Predictive value of bilirubin and serum γ-glutamyltranspeptidase levels in type-2 diabetes mellitus patients with acute coronary syndrome

BACKGROUND Cardiovascular disease is a major complication of diabetes mellitus(DM).Type-2 DM(T2DM)is associated with an increased risk of cardiovascular events and mortality,while serum biomarkers may facilitate the prediction of these outcomes.Early differential diagnosis of T2DM complicated with acute coronary syndrome(ACS)plays an important role in controlling disease progression and improving safety.AIM To investigate the correlation of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)with major adverse cardiovascular events(MACEs)in T2DM patients with ACS.METHODS The clinical data of inpatients from January 2022 to December 2022 were analyzed retrospectively.According to different conditions,they were divided into the T2DM complicated with ACS group(T2DM+ACS,n=96),simple T2DM group(T2DM,n=85),and simple ACS group(ACS,n=90).The clinical data and laboratory indices were compared among the three groups,and the correlations of serum total bilirubin(TBIL)levels and serumγ-GGT levels with other indices were discussed.T2DM+ACS patients received a 90-day follow-up after discharge and were divided into event(n=15)and nonevent(n=81)groups according to the occurrence of MACEs;Univariate and multivariate analyses were further used to screen the independent influencing factors of MACEs in patients.RESULTS The T2DM+ACS group showed higherγ-GGT,total cholesterol,low-density lipoprotein cholesterol(LDL-C)and glycosylated hemoglobin(HbA1c)and lower TBIL and high-density lipoprotein cholesterol levels than the T2DM and ACS groups(P<0.05).Based on univariate analysis,the event and nonevent groups were significantly different in age(t=3.3612,P=0.0011),TBIL level(t=3.0742,P=0.0028),γ-GGT level(t=2.6887,P=0.0085),LDL-C level(t=2.0816,P=0.0401),HbA1c level(t=2.7862,P=0.0065)and left ventricular ejection fraction(LEVF)levels(t=3.2047,P=0.0018).Multivariate logistic regression analysis further identified that TBIL level and LEVF level were protective factor for MACEs,and age andγ-GGT level were risk factors(P<0.05).CONCLUSION Serum TBIL levels are decreased andγ-GGT levels are increased in T2DM+ACS patients,and the two indices are significantly negatively correlated.TBIL andγ-GGT are independent influencing factors for MACEs in such patients.

Combined preoperative albumin bilirubin score and hepatectomy percentage for evaluate the liver regeneration after partial hepatectomy

Surgical resection is a pivotal therapeutic approach for addressing hepatic space-occupying lesions,with liver volume restoration and hepatic functional recovery being crucial for assessing surgical prognosis.The preoperative albumin-bilirubin(ALBI)score,encompassing serum albumin and bilirubin levels,can be determined via blood analysis,effectively mitigating human error and providing an accurate depiction of liver function.The hepatectomy ratio,which is the proportion of the liver volume removed to the total liver volume,is critical in preserving an adequate liver tissue volume to ensure postoperative hepatic functional compensation,minimize surgical complications,and reduce mortality rates.Incorporating the preoperative ALBI score and hepatectomy ratio aids surgeons in assessing the optimal timing and extent of partial hepatectomy.The introduction of preoperative albumin bilirubin score and hepatectomy percentage is beneficial for the surgeons to evaluate the timing and magnitude of partial liver resection.

Interplay of serum biomarkers bilirubin andγ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus

This editorial synthesizes insights from a series of studies examining the interplay between metabolic and oxidative stress biomarkers in cardiovascular disease(CVD),focusing particularly on type-2 diabetes mellitus(T2DM)and acute coronary syndrome(ACS).The central piece of this synthesis is a study that investigates the balance between oxidative stress and antioxidant systems in the body through the analysis of serum bilirubin andγ-glutamyltranspeptidase(γ-GGT)levels in T2DM patients with ACS.This study highlights serum bilirubin as a protective antioxidant factor,while elevatedγ-GGT levels indicate increased oxidative stress and correlate with major adverse cardiovascular events.Complementary to this,other research contributions revealγ-GGT’s role as a risk factor in ACS,its association with cardiovascular mortality in broader populations,and its link to metabolic syndrome,further elucidating the metabolic dysregulation in CVDs.The collective findings from these studies underscore the critical roles ofγ-GGT and serum bilirubin in cardiovascular health,especially in the context of T2DM and ACS.By providing a balanced view of the body’s oxidative and antioxidative mechanisms,these insights suggest potential pathways for targeted interventions and improved prognostic assessments in patients with T2DM and ACS.This synthesis not only corroborates the pivotal role ofγ-GGT in cardiovascular pathology but also introduces the protective potential of antioxidants like bilirubin,illuminating the complex interplay between T2DM and heart disease.These studies collectively underscore the critical roles of serum bilirubin andγ-GGT as biomarkers in cardiovascular health,particularly in T2DM and ACS contexts,offering insights into the body’s oxidative and antioxidative mechanisms.This synthesis of research supports the potential of these biomarkers in guiding therapeutic strategies and improving prognostic assessments for patients with T2DM and some CVD.

Association of total bilirubin with depression risk in adults with diabetes:A cross-sectional study

BACKGROUND Individuals with diabetes mellitus are more likely to experience depression,although most patients remain undiagnosed.The relation between total bilirubin and depression has been increasingly discussed,but limited studies have examined the association of total bilirubin with depression risk in adults with diabetes,which warrants attention.AIM To investigate the association between total bilirubin levels and the risk of depression in adults with diabetes.METHODS The study included adults with diabetes from the National Health and Nutrition Examination Survey 2007-2018.Depression was determined using the Patient Health Questionnaire-9.Multivariable logistic regression,propensity scorematched analysis and restricted cubic spline models were utilized to investigate the association between total bilirubin levels and depression risk in adults with diabetes.RESULTS The study included 4758 adults with diabetes,of whom 602(12.7%)were diagnosed with depression.After adjusting for covariates,we found that diabetic adults with lower total bilirubin levels had a higher risk of depression(OR=1.230,95%CI:1.006-1.503,P=0.043).This association was further confirmed after propensity score matching(OR=1.303,95%CI:1.034-1.641,P=0.025).Subgroup analyses showed no significant dependence of age,body mass index,sex,race or hypertension on this association.Restricted cubic spline models displayed an inverted U-shaped association of total bilirubin levels with depression risk within the lower range of total bilirubin levels.The depression risk heightened with the increasing levels of total bilirubin,reaching the highest risk at 6.81μmol/L and decreasing thereafter.CONCLUSION In adults with diabetes,those with lower levels of total bilirubin were more likely to have depressive symptoms.Serum total bilirubin levels may be used as an additional indicator to assess depression risk in adults with diabetes.

Better performance of PIVKA-II for detecting hepatocellular carcinoma in patients with chronic liver disease with normal total bilirubin

BACKGROUND Serum protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) is a promising biomarker for hepatocellular carcinoma(HCC) surveillance.AIM To identify the contributing factors related to the abnormal elevation of PIVKA-Ⅱ level and assess their potential influence on the performance of PIVKA-Ⅱ in detecting HCC.METHODS This study retrospectively enrolled in 784 chronic liver disease(CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve(AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-Ⅱ for HCC, respectively.RESULTS Elevated PIVKA-Ⅱ levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase(ALP), and total bilirubin(TBIL) for CLD patients and aspartate aminotransferase(AST) and tumor size for HCC patients(all P < 0.05). Serum PIVKA-Ⅱ were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal(ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST(all P < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-Ⅱ was significantly higher compared to that in patients with TBIL > 1 × ULN(0.817 vs 0.669, P = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant(0.783 vs 0.729, P = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.CONCLUSION Serum PIVKA-Ⅱ has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.

Correlation between pre-treatment serum total blood bilirubin andunconjugated bilirubin and prognosis in patients with colorectalcancer

BACKGROUND Epidemiological studies have found that unconjugated bilirubin(UCB)levels are positively correlated with the incidence of colorectal cancer(CRC).Therefore,bilirubin may also play an important role in the prognosis of CRC.AIM To investigate the predictive value of total bilirubin(TBIL)and UCB in the prognosis of patients with CRC.METHODS A total of 142 CRC patients were selected as the research subjects in Jingxian Hospital,from October 2014 to May 2021.General and tumour-related clinical data at admission and the overall survival at 3 years after surgery were collected.The optimal cut-off values of TBIL and UCB were determined by receiver operating characteristic curve analysis.Univariate and multivariate Cox regression were used to analyse the effect of bilirubin level on the survival of CRC patients.The Kaplan–Meier method was used to assess the survival time.RESULTS The 3-year overall survival rate of CRC patients was significantly higher in the high TBIL(>13.45μmol/L)group than in the low TBIL(≤13.45μmol/L)group(76.4%vs 37.1%;P<0.05).The 3-year overall survival rate of CRC patients in the high UCB(>10.75μmol/L)group was significantly higher than that in the low UCB(≤10.75μmol/L)group(83.3%vs 34.2%;P<0.05).Multivariate Cox regression analysis showed that higher TBIL levels were an independent predictor of better prognosis in CRC patients(hazard ratio=0.360,95%confidence interval:0.159-0.812,P=0.014).CONCLUSION TBIL levels can be used as a prognostic indicator for CRC patients.

Predictive value of preoperative albumin-bilirubin score and other risk factors for short-term outcomes after open pancreatoduodenectomy

BACKGROUND Pancreatoduodenectomy represents a complex procedure involving extensive organ resection and multiple alimentary reconstructions.It is still associated with high morbidity,even in high-volume centres.Prediction tools including preoperative patient-related factors to preoperatively identify patients at high risk for postoperative complications could enable tailored perioperative management and improve patient outcomes.AIM To evaluate the clinical significance of preoperative albumin-bilirubin score and other risk factors in relation to short-term postoperative outcomes in patients after open pancreatoduodenectomy.METHODS This retrospective study included all patients who underwent open pancreatic head resection(pylorus-preserving pancreatoduodenectomy or Whipple resection)for various pathologies during a five-year period(2017-2021)in a tertiary care setting at University Medical Centre Ljubljana,Slovenia and Cattinara Hospital,Trieste,Italy.Short-term postoperative outcomes,namely,postoperative complications,postoperative pancreatic fistula,reoperation,and mortality,were evaluated in association with albumin-bilirubin score and other risk factors.Multiple logistic regression models were built to identify risk factors associated with these short-term postoperative outcomes.RESULTS Data from 347 patients were collected.Postoperative complications,major postoperative complications,postoperative pancreatic fistula,reoperation,and mortality were observed in 52.7%,22.2%,23.9%,21.3%,and 5.2%of patients,respectively.There was no statistically significant association between the albumin-bilirubin score and any of these short-term postoperative complications based on univariate analysis.When controlling for other predictor variables in a logistic regression model,soft pancreatic texture was statistically significantly associated with postoperative complications[odds ratio(OR):2.09;95%confidence interval(95%CI):1.19-3.67];male gender(OR:2.12;95%CI:1.15-3.93),soft pancreatic texture(OR:3.06;95%CI:1.56-5.97),and blood loss(OR:1.07;95%CI:1.00-1.14)were statistically significantly associated with major postoperative complications;soft pancreatic texture was statistically significantly associated with the development of postoperative pancreatic fistula(OR:5.11;95%CI:2.38-10.95);male gender(OR:1.97;95%CI:1.01-3.83),soft pancreatic texture(OR:2.95;95%CI:1.42-6.11),blood loss(OR:1.08;95%CI:1.01-1.16),and resection due to duodenal carcinoma(OR:6.58;95%CI:1.20-36.15)were statistically significantly associated with reoperation.CONCLUSION The albumin-bilirubin score failed to predict short-term postoperative outcomes in patients undergoing pancreatoduodenectomy.However,other risk factors seem to influence postoperative outcomes,including male sex,soft pancreatic texture,blood loss,and resection due to duodenal carcinoma.

Measurement of Transcutaneous Bilirubin with Bilicheck as a Jaundice Screening Method in Neonates in Pediatric Emergency Departments

Objectives: To study the reliability of a transcutaneous bilirubinometer (Bilicheck) to determine bilirubin levels in neonates consulting for jaundice in a Paediatric Emergency Department (ED), and to evaluate its usefulness as a screening method. Methods: Prospective observational study realized between June of 2005 and December of2005 inneonates consulting at a paediatric emergency department for jaundice, in whom we realized both transcutaneous and total serum bilirubin measurements (TcB and TSB). We collected demographic variables, analytical variables (serum and transcutaneous bilirubin levels), length of stay in the ED, and need for treatment. Results: 66 children were included aged 2 to 31 days (81% of the sample were 2 to 7 days old). There was a close and statistically significant correlation between TcB and TSB (r = 0.81, p < 0.001). The area under the ROC curve was of 0.90, allowing detecting newborns with jaundice susceptible of treatment with TcB levels ≥ 13 mg/dL (sensitivity 92%, specificity 63, 5%, a positive predictive value 39% and a negative predictive value 97%). The number of venous punctures could be reduced in 50%. The medium stay in the ED was of 2 hours when performing serum measurements. Conclusions: A linear correlation exists between TcB-TSB. TcB measurement cannot replace that of TsB, however it could be used as a screening method in an ED to determine which neonates need confirmation by TsB measurement. The use of transcutaneous bilirubinometer would reduce both the number of painful interventions in neonates and the medium length of stay in ED, consequently reducing iatrogenesis.

Causes of immune dysfunction in hyperbilirubinemia model rats

Objective:To explore the causes of immune dysfunction in neonatal rats with hyperbilirubinemia.Methods:A total of 60 newborn SD rats were equally randomized into normal saline(NS) group,LPS control group,bilirubin control group,low-dose group and high-dose group.After anesthesia,0.1 mL NS was given to the NS and LPS control group and different doses of bilirubin for the other groups;1 h later,the NS and bilirubin control group received the intraperitoneal injection of 0.05 mL NS and 1mg/kg LPS for the other groups.After 5 or 24 hours of model establishment,spleens were collected for detecting the expression levels of MyD88 and p-TAK1 protein and the spleen cells apoptosis by immunohistochemmistry and TUNEL method.After 24 hours of model establishment,scrum inflammatory factors levels and T cell subsets distribution were determined by ELISA and flow cytometry.Results:In contrast to low-dose bilirubin,high-dose bilirubin could induce spleen cells apoptosis in coordination with LPS.After 5 hours of model establishment,compared with NS group.MyD88 expression level in low-dose group elevated while p-TAK1 level in high-dose group reduced(P<0.05).In high-dose group,inflammotory factors levels and CD8^+T cells percentage were all higher than LPS control and NS group(P<0.05),while CD4^+ T cells percentage was lower than NS group(P<0.05).Conclusions:High-concentration plasma bilirubin in coordination with LPS could inhibit NF- κB signal pathways activation and aggravate inflammatory reaction,thus caused immunosuppression with inflammation cascade,which resulted in the immune dysfunction.

Platelet-albumin-bilirubin score - a predictor of outcome of acute variceal bleeding in patients with cirrhosis

BACKGROUND The albumin-bilirubin(ALBI)score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma.Incorporating platelet count in the platelet-albumin-bilirubin(PALBI)score improved validity in predicting outcome of patients undergoing resection and ablation.AIM To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis.METHODS The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed.Child Turcotte Pugh(CTP)class,Model of End-stage Liver Disease(MELD),ALBI and PALBI scores were calculated on admission,and were correlated to the outcome of variceal bleeding.Areas under the receivingoperator characteristic curve(AUROC)were calculated for survival and rebleeding.RESULTS Mean age was 52.6 years;1176 were male(77.5%),69 CTP-A(4.5%),434 CTP-B(29.2%),1014 CTP-C(66.8%);306 PALBI-1(20.2%),285 PALBI-2(18.8%),and 926 PALBI-3(61.1%).Three hundred and thirty-two patients died during hospitalization(21.9%).Bleeding-related mortality occurred in 11%of CTP-B,28%of CTP-C,in 21.8%of PALBI-2 and 34.4%of PALBI-3 patients.The AUROC for predicting survival of acute variceal bleeding was 0.668,0.689,0.803 and 0.871 for CTP,MELD,ALBI and PALBI scores,respectively.For predicting rebleeding the AUROC was 0.681,0.74,0.766 and 0.794 for CTP,MELD,ALBI and PALBI scores,respectively.CONCLUSION PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.

Semi-Quantitative Analysis of Brain MR Imaging in 76 Cases of Neonatal Indirect Hyperbilirubinemia

Background: Neonatal hyperbilirubinemia is indeed common. However, severe nerve injuries and bilirubin encephalopathy are rare and only occur in the unusual cases of extreme hyperbilirubinemia. Objectives: To investigate brain magnetic resonance imaging (MRI) changes and their correlations with perinatal predisposing factors in neonates with indirect hyperbilirubinemia, via regions of interest (ROIs) analysis. Methods: Seventy-six neonates with a gestational age of ≥35 weeks diagnosed with neonatal indirect hyperbilirubinemia or bilirubin encephalopathy all underwent brain MRI during hospitalization. Depending on peak total serum bilirubin (TSB), they were assigned to group A (<221 μmol/L), B (≥221 μmol/L μmol/L), C (≥42 μmol/L μmol/L), or D (≥428 μmol/L). The globus pallidus and the white matter around the anterior horn of the lateral ventricle and posterior horn of the lateral ventricle were selected as the ROIs. Average optical densities (AODs) of the ROIs and the cerebrospinal fluid region were measured. The ratio between the AODs was designated as the relative optical density (ROD), and used to determine relative signal intensity. Results: RODs of the globus pallidus were significantly lower in group D than in all other groups. TSB and the ratio of TSB to serum albumin concentration (B/A) was significantly negatively correlated with ROD in theglobus pallidus. Corrected age was significantly negatively correlated with the ROD of the ROIs. Conclusions: Semi-quantitative image analysis is a feasible method to assess conventional brain MRI for neonatal indirect hyperbilirubinemia. The signal intensity of the globus pallidus in T1-weighted images was significantly correlated with TSB level and B/A.

Correlation between Transcutaneous Bilirubinemia and Blood Bilirubinemia in Screening Term Newborn for Neonatal Jaundice at the Essos Hospital Centre (EHC), Yaoundé, Cameroon

Background: Early and non-invasive diagnosis of neonatal hyperbilirubinemia remains critical in dark skinned babies of low resource settings. Objective: To assess correlation/agreement between transcutaneous bilirubin (Tcb) and serum bilirubin (Tsb) values in full term neonates with jaundice. Methodology: An analytical cross-sectional study was conducted at the neonatology unit of the Essos Hospital Centre (EHC) from January to June 2019. All full-term neonates aged 0 to 7 days with suspected jaundice who did not receive phototherapy were eligible for the study. The enrolled neonates in the study were assessed clinically, then with the MBJ20 transcutaneous bilirubinometer (TcB). The MBJ20 transcutaneous bilirubinometer highest measurement over the forehead and the sternum were compared to TsB. Data were entered and then analysed with the CsPro7.2 and R (version 3.6.0) software. Correlation was captured by Bland & Alman plots and Concordance Correlation Coefficient (CCC) estimates. The Pearson correlation coefficient and Student test for paired data were used for descriptions purposes, and the significance level was 5%. Results: We recruited 88 neonates. The sex ratio of the babies included was 1.25 favouring males. Median Post-natal age was 3 days with 62% aged 72 hours or more. The mean TcB corresponding to the maximum average between frontal and sternal measurement was 153 mg/dl ± 48 and the average Tsb was 123.80 mg/dl ± 50.48. A good linear correlation was found between TcB and total serum bilirubin level r = 0.86 [0.80;0.91]. Positive correlation was noted between both (forehead and sternum) TcB measurements sites, namely r = 0.78 and r = 0.86. The Bland & Altman plot measured the bias at -29.68 mg/l (confidence interval at 95%, 21.14 - 80.50). The CCC estimate was 0.2 varying from -0.22 to 0.76 according to TcB measurement threshold and post-natal age. The ROC area under the curve value for a threshold < 100 mg/l equals 90% proving to be a good predictor for this threshold. Conclusion: A good linear correlation was found despite a poor agreement between TcB and Tsb. TcB method systematically overestimated the value of TsB.

Unconjugated bilirubin alleviates experimental ulcerative colitis by regulating intestinal barrier function and immune inflammation

BACKGROUND Unconjugated bilirubin(UCB) is generally considered toxic but has gained recent prominence for its anti-inflammatory properties. However, the effects of it on the interaction between intestinal flora and organisms and how it influences immune responses remain unresolved.AIM To investigate the role of UCB in intestinal barrier function and immune inflammation in mice with dextran-sulfate-sodium-induced colitis.METHODS Acute colitis was induced by 3%(w/v) dextran sulfate sodium salt in drinking water for 6 d followed by untreated water for 2 d. Concurrently, mice with colitis were administered 0.2 mL UCB(400 μmol/L) by intra-gastric gavage for 7 d.Disease activity index(DAI) was monitored daily. Mice were sacrificed at the end of the experiment. The length of the colon and weight of the spleen were recorded. Serum level of D-lactate, intestinal digestive proteases activity, and changes to the gut flora were analyzed. In addition, colonic specimens were analyzed by histology and for expression of inflammatory markers and proteins.RESULTS Mice treated with UCB had significantly relieved severity of colitis, including lower DAI, longer colon length, and lower spleen weight(colon length: 4.92 ±0.09 cm vs 3.9 ± 0.15 cm; spleen weight: 0.33 ± 0.04 vs 0.74 ± 0.04, P < 0.001). UCB administration inactivated digestive proteases(chymotrypsin: 18.70 ± 0.69 U/g vs44.81 ± 8.60 U/g; trypsin: 1.52 ± 0.23 U/g vs 9.05 ± 1.77 U/g, P < 0.01), increased expression of tight junction(0.99 ± 0.05 vs 0.57 ± 0.03, P < 0.001), decreased serum level of D-lactate(31.76 ± 3.37 μmol/L vs 54.25 ± 1.45 μmol/L, P < 0.001), and lowered histopathological score(4 ± 0.57 vs 7 ± 0.57, P < 0.001) and activity of myeloperoxidase(46.79 ± 2.57 U/g vs 110.32 ± 19.19 U/g, P < 0.001). UCB also regulated the intestinal microbiota, inhibited expression of tumor necrosis factor(TNF) α and interleukin 1β(TNF-α: 52.61 ± 7.81 pg/mg vs 105.04 ± 11.92 pg/mg,interleukin 1β: 13.43 ± 1.68 vs 32.41 ± 4.62 pg/mg, P < 0.001), decreased expression of Toll-like receptor 4(0.61 ± 0.09 vs 1.07 ± 0.03, P < 0.001) and myeloid differentiation primary response gene 88(0.73 ± 0.08 vs 1.01 ± 0.07, P <0.05), and increased expression of TNF-receptor-associated factor 6(0.79 ± 0.02 vs0.43 ± 0.09 P < 0.05) and inhibitor of kappa B α(0.93 ± 0.07 vs 0.72 ± 0.07, P < 0.05)in the colon.CONCLUSION UCB can protect intestinal barrier function, regulate normal intestinal homeostasis, and suppress inflammation via the Toll-like receptor 4/nuclear factor-κB signaling pathway.

Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis(LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded.METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health(Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM(49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012.RESULTS: The baseline serum direct bilirubin concentration was(median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin(2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin wasindependently associated with LNM(OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that:(1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification;(2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and(3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis.CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers.

Adjusting CA19-9 values to predict malignancy in obstructive jaundice:Influence of bilirubin and C-reactive protein

AIM:To find a possible relationship between inflammation and CA19-9 tumor marker by analyzing data from patients with benign jaundice(BJ) and malignant jaundice(MJ).METHODS:All patients admitted for obstructive jaundice,in the period 2005-2009,were prospectively enrolled in the study,obtaining a total of 102 patients.On admission,all patients underwent complete standard blood test examinations including C-reactive protein(CRP),bilirubin,CA19-9.Patients were considered eligible for the study when they presented obstructive jaundice confirmed by instrumental examinations and increased serum bilirubin levels(total bilirubin > 2.0 mg/dL).The standard cut-off level for CA19-9 was 32 U/mL,whereas for CRP this was 1.5 mg/L.The CA19-9 level was adjusted by dividing it by the value of serum bilirubin or by the CRP value.The patients were divided into 2 groups,MJ and BJ,and after the adjustment a comparison between the 2 groups of patients was performed.Sensitivity,specificity and positive predictive values were calculated before and after the adjustment.RESULTS:Of the 102 patients,51 were affected by BJ and 51 by MJ.Pathologic CA19-9 levels were found in 71.7% of the patients.In the group of 51 BJ patients there were 29(56.9%) males and 22(43.1%) females with a median age of 66 years(range 24-96 years),whereas in the MJ group there were 24(47%) males and 27(53%) females,with a mean age of 70 years(range 30-92 years).Pathologic CA19-9 serum level was found in 82.3% of MJ.CRP levels were pathologic in 66.6% of the patients with BJ and in 49% with MJ.Bilirubin and CA19-9 average levels were significantly higher in MJ compared with BJ(P = 0.000 and P = 0.02),while the CRP level was significantly higher in BJ(P = 0.000).Considering a CA19-9 cut-off level of 32 U/mL,82.3% in the MJ group and 54.9% in the BJ group were positive for CA19-9(P = 0.002).A CA19-9 cut-off of 100 U/mL increases the difference between the two groups:35.3% in BJ and 68.6% in MJ(P = 0.0007).Adjusting the CA19-9 value by dividing it by serum bilirubin level meant that 21.5% in the BJ and 49% in the MJ group remained with a positive CA19-9 value(P = 0.003),while adjusting the CA19-9 value by dividing it by serum CRP value meant that 31.4% in the BJ group and 76.5% in the MJ group still had a positive CA19-9 value(P = 0.000004).Sensitivity,specificity,positive predictive values of CA19-9 > 32 U/mL were 82.3%,45% and 59.1%;when the cutoff was CA19-9 > 100 U/mL they were,respectively,68.6%,64.7% and 66%.When the CA19-9 value was adjusted by dividing it by the bilirubin or CRP values,these became 49%,78.4%,69.4% and 76.5%,68.6%,70.9%,respectively.CONCLUSION:The present study proposes CRP as a new and useful correction factor to improve the diag-nostic value of the CA19-9 tumor marker in patients with cholestatic jaundice.

Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy

AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase(UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based chemotherapy.METHODS: The present study was based on a prospective multicenter longitudinal trial of Chinese metastatic colorectal cancer(m CRC) patients treated with irinotecan-based chemotherapy(NCT01282658). Baseline serum bilirubin levels, including total bilirubin(TBil) and unconjugated bilirubin(UBil), were measured,and genotyping of UGT1A1*28 polymorphism was performed. Receiver operating characteristic curve(ROC) analysis was used to determine cutoff values of TBil and UBil. The TBil values were categorized into > 13.0 or ≤ 13.0 groups; the UBil values were categorized into > 4.1 or ≤ 4.1 groups. Combining the cutoff values of TBil and UBil, which was recorded as Co Bil, patients were classified into three groups. The classifier's performance of UGT1A1*28 and Co Bil for predicting treatment response was evaluated by ROC analysis. Associations between response and Co Bil or UGT1A1*28 polymorphism were estimated using simple and multiple logistic regression models. RESULTS: Among the 120 m CRC patients, the serum bilirubin level was significantly different between the UGT1A1*28 wild-type and mutant genotypes. Patients with the mutant genotype had an increased likelihood of a higher TBil(P = 0.018) and a higher UBil(P = 0.014) level compared with the wild-type genotype. Patients were stratified into three groups based on Co Bil. Group 1 was patients with TBil > 13.0 and UBil > 4.1; Group 2 was patients with TBil ≤ 13.0 and UBil > 4.1; and Group 3 was patients with TBil ≤ 13.0 and UBil ≤ 4.1. Patients in Group 3 had more than a 10-fold higher likelihood of having a response in the simple(OR = 11.250; 95%CI: 2.286-55.367; P = 0.003) and multiple(OR = 16.001; 95%CI: 2.802-91.371; P = 0.002) analyses compared with the Group 1 individuals. Patients carrying the UGT1A1*28(TA)7 allele were 4-fold less likely to present with a response compared with the individuals harboring a homozygous(TA)6 genotype in the simple(OR = 0.267; 95%CI: 0.100-0.709; P = 0.008) and multiple(OR = 0.244; 95%CI: 0.088-0.678; P = 0.007) analyses. Classifier's performance of Co Bil and UGT1A1*28 were comparable.CONCLUSION: Co Bil and UGT1A1*28 are both independent biomarkers for predicting the treatment response of m CRC patients to irinotecan-based chemotherapy. After validation, Co Bil, an easily determinable index in the clinic, might be helpful in facilitating stratification of m CRC patients for individualized treatment options.

Post-operative albumin-bilirubin grade predicts long-term outcomes among Child–Pugh grade A patients with hepatocellular carcinoma after curative resection

Background: Although Child–Pugh grade A patients with hepatocellular carcinoma(HCC) are candidates for curative resection, some may have a poor prognosis. The albumin-bilirubin(ALBI) grade, a measure of liver function based on albumin and bilirubin, has the potential to detect Child–Pugh grade A HCC patients with poor prognosis. Because components of the ALBI grade can be measured easily even after surgery, we explored the predictive values of ALBI in patient prognosis after HCC resection. Methods: In this retrospective case-control study, we included 136 HCC patients who underwent curative resection between January 2004 and December 2013 at our hospital. ALBI grade was calculated from laboratory data recorded the day before surgery and at post-operative day 5. Results: Pre-and post-operative ALBI grade predicted patients’ long-term outcomes( P = 0.020 and P < 0.001, respectively, for overall survival, and P = 0.012 and P = 0.015, respectively, for recurrence-free survival). Post-operative ALBI grade was associated with patients’ surgical factors of repeated hepatic resection( P = 0.012), intra-operative bleeding( P = 0.006), and surgery duration( P = 0.033). Furthermore, post-operative ALBI grade, rather than pre-operative ALBI grade, was an independent predictive factor of long-term outcome of Child–Pugh grade A patients with HCC. Conclusions: Post-operative ALBI grade is useful to predict the prognosis in patients after HCC resection.

Assessment of duodenogastric reflux by combined continuous intragastric pH and bilirubin monitoring

AIM: To assess the diagnostic value of a combination of continuous intragastric pH and bilirubin monitoring in the detection of duodenogastric reflux (DGR), and the effects of diet on the bilirubin absorbance. METHODS: 30 healthy volunteers were divided into two groups: standard diet group (Group 1) 18 cases, free diet group (Group 2)12 cases. Each subjects were subjected to simultaneous 24-hour intragastric pH and spectrophotometric bilirubin concentration monitoring (Bilitec 2000). RESULTS: There was no difference of preprandial phase bilirubin absorbance between two groups. The absorbance of postprandial phase was significantly increased in group 2 than group 1. There was no difference between preprandial phase and postprandial phase absorbance in group 1. Postprandial phase absorbance was significantly higher in group 2. In a comparison of bile reflux with intragastric pH during night time, there were 4 types of reflux: Simultaneous increase in absorbance and pH in only 19.6%, increase in bilirubin with unchanged pH 33.3%, pH increase with unchanged absorbance 36.3%, and both unchanged in 10.8%. Linear regression analysis showed no correlation between percentage total time of pH【4 and percentage total time of absorbance】0.14, r=0.068 P【0.05. CONCLUSION: Because of the dietary effect, high absorbance fluids or foods should be avoided in detection. Intragastric pH and bilirubin monitoring separately predict the presence of duodenal (and/or pancreatic) reflux and bile reflux. They can not substitute for each other. The detection of DGR is improved if the two parameters are combined simultaneously.

Bilirubin in coronary artery disease:Cytotoxic or protective?

Bilirubin has traditionally been considered a cytotoxic waste product.However,recent studies have shown bilirubin to have anti-oxidant,anti-inflammatory,vasodilatory,anti-apoptotic and anti-proliferative functions.These properties potentially confer bilirubin a new role of protection especially in coronary artery disease(CAD),which is a low grade inflammatory process exacerbated by oxidative stress.In fact,recent literature reports an inverse relationship between serum concentration of bilirubin and the presence of CAD.In this article,we review the current literature exploring the association between levels of bilirubin and risk of CAD.We conclude that current evidence is inconclusive regarding the protective effect of bilirubin on CAD.A causal relationship between low serum bilirubin level and increased risk of CAD is not currently established.

Effect of preoperative biliary drainage on surgical results after pancreaticoduodenectomy in patients with distal common bile duct cancer:Focused on the rate of decrease in serum bilirubin

AIM: To examine if the rate of decrease in serum bilirubin after preoperative biliary drainagecan be used as a predicting factor for surgical complications and postoperative recovery after pancreaticoduodenectomy in patients with distal common bile duct cancer.METHODS: A retrospective study was performed in 49 consecutive patients who underwent pancrea-ticoduodenectomy for distal common bile duct cancer. Potential risk factors were compared between the complicated and uncomplicated groups. Also, the rates of decrease in serum bilirubin were compared pre- and postoperatively. RESULTS: Preoperative biliary drainage (PBD) was performed in 40 patients (81.6%). Postoperative morbidity and mortality rates were 46.9% (23/49) and 6.1% (3/49), respectively. The presence or absence of PBD was not different between the complicated and uncomplicated groups. In patients with PBD, neither the absolute level nor the rate of decrease in serum bilirubin was significantly different. Patients with rapid decrease preoperatively showed faster decrease during the first postoperative week (5.5 ± 4.4 μmol/L vs -1.7 ± 9.9 μmol/L, P = 0.004).CONCLUSION: PBD does not affect the surgical outcome of pancreaticoduodenectomy in patients with distal common bile duct cancer. There is a certain group of patients with a compromised hepatic excretory function, which is represented by the slow rate of decrease in serum bilirubin after PBD.