperbilirubinemia have less frequent pharyngitis symptoms and more frequent abdominal symptoms. Hyperbilirubinemia during infectious mononucleosis is associated with immune activation markers.

Medical and biological studies of meat polycomponent products based on regional raw materials

The article is devoted to the study of the medical and biological safety of consumption of multicomponent meat-rich semi-finished products and semi-smoked sausage. When creating functional products, the approach of multi-ingredient modeling of the future product is applied according to the principle of adding nutritional and biological value. The multi-component nature of the constituent ingredients with different chemical composition makes it possible to obtain products with specified characteristics. There is a problem of ensuring the food safety of the developed product during production, storage and consumption of finished products.&#x0D; The purpose of the study was to study the effect of the developed meat-containing polycomponent semi-finished products and semi-smoked sausage on the growth dynamics and the level of metabolic processes of experimental rats when they are introduced into the standard diets of animals in the amount of 30 %. The work was performed on 36 white non-linear rats weighing 160–200 g.&#x0D; Medical and biological studies of multicomponent meat-containing products have shown their absence of a negative effect on the growth and development of animals, the level of metabolic processes during the growth period.&#x0D; It has been established, that feeding rats with meat-rich polycomponent products in the amount of 30 % of the standard diet increases the live weight of rats by 33–38 % within 3 weeks. Anatomopathological changes in the internal organs of the experimental rats were not detected.&#x0D; The inclusion of meat-rich multicomponent products in the diet of rats promotes the strengthening of hematological processes in the body, increases the concentration of erythrocytes in the blood to 8.01±0.11·1012/l, which is 12.7 % higher, compared to the control animals, increases the hemoglobin content in erythrocytes by 45.83–58.33 % higher, compared to the control animals.&#x0D; It has been proven, that the consumption of meat-containing multicomponent products by rats leads to an increase in the concentration of total protein by 4.79 %, hemoglobin by 42.12 %, and creatinine by 19.68 %. Enhanced protein synthesis due to intensification of catabolism leads to an increase in bilirubin concentration by 19.12–21.97 % compared to the control rats

Identifying Potential Therapeutic Applications and Diagnostic Harms of Increased Bilirubin Concentrations: A Clinical and Genetic Approach.

Bilirubin has antioxidant and anti-inflammatory properties in vitro and in animal studies and protects against inflammatory, cardiovascular, and other diseases in observational studies; therefore, bilirubin has potential as a therapeutic agent. However, observational studies could be confounded by many factors. We used a genetic (n=61,281) and clinical (n=234,670) approach to define the association between bilirubin and 19 conditions with a putative protective signal in observational studies. We also tested if individuals with genetically higher bilirubin levels underwent more diagnostic tests. We used a common variant in UGT1A1 (rs6742078) associated with an 26% increase in bilirubin levels in the genetic studies. Carriers of the variant had higher bilirubin levels (P=2.2×10-16 ) but there was no significant association with any of the 19 conditions. In a phenome-wide association study (pheWAS) to seek undiscovered genetic associations, the only significant finding was increased risk of "jaundice-not of newborn." Carriers of the variant allele were more likely to undergo an abdominal ultrasound (odds ratio=1.04, [1.00-1.08], P=0.03). In contrast, clinically measured bilirubin levels were significantly associated with 15 of the 19 conditions (P<0.003) and with 431 clinical diagnoses in the pheWAS (P<1×10-5 adjusted for sex, age, and follow-up). With additional adjustment for smoking and body mass index, 7 of 19 conditions and 260 pheWAS diagnoses remained significantly associated with bilirubin levels. In conclusion, bilirubin does not protect against inflammatory or other diseases using a genetic approach; the many putative beneficial associations reported clinically are likely due to confounding.

Association of Serum Total Bilirubin Concentration with Telomere Length: The National Health and Nutrition Examination Survey.

Introduction Mildly increased bilirubin concentration has a protective effect on oxidative stress–related diseases. However, it remains unknown whether elevated circulating bilirubin is associated with longer telomere length. The aim of this cross-sectional study was to examine the association between total bilirubin concentration and telomere length. Methods We used the data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. The multivariable linear regression model was used to examine the association between total bilirubin concentration and telomere length. The nonlinear relationship was analyzed using a generalized additive model with the smoothing plot. Results A total of 7818 participants with a mean age of 49.20 ± 18.82 years were included. Compared with the lowest concentration of total bilirubin (Q1), the highest quartile of total bilirubin concentration was associated with longer telomere length in male (β = 0.04, 95 CI%: 0.00, 0.07, P = 0.024) and female (β = 0.04, 95 CI%: 0.02, 0.04, P = 0.002). Furthermore, an inverted U-shaped relationship between total bilirubin and telomere length was found. On the left of turning points (total bilirubin < 0.5 mg/dL), total bilirubin concentration was positively associated with telomere length (β = 0.23, 95 CI%: 0.14, 0.32, P < 0.001). However, the association between total bilirubin concentration and telomere length was not significant (β = 0.01, 95% CI: -0.01, 0.04, P = 0.346) above the turning point. Conclusion This is the first evidence based on a nationally representative survey demonstrating a positive and nonlinear association between total bilirubin concentration and telomere length. Future large-scale prospective studies are warranted to confirm our findings.

Comparative Study of Liver Function and Rh Blood Group between both Physiological and Pathological Neonatal Jaundice

Abstract&#x0D; Backgrounds: Jaundice occurs in most newborn due to increased bilirubin concentration. Jaundice is observed during the first week after birth in approximately 60% of term neonates. A high level of bilirubin is neurotoxic and may cause neonatal kernicterus, auditory neuropathy or death.&#x0D; Objectives: to compare the Rh group compatibility, serum bilirubin (total and direct), serum albumin and several liver enzymes between physiological and pathological neonatal jaundice&#x0D; Materials and Methods: A cross sectional study for one hundred neonates with jaundice divided into group 1: 50 newborns with physiological jaundice, Group 2: 50 newborns with pathological jaundice. Blood samples taken from each patient use to determination of Rh Group and blood group, serum bilirubin (total and direct, liver enzymes and albumin concentration. Results: in the present study Rh Compatibility show a significant relationship between newborns with physiological and pathological jaundice (p&lt;0.05). Serum bilirubin (total and direct), serum albumin concentration and several liver enzymes were significantly higher when compare newborns with pathological jaundice with newborns of physiological jaundice (p&lt;0.05).&#x0D; Conclusion: these finding demonstrate that newborns with pathological jaundice have higher concentrations of these parameters as compared with physiological jaundice .&#x0D;

On the question of the toxic effects of sulfate m-bromoaniline on the blood system

Introduction. The preclinical study of the effect of chemical intoxication on the blood system's states is especially relevant for preventing and treating workers producing bromo-aromatic compounds with polytropic toxic effects m-bromaniline sulfate, in case of possible contact at the stages of its synthesis. The aim of the study to research in an experiment the toxic effect of m-bromaniline sulfate on the state of the blood system. Materials and methods. Sulfate m-bromaniline is an intermediate of the synthesis of the drug tramadol. Scientists study the toxic effect of sulfate m-bromaniline in experiments on rats. We reproduce single inhalation and subacute intragastric modes and methods of exposure. The researchers evaluated the impact of the substance on animals based on the results of peripheral blood tests. Namely: by the number of red blood cells, hemoglobin, white blood cells, analysis of the white blood cell formula. According to the indicators of biochemical tests of blood serum, morphological data of the study of the liver, kidneys, heart, stomach. We took into account the readings of the critical parameters of the pancreas and thyroid glands. Results. The results of examining animals subjected to acute inhalation intoxication and sub-acute intragastric exposure showed the same type of changes in the peripheral blood and experimental group's biochemical profile. The intake of m-bromaniline sulfate leads to a decrease in the number of red blood cells and hemoglobin against the background of increased reticulocytosis, leukocytosis. The number of eosinophils in the blood of animals exposed to poisoning decreased by almost one and a half times. We found a violation of the balance of hemoglobin fraction's content. Also reduced oxyhemoglobin, an increase in methemoglobin. Researchers discovered in the blood sulfohemoglobin in the absence of it in the control group's animals. The animals' biochemical profile revealed increased blood catalase activity against the background of its decrease in red blood cells. In the blood serum of rats primed with sulfate m-bromaniline we found an increase in bilirubin concentration. We noted an increase in the activity of aspartate aminotransferase while maintaining the same action of alanine aminotransferase. The effect of sulfate m-bromaniline at the morphological level revealed vascular disorders in all internal organs and moderately pronounced fatty degeneration of the liver and kidneys. The spleen was hyperplastic; a large amount of brown iron-containing pigment was noted intra- and extracellularly in the red pulp. Conclusions. Different receipt methods of sulfate m-bromaniline in the conditions of acute inhalation sub-acute intragastric experiments lead to some disorders. Violations have a hemotoxic character with a predominant effect on the state of the blood system. An essential element of intoxication prevention can be the correct selection of the persons entering the work contact with toxicants. Individuals with manifesting or latent iron deficiency, various hemorrhagic syndrome types, and severe forms of autonomic dysfunction represent a health risk group if possible contact with sulfate m-bromaniline.

Relevance of Adipose Tissue Accumulation and Muscularity in Patients Undergoing Liver Resection

Introduction: Nutritional status is known to affect the quality of liver parenchyma. This study aimed to evaluate the relevance of the amount of adipose and muscular tissue assessed on computed tomography (CT) in patients undergoing liver resection. Methods: In this prospective observational study, 64 patients undergoing liver resection underwent preoperative CT assessment of height-normalized amount of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and total adipose tissue (TAT), smooth muscle (SM) and psoas muscle (PM). The primary outcome measure was early injury and function of remnant liver, as reflected by immediate (within 24 hours) and peak serum transaminases activity, international normalized ratio (INR), and bilirubin concentration. Results: Median SAT, VAT, TAT, SM, and PM were 65.4, 41.0, 115.1, 47.8, and 5.9 cm2/m2, respectively. TAT was significantly correlated with macro- (R=0.43; p=0.001) and microvesicular (R=0.36; p=0.007) liver steatosis, with stronger impact of subcutaneous than visceral fat. In patients undergoing minor resections (n=29), SM was positively correlated with early (R=0.53; p=0.004) and peak (R=0.43; p=0.020) bilirubin and SAT (R=0.43; p=0.031), VAT (R=0.51; p=0.007), and TAT (R=0.50; p=0.010) were positively correlated with early INR. Interestingly, in patients without relevant liver steatosis (< 30%), SAT (R=0.48; p=0.034) was additionally positively correlated with early aspartate transaminase activity and VAT (R=0.48; p=0.029) and TAT (R=0.55; p=0.010) with peak aspartate transaminase activity. Conclusion: Excessive amount of adipose tissue exacerbates injury and negatively influences early liver remnant function after minor liver resections. Increased muscularity may lead to increased bilirubin concentrations of undetermined clinical significance.

Determination and Identification of Bilirubin in Jaundiced Pig Liver by High Performance Liquid Chromatography

A high performance liquid chromatography (HPLC) method was developed for the determination of bilirubin concentration in pig liver. The sample was extracted by sequential extraction with dimethyl sulfoxide and acetonitrile, followed by HPLC analysis. The accuracy of the analytical method was estimated by spiking pig liver samples with three different concentrations of bilirubin (2.5, 5 and 10 μg/mL) and a recovery of 75.7 - 84.9% was obtained, with corresponding intra-day and inter-day precisions of 1.6 - 4.1% and 2.4 - 3.9%, respectively. The limit of detection of bilirubin was 0.3 μg/mL and the analytical time for one sample was 9 min. In this study, the bilirubin concentration of normal and jaundiced pig livers was determined. It was concluded that the procedure could provide scientific data for detecting increased bilirubin concentration to identify jaundiced livers. The analytical method was found to be rapid, sensitive, accurate, repeatable and reproducible, and could be applied for the measurement of bilirubin concentration in pig liver.

Bilirubin enhances the activity of ASIC channels to exacerbate neurotoxicity in neonatal hyperbilirubinemia in mice.

Neonatal hyperbilirubinemia is a common clinical condition that can lead to brain encephalopathy, particularly when concurrent with acidosis due to infection, ischemia, and hypoxia. The prevailing view is that acidosis increases the permeability of the blood-brain barrier to bilirubin and exacerbates its neurotoxicity. In this study, we found that the concentration of the cell death marker, lactate dehydrogenase (LDH) in cerebrospinal fluid (CSF), is elevated in infants with both hyperbilirubinemia and acidosis and showed stronger correlation with the severity of acidosis rather than increased bilirubin concentration. In mouse neonatal neurons, bilirubin exhibits limited toxicity but robustly potentiates the activity of acid-sensing ion channels (ASICs), resulting in increases in intracellular Ca2+ concentration, spike firings, and cell death. Furthermore, neonatal conditioning with concurrent hyperbilirubinemia and hypoxia-induced acidosis promoted long-term impairments in learning and memory and complex sensorimotor functions in vivo, which are largely attenuated in ASIC1a null mice. These findings suggest that targeting acidosis and ASICs may attenuate neonatal hyperbilirubinemia complications.

Influence of hypertriglyceridemia, hyperbilirubinemia and hemolysis on thrombin generation in human plasma.

Background Although accumulating evidence suggests that the hemostatic balance is impaired in patients with hypertriglyceridemia, hyperbilirubinemia or hemolytic anemias, little is known on the underlying biological mechanisms. This experimental study was aimed at exploring whether increasing values of triglycerides, bilirubin or cell-free hemoglobin promote thrombin generation in plasma. Methods Three different pools were prepared from three different sets of 20 normal routine plasma citrate samples. The native pools were spiked with increasing amounts of exogenous triglycerides (up to 8.8 mmol/L), bilirubin (up to 350 μmol/L) or autologous hemolyzed blood (up to 3.5 g/L cell-free hemoglobin). Using the fully-automated thrombin generation analyzer ST Genesia, we measured the following parameters: lag time (LT), time to peak (TP), peak height (PH) and endogenous thrombin potential (ETP). Results A sustained increase of PH and ETP was found in parallel with increasing triglyceride concentrations, peaking in the aliquot with 8.8 mmol/L. Conversely, LT and TP displayed an opposite trend, reaching a maximum decrease in the 8.8 mmol/L aliquot. Increasing bilirubin concentrations promoted remarkable increases of PH and ETP and decreases of TP and LT, up to 211 μmol/L. After this threshold, all parameters tended to return towards baseline values. A constant increase of PH and ETP was also noted in hemolyzed samples, peaking in the 3.5 g/L cell-free hemoglobin aliquot, whereas the TP and LT remained unchanged in all hemolyzed aliquots. Conclusions Our findings suggest that hypertriglyceridemia, hyperbilirubinemia and hemolysis may promote a hypercoagulable state in human plasma.

Association between plasma bilirubin and mortality

Introduction and aimIt has been proposed that plasma concentration of bilirubin, an endogenous antioxidant, is protective against diseases mediated by increased oxidative stress, including cardiovascular diseases (CVD) and cancer. To examine this hypothesis, we investigated the relationship between plasma bilirubin concentrations and bilirubin UDP-glucuronosyl transferase (UGT1A1) promoter gene variations (associated with increased bilirubin concentrations) with total/CVD and cancer mortality. Materials and methodsA nested case–control study was conducted within the Polish arm of the HAPIEE cohort. At baseline in 2002–2005, participants were examined in detail. Mortality follow-up (median (IQR) between blood draw and death was 3.7 (2.1–5.1) years) was performed by linkage with regional and national death registers. Plasma biomarkers were analysed in all subjects who died from any cause (cases, n=447) and in a random subsample of survivors (controls, n=1423). ResultsThere was a strong negative association between plasma bilirubin levels and total and cancer mortality, expressed more profoundly in men. The adjusted OR of deaths from all causes and cancer, comparing the highest vs. lowest plasma bilirubin categories were 0.61 (95% CI: 0.42–0.87) and 0.39 (0.24–0.65), respectively. There was no association of bilirubin with CVD mortality. The UGT1A1*28 allele, a genetic marker of raised bilirubin, was also negatively associated with total/cancer mortality, although the associations were not statistically significant. DiscussionBoth the observational and genetic associations support the negative relationship between bilirubin and total mortality; this association appears to be driven by cancer mortality, while that with CVD mortality is not evident.

Bilirubin Interference in Plasma Amino Acid Analysis by Ion Exchange Chromatography.

To evaluate the effect of bilirubin interference on plasma amino acid analysis by Ion Exchange Chromatography (IEC). Cross-sectional (method validation) study. Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from August 2016 to July 2017. Twenty non-icteric samples from paediatric patients were collected in lithium heparin tubes and analysed for amino acids on IEC-based Biochrome® 30+ Analyzer (Harvard Biosciences UK). Baseline bilirubin levels were noted. Samples were spiked with neonatal bilirubin standard with concentration of 488.4 mol/L (Spinreact®-Spain) at final concentrations of 50, 150 and 230 mol/L and re-analysed for amino acids at these three concentrations. Among the 20 selected patients with normal amino acid profiles, 12 (60%) were males. Majority (55%) were in age group of 1-5 years. Significant difference was observed for Arginine (p = 0.01), Histidine (p = 0.001), Isoleucine (p = 0.01), Leucine (p = 0.007), Lysine (p = 0.005), Ornithine (p = 0.03) and Phenylalanine (p = 0.02). Mean rank of these amino acids showed decreasing trend with the increase of bilirubin concentration, and pronounced interference was identified at bilirubin level of 50 mol/L. No difference was observed for alanine, citrulline, glutamic acid, glycine, methionine, proline, threonine, tyrosine, asparagine, aspartic acid, cystine, valine and tryptophan. Bilirubin significantly interferes with certain amino acid levels when analysis is carried out by ion exchange chromatography. A close follow-up of such patients with other biochemical tests and a repeat amino acid analysis, after jaundice is settled, is recommended to confidently rule out any possible inherited metabolic disorder in these patients.

Liver dysfunction in sepsis.

Despite continuous progress in medicine, sepsis remains the main cause of deaths in the intensive care unit. Liver failure complicating sepsis/septic shock has a significant impact on mortality in this group of patients. The pathophysiology of sepsis-associated liver dysfunction is very complicated and still not well understood. According to the Surviving Sepsis Campaign (SSC) Guidelines, the diagnosis of liver dysfunction during sepsis is based on the increase in bilirubin concentration >2 mg/dL and the occurrence of coagulation disorders with INR > 1.5. The lack of specificity and ability to distinguish acute liver failure from previous liver dysfunction disqualifies bilirubin as a single parameter reflecting the complex liver function. Clinical manifestations of sepsis-associated liver dysfunction include hypoxic hepatitis, sepsis-induced cholestasis and dysfunction of protein synthesis manifesting with, e.g., coagulopathies. Detoxifying liver dysfunction, which is associated with an increase in serum ammonia concentration, manifesting with e.g., confusion, loss of consciousness and hepatic encephalopathy, may be disguised by analgosedation used in the intensive care unit. To determine a liver dysfunction in a critically ill patient, the concept of shock liver may be used. It is a complex syndrome of hemodynamic, cellular, molecular and immunologic changes leading to severe liver hypoxia. In clinical practice, there is no standardized diagnostic panel that would allow for an early, clear diagnosis of acute liver dysfunction, and there is no therapeutic panel enabling the full restoration of damaged liver function. The aim of the article is to present the pathophysiology and clinical manifestations of sepsis-associated liver dysfunction.

Might Bilirubin Serve as a Natural Antioxidant in Response to Neonatal Encephalopathy?

Neonatal asphyxia is often associated with hepatic injury. We hypothesized that this might lead to increased bilirubin concentrations. Term neonates admitted between January 2015 and April 2017 who remained hospitalized for ≥ 4 days and who had serial serum bilirubin concentrations recorded were divided into those with neonatal encephalopathy (NE) and controls. Serial serum bilirubin concentrations during the first days of life were compared between groups. Twenty-nine neonates with NE and 84 age-matched controls were identified. Mean total serum bilirubin concentrations of NE babies were significantly lower than those controls throughout the first days of life. At 96 hours of age, NE serum bilirubin concentrations were 4.5 (3.2, 5.8) versus controls of 10.5 (9.4, 11.5) mg/dL (p < 0.0001). The mean area under the curve (AUC) for the NE group was 268 (215, 321) versus 663 (608, 718), p < 0.0001, for the control group. All of the NE babies remained below the 40th percentile of the Bhutani curve and none required phototherapy. Contrary to our hypothesis, bilirubin concentrations in NE infants are significantly lower than expected during the first 4 days postnatally. We speculate that, under conditions of severe oxidative stress, bilirubin is consumed as an antioxidant.

Toxicologic, hypoglycaemic and hypolipidemic effects of ethanolic and ether extracts of Commiphora molmol from Saudi Arabia

Ether as well as ethanol extracts of Commiphora molmol administered orally to 42 rats at a dose rate of 200, 400 and 600 mg/kg body weight/d for 2 weeks were toxic to laboratory rats. Group 1 was the control which was fed regular diet without the plant extract. Groups 2, 4 and 6 were fed ethanol extract of C. molmol at a dose rate of 200, 400 and 600 mg/kg/body weight/d respectively. Groups 3, 5 and 7 were fed ether extract of C. molmol at a dose rate of 200, 400, 600 mg/kg/body weight/d respectively. The toxic effects were exhibited in all groups by a significant decrease (p<0.05) in the body weights of the experimental rats compared to those weights of the control rats. Experimental animals showed marked depression, abdominal pain, and dyspnoea at their late stages. Haematological changes in rats fed both ether and ethanol extracts of the plant were indicated by significant decrease (p<0.05) in the RBC count as well as in the haemoglobin concentrations while there was significant increase (p<0.05) in the WBC counts. Rats which fed ether extract showed significant decrease in glucose in all groups, cholesterol and triglycerides and a significance increase in bilirubin concentration in experimental animals which fed 400 and 600 mg/body weight/d. Histological changes in experimental rats were observed in the form of fatty change and necrosis of hepatocytes, renal tubular cell degeneration, and shrinkage of the glomeruli.

Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial

REP 2139 clears circulating hepatitis B virus (HBV) surface antigen (HBsAg), enhancing the restoration of functional control of HBV infection by immunotherapy. We assessed the safety and efficacy of REP 2139 and pegylated interferon alfa-2a in patients with chronic HBV and hepatitis D virus (HDV) co-infection. In this open-label, non-randomised, phase 2 trial, patients aged 18-55 years, who were treatment naive, hepatitis B e antigen [HBeAg] negative, anti-hepatitis D antigen [HDAg] positive, and HDV RNA positive, with serum HBsAg concentrations of more than 1000 IU/mL, and a history of HDV infection for 6 months or more before treatment, were recruited at Toma Ciorbă Hospital of Infectious Diseases in Chișinău, Moldova. Patients were excluded if they had HDV superinfection, liver infections other than HBV and HDV, or liver cirrhosis. Patients received 500 mg intravenous REP 2139 once per week for 15 weeks, followed by combined therapy with 250 mg intravenous REP 2139 and 180 μg subcutaneous pegylated interferon alfa-2a once per week for 15 weeks, then monotherapy with 180 μg pegylated interferon alfa-2a once per week for 33 weeks. The primary endpoints assessed at the end of treatment were the safety and tolerability of the treatment regimen, analysed in the intention-to-treat population. Secondary outcomes included the proportion of patients with serum HBsAg less than 50 IU/mL, the proportion of patients with suppressed HBV DNA, and the proportion of patients who maintained these responses through follow-up. The REP 301 trial is registered with ClinicalTrials.gov, number NCT02233075. We also did an additional follow-up at 1 year after the end of treatment, as an interim analysis of the REP 301-LTF trial (planned duration 3 years), registered with ClinicalTrials.gov, number NCT02876419, which is ongoing but not recruiting patients. Between Sept 8, 2014, and Jan 27, 2015, we enrolled 12 patients into the REP 301 study. All 12 patients experienced at least one adverse event during treatment: two (17%) patients experienced anaemia, eight (67%) neutropenia, and ten (83%) thrombocytopenia. Five (42%) patients had raised alanine aminotransferase levels, four (33%) had raised aspartate aminotransferase levels, and two (17%) had increased bilirubin concentrations. Four (33%) patients had a serious adverse event, and 12 (100%) patients had treatment-emergent lab abnormalities. Six patients had HBsAg levels less than 50 IU/mL by the end of treatment (all <0·05 IU/mL); five maintained this level of suppression at the end of 1 year follow-up. Six patients had hepatitis B surface antibody (anti-HBs) titres above 10 mIU/mL at the end of treatment (five had maximum anti-HBs concentrations of 7681-86 532 mIU/mL during treatment), which were maintained at the end of 1 year follow-up in these five patients. Elevated alanine and aspartate aminotransferase concentrations and profound elevations of anti-HBs titres were restricted to patients who had HBsAg levels of less than <1 IU/mL before the introduction of pegylated interferon alfa-2a. Nine patients had suppressed HBV DNA (<10 IU/mL]) at the end of treatment, which was maintained by seven patients and newly established in an eighth patient at the end of 1 year follow-up. 11 patients became HDV RNA negative during treatment, with nine remaining HDV RNA negative at the end of treatment; seven of these patients remained HDV RNA negative by the end of 1 year follow-up. By the end of 1 year follow-up, normalisation of serum aminotransferases occurred in nine of 12 patients. Combined REP 2139 and pegylated interferon alfa-2a therapy is safe, well tolerated, and establishes functional control of HBV and HDV co-infection and normalisation of serum aminotransferases in a high proportion of patients 1 year after therapy. This combination therapy approach might provide a new treatment option for patients with HBV and HDV co-infection. Replicor.

Relationship between serum bilirubin concentrations and diabetic nephropathy in Shanghai Han\u2019s patients with type 1 diabetes mellitus

BackgroundRecent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM).MethodsA total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20–0.60; Q2, 0.60–0.80; Q3, 0.80–1.00; Q4, 1.00–1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM.ResultsThe median bilirubin level was 0.56 (interquartile: 0.43–0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58–0.89 mg/dL], P < 0.001). Spearman’s correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P < 0.05) and multiple stepwise regression analysis showed bilirubin concentrations were independently associated with 24 h urinary microalbumin. In logistic regression analysis, bilirubin concentrations were significantly inversely associated with nephropathy. In addition, in stratified analysis, from the first to the fourth quartile group, increased bilirubin concentrations were associated with decreased prevalence of DN from 21.90% to 2.00%.ConclusionHigh bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.

The impact of the UGT1A1*60 allele on bilirubin serum concentrations.

Identify the functional status of the uridine-diphosphate glucuronyl transferase 1A1 (UGT1A1) -3279T>G (*60) variant. Retrospective review of clinically obtained serum bilirubin concentrations in pediatric patients to evaluate the association of the UGT1A1 -3279T>G (*60) variant with bilirubin concentrations and assessed linkage disequilibrium of the UGT1A1 -3279T>G (*60) and A(TA)7TAA (*28) variants. Total bilirubin concentration did not differ between patients who had a UGT1A1*1/*1 diplotype and patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant. Total bilirubin concentration was lower in patients homozygous for the UGT1A1 -3279T>G (*60/*60) variant than in patients homozygous for the UGT1A1 A(TA)7TAA (*28/*28) variant (p < 0.01). The -3279T>G (*60) and A(TA)7TAA (*28) variants were in strong incomplete linkage disequilibrium in both black and white patients. The presence of the UGT1A1 -3279T>G (*60) variant is not associated with increased bilirubin concentrations.