Total bilirubin level is associated with acute kidney injury in neonates admitted to the neonatal intensive care units: based on MIMIC-III database.

OBJECTIVE: The objective of this study was to investigate the association between total bilirubin and acute kidney injury (AKI) in neonates admitted to neonatal intensive care units (NICU). METHODS: All data utilized were extracted from Medical Information Mart for Intensive Care-III (MIMIC-III) in this retrospective cohort study. The primary outcome was the occurrence of AKI during hospitalization in the NICU, and the exposure was the initial measurement of total bilirubin levels within 24 h of neonatal admission to the NICU. The relationship between serum total bilirubin and AKI was evaluated by employing univariate and multivariate logistic regression models. Additionally, subgroup analyses were conducted based on birth weight, sepsis, and mechanical ventilation. RESULTS: This retrospective cohort study included a population of 1,726 neonates, and 95 neonates developed AKI. Total bilirubin, as a continuous variable, was linked with decreased AKI risk among neonates admitted to the NICU [odds ratio (OR) = 0.77, 95% confidence interval (CI): 0.64-0.92]. Similarly, when total bilirubin levels were categorized by tertiles, tertiles 3 showed a significant association with decreased AKI risk (OR = 0.39, 95%CI: 0.19-0.83). The relationship of total bilirubin level and AKI was also existent among neonates admitted to the NICU who were underweight, had not sepsis, and received mechanical ventilation. CONCLUSION: Total bilirubin level may be a protective factor for the risk of developing AKI.

Non-linear associations of circulating total bilirubin concentration with the risk of nonalcoholic fatty liver disease and all-cause mortality.

INTRODUCTION AND OBJECTIVES: Accumulating evidence has supported that mild elevated total bilirubin exerts antioxidant and anti-inflammatory properties in multiple metabolic diseases. We aimed to explore the association of circulating total bilirubin concentration with non-alcoholic fatty liver disease (NAFLD) risk and all-cause mortality and examine the potential nonlinear relationships between them. MATERIAL AND METHODS: We used nationally representative data from the National Health and Nutrition Examination Survey (NHANES). NAFLD was assessed using the fatty liver index (FLI) and United States fatty liver index (USFLI), respectively. RESULTS: A total of 35 912 and 17 329 participants were included in FLI-NAFLD (case with NAFLD was diagnosed by FLI) and USFLI-NAFLD (case with NAFLD was diagnosed by USFLI) groups, respectively. The mean age of total population was 46.25 years, and 48.51% were male. Compared to participants with lowest quintile of total bilirubin concentration, those with highest quintile had lower risk of NAFLD in both FLI-NAFLD (OR: 0.48, 95% CI: 0.40, 0.59) and USFLI-NAFLD (OR: 0.55, 95% CI: 0.43, 0.70) groups. Compared to participants with lowest quintile of total bilirubin concentration, the association between total bilirubin concentration and all-cause mortality was not significant among those with highest quintile of total bilirubin concentration (HR: 0.89, 95% CI: 0.66, 1.20). The restricted spline curves showed the nonlinear U-shaped association of total bilirubin concentration with NAFLD risk and all-cause mortality. The segmented linear regression analysis showed negative associations between total bilirubin concentration and risk of NAFLD in both FLI-NAFLD (OR: 0.94, 95% CI: 0.93, 0.95) and USFLI-NAFLD (OR: 0.95, 95% CI: 0.93, 0.96) groups when total bilirubin concentration was below the turning point (FLI-NAFLD: 18.81 µmol/L; USFLI-NAFLD: 15.39 µmol/L) and these associations were not significant when total bilirubin concentration was higher than the turning point. Furthermore, all-cause mortality decreased (OR: 0.97, 95%CI: 0.95, 1.00) with increased total bilirubin concentration up to the turning point (11.97 µmol/L), and then all-cause mortality increased with increasing total bilirubin concentration (OR: 1.03, 95%CI: 1.02, 1.04). CONCLUSIONS: We found that higher circulating total bilirubin concentration within the physiological range was associated with decreased risk of NAFLD and all-cause mortality among NAFLD patients.

Evaluation of a Diazo-Based Point-Of-Care Bilirubin Assay careSTART S1 Total Bilirubin Strip.

BACKGROUND: Neonatal jaundice (NNJ) affects a significant proportion of newborns globally, with an increased burden in low-resource settings. Effective health risk management of NNJ is hindered, particularly in resource-constrained environments, where early detection and treatment are challenging. The careSTART S1 Total Bilirubin Strip, a point-of-care testing (POCT) device based on a diazo-method, offers a potential solution by enabling onsite bilirubin measurement, thus, addressing the gap in early NNJ detection and management. METHODS: The current study evaluated the analytical performance of the careSTART S1 Total Bilirubin Strip for precision, linearity, method comparison, and lot-to-lot consistency following CLSI guidelines. For method comparison, 105 residual EDTA whole blood samples were analyzed with the careSTART S1 Total Bilirubin Strip and compared with reference measurements from the Roche Cobas c702 analyzer. Additionally, statistical analyses, including Passing-Bablok regression and Bland-Altman plots, were performed. RESULTS: The careSTART S1 Total Bilirubin Strip showed allowable (<10%) within-laboratory imprecision of 2.5%-3.6% across all levels and demonstrated linearity over the range of 4.16-439.3 µmol/L. Method comparison revealed a constant negative bias with a mean bias -4.19 µmol/L. However, the 95% confidence interval (-7.10 to -1.28 µmol/L) of the bias is covered by the prespecified allowable bias of 8.3%, at medical decision point. Lot-to-lot variation ranged from 0.14%-6.49%, and was within the acceptable critical difference of 8.3%. CONCLUSION: The careSTART S1 Total Bilirubin Strip provided accurate and reliable bilirubin measurements that could contribute to neonatal care in settings lacking central laboratory facilities.

Hepatic function markers as prognostic factors in patients with acute kidney injury undergoing continuous renal replacement therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), secondary to cardiovascular disease and sepsis, is associated with high in-hospital mortality. Although studies have examined cardiovascular disease and sepsis in AKI, the association between AKI and hepatic functional impairment remains unclear. We hypothesized that hepatic function markers would predict mortality in patients undergoing CRRT. We included 1,899 CRRT patients from a multi-centre database. In Phase 1, participants were classified according to the total bilirubin (T-Bil) levels on the day of, and 3 days after, CRRT initiation: T-Bil < 1.2, 1.2 ≤ T-Bil < 2, and T-Bil ≥ 2 mg/dL. In Phase 2, propensity score matching (PSM) was performed to examine the effect of a T-Bil cutoff of 1.2 mg/dL (supported by the Sequential Organ Failure Assessment score); creating two groups based on a T-Bil cutoff of 1.2 mg/dL 3 days after CRRT initiation. The primary endpoint was total mortality 90 days after CRRT initiation, which was 34.7% (n = 571). In Phase 1, the T-Bil, aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT (De Ritis ratio) levels at CRRT initiation were not associated with the prognosis, while T-Bil, AST, and the De Ritis ratio 3 days after CRRT initiation were independent factors. In Phase 2, T-Bil ≥1.2 mg/dL on day 3 was a significant independent prognostic factor, even after PSM [hazard ratio: 2.41 (95% CI; 1.84-3.17), p < 0.001]. T-Bil ≥1.2 mg/dL 3 days after CRRT initiation predicted 90-day mortality. Changes in hepatic function markers in acute renal failure may enable stratification of high-risk patients.

[Analysis of clinical manifestations and prognosis of primary systemic light chain amyloidosis with liver involvement].

Objective: To summarize the clinical manifestations and prognostic factors of patients with hepatic amyloidosis in a single center. Methods: The clinical data of 28 primary systemic light chain amyloidosis cases with liver involvement in our center from October 2012 to January 2023 were retrospectively analyzed. The main clinical manifestations and prognostic factors were studied. Statistical analysis were performed using the χ(2) test, Fisher's exact test, Wilcoxon rank test, or Kaplan-Meier survival curve log-rank test according to the different data. Results: The main clinical manifestations of patients with liver involvement were abdominal distension, hepatomegaly, and edema. CD56 and chemokine receptor 4 protein expression accounted for 52% (13/25) and 56% (14/25). 64.3% (9/14) patients were combined with t (11,14), and 21.4% (3/14) patients were positive for 1q21 (+), and no patients were detected with del(17p). Univariate analysis showed that Mayo 2004 and 2012 stages and total bilirubin (TBil) ≥34.2 µmol/L were associated with progression-free survival and overall survival. The median progression-free survival and overall survival were significantly inferior in patients with TBil≥34.2µmol/L group (0.178 years, 0.195 years) than with the TBil<34.2µmol/L group (0.750 years, 3.586 years) (P < 0.05). Conclusion: Mayo stage and hyperbilirubinemia are inferior prognostic factors for patients with primary systemic light chain amyloidosis accompanied with liver involvement.

Prior treatment with oxaliplatin-containing regimens and higher total bilirubin levels are risk factors for neutropenia and febrile neutropenia in patients with gastric or esophagogastric junction cancer receiving weekly paclitaxel and ramucirumab therapy: a single center retrospective study.

BACKGROUND: Weekly paclitaxel + ramucirumab (wPTX + RAM) therapy is recommended as the standard second-line chemotherapy regimen for unresectable advanced/recurrent gastric cancer (GC) or esophagogastric junction cancer. Recent subgroup analysis of the RAINBOW trial revealed a higher frequency of severe neutropenia due to wPTX + RAM in Japanese compared to Western patients. However, no risk factors for severe neutropenia have been identified. METHODS: This retrospective observational study included patients with advanced/unresectable gastric or esophagogastric junction cancer who received wPTX + RAM after failure to respond to platinum and fluoropyrimidine doublet chemotherapy between June 2015 and April 2020. We conducted multivariable logistic regression analyses to identify the risk factors associated with grade 4 neutropenia and febrile neutropenia (FN). In addition, we investigated the relationship between the number of risk factors and overall survival (OS) and progression-free survival (PFS). RESULTS: Among 66 patients who met the inclusion criteria, grade 4 neutropenia and FN occurred in 21 (31.8%) and 12 (18.2%) patients, respectively. Prior treatment with oxaliplatin-containing regimens was identified as an independent risk factor for developing grade 4 neutropenia (odds ratio (OR) 20.034, 95% confidence interval (95% CI) 3.216-124.807, P = 0.001). Total bilirubin of > 1.5 mg/dL (OR 31.316, 95% CI 2.052-477.843, P = 0.013) and prior treatment with oxaliplatin-containing regimen (OR 12.502, 95% CI 1.141-137.022, P = 0.039) were identified as independent risk factors for developing FN. Next, we classified patients with 0, 1, 2 risk factor(s) as RF-0, RF-1, and RF-2 subgroups, respectively, and compared the PFS and OS among the three subgroups. PFS was not significantly different among the three subgroups, whereas OS was significantly shorter in the RF-2 subgroup (median 1.4 month, 95% CI 0.0-5.3 month) than in the RF-0 subgroup (median 10.2 month, 95% CI 6.8-13.5 month, P < 0.01 vs RF-2) and RF-1 subgroup (median 13.3 month, 95% CI 10.9-15.7 month, P < 0.01 vs RF-2). CONCLUSIONS: Careful monitoring for grade 4 neutropenia and FN is needed for patients receiving wPTX + RAM therapy who have a history of treatment with oxaliplatin-containing regimens and higher total bilirubin levels.

Cardiohepatic syndrome and its prognostic predictive ability in patients with pulmonary arterial hypertension.

With the development of progressive right ventricular dysfunction, pulmonary arterial hypertension (PAH) is one of the causes of type 2 cardiohepatic syndrome (CHS). Risk assessment, timely and effective management are crucial to improve survival in PAH. Thus, we aimed to evaluate the presence of CHS at diagnosis and its association with prognosis in patients with PAH. One hundred and eighteen consecutive incident patients with PAH between January 2013 and June 2021 were retrospectively included. The presence of CHS was assessed from blood tests taken during diagnostic evaluation and was defined as elevation of at least two of three cholestatic liver parameters; total bilirubin, alkaline phosphatase and gamma-glutamyl transferase. The primary endpoint was all-cause mortality. Patients were followed for a median period of 58 (32-96) months. 23.7% of the patients had CHS at diagnosis. Significantly more patients in CHS (+) group were in intermediate and high-risk categories according to 2015 ESC/ERS guideline, REVEAL 2.0 and REVEAL Lite 2 risk assessment methods (p = .02, .03 and <.001, respectively). The presence of CHS was identified as an independent predictor of mortality (HR: 2.17, 95% CI: 1.03-4.65, p = .03) along with older age (HR: 2.89, 95% CI: 1.50-5.56, p = .001) and higher WHO functional class (HR: 2.57, 95% CI: 1.07-6.22, p = .03). To conclude, presence of CHS at diagnosis in patients with PAH was associated with severe disease and poor prognosis independent of other well known risk factors. As a simple and easy parameter to assess from routinely taken blood tests, CHS should be evaluated in patients with PAH.

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

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

Serum redox markers in uncomplicated type 2 diabetes mellitus accompanied with abnormal iron levels.

OBJECTIVES: This study aimed at evaluating the serum redox status in type 2 diabetes mellitus (T2DM) accompanied with an imbalance in iron concentrations. METHODS: Diabetic patients were grouped according to serum iron levels [normal (DNFe), low (DLFe), and high (DHFe)], and their clinical and redox parameters [total sulfhydryl groups (tSH), uric acid (UA), and total bilirubin (tBILI) as non-enzymatic antioxidants, and malondialdehyde (MDA) and advanced oxidation products of proteins (AOPP) as markers of oxidative stress] were determined. RESULTS: Glucose and HbA1c levels in the T2DM patients did not differ in function of serum iron. T2DM was associated with reduced tSH levels. In the diabetic patients, tSH, UA, and tBILI negatively correlated with MDA, as well as HbA1c with UA. Accordingly, AOPP and MDA were higher in the diabetic groups compared to the controls. The reduced antioxidant capacity was particularly pronounced in the DLFe group, which was further characterized by lower levels of UA and tBILI compared to the other groups. Subsequently, the level of MDA in the DLFe group was higher compared to the DNFe and DHFe groups. The positive correlation between serum iron levels and the antioxidants UA and tBILI, in conjunction with the negative correlation between serum iron levels and the markers of oxidative stress in the diabetic patients, corroborated the indication that comparatively higher level of oxidative stress is present when T2DM coexists with decreased iron levels. CONCLUSIONS: T2DM-associated redox imbalance is characterized by a decrease in serum total sulfhydryl groups and low serum iron-associated reduction in uric acid and total bilirubin levels, accompanied by increased oxidative stress markers. The relatively noninvasive and simple determination of these parameters may be of considerable interest in monitoring the pathophysiological processes in T2DM patients, and may provide useful insights into the effects of potential therapeutic or nutritional interventions.

Association of Different Total Bilirubin Levels with Prognosis of Peritoneal Dialysis-Associated Peritonitis.

Background and Objectives: Peritoneal dialysis-associated peritonitis (PDAP) poses significant challenges in peritoneal dialysis (PD) patient management and outcomes. Total bilirubin has gained attention due to its antioxidant and immunomodulatory properties. However, its relationship with PDAP prognosis remains underexplored. Materials and Methods: We conducted a retrospective single-center study involving 243 PDAP patients stratified into tertile-based groups according to total bilirubin levels. The association between total bilirubin levels and treatment failure risk was investigated through statistical analyses and restricted cubic spline curve analysis. Results: Our analysis revealed a non-linear correlation between total bilirubin levels and PDAP treatment failure risk. At total bilirubin levels below 8.24 µmol/L, a protective effect was observed, while levels exceeding this threshold heightened the risk of treatment failure. Conclusions: This study unveils a dual role of total bilirubin in PDAP prognosis. Below a certain threshold, it confers protection, while higher levels exacerbate the risk of treatment failure. These findings emphasize the need for further investigation in larger, multicenter prospective studies to validate and elucidate the mechanisms behind bilirubin's impact on PDAP, potentially guiding the development of targeted therapeutic strategies.

High total bilirubin-to-uric acid ratio predicts poor sleep quality after acute ischemic stroke: a prospective nested case-control study.

BACKGROUND: Sleep disorders are prevalent after stroke, resulting in high recurrence rates and mortality. But the biomarkers of sleep disorders in stroke patients remain to be elucidated. This study aimed to explore the relationship between total bilirubin-to-uric acid ratio (TUR) and sleep quality after acute ischemic stroke (AIS). METHODS: Three hundred twenty-six AIS patients were recruited and followed up 1 month after stroke in our study. Serum total bilirubin and uric acid levels were obtained within 24 h after admission. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality 1 month after stroke. We conducted receiver operating characteristic (ROC) curve analysis and screened the optimal biomarker to differentiate sleep disorders after stroke. Then the TUR was stratified according to the best cut-off value (0.036) of the ROC and further analysed by binary logistic regression analysis. Additionally, the interaction was used to explore the difference in its effect on post-stroke sleep quality in different subgroups. RESULTS: Three hundred thirty-one patients (40.2%) were considered as having poor sleep quality during the one-month follow-up. Compared to patients with good sleep, patients with poor sleep were more likely to have higher TUR (IQR), 0.05 (0.03-0.06) versus 0.03 (0.02-0.04), P < 0.001. After adjusting for confounding factors, binary regression analysis demonstrated that a high TUR (≥0.036) was independently related to post-stroke poor sleep quality (OR = 3.75, 95% CI = 2.02-6.96, P < 0.001). CONCLUSIONS: High TUR is associated with an increased risk of poor sleep quality in AIS patients, especially in females, diabetics, and patients with hyperlipidaemia.

Evaluation of the performance of simple laboratory parameters used in the diagnosis of acute appendicitis.

Background: Acute appendicitis (AA) is one of the most common emergency surgery. Aim: To evaluate the performance of laboratory parameters used in the diagnosis of AA. Subjects and Methods: There were two groups. In both groups, leukocyte (WBC), neutrophil, lymphocyte count, neutrophil/lymphocyte ratio (NLR), mean platelet volume (MPV), red cell distribution width (RDW), and platelet distribution width (PDW) values were examined in complete blood count (CBC). In addition, serum bilirubin (total bilirubin and direct bilirubin) values were examined. All laboratory parameters studied were compared to evaluate their diagnostic performance. Results: A total of 128 people were in the AA group and 122 people were in the healthy group (control). WBC count, neutrophil count, NLR, total bilirubin, direct bilirubin, and PDW values were significantly higher in the AA group than in the control group (P value <0.05). Lymphocyte counts and MPV values in the AA group were significantly lower than in the control group (P value <0.05). The sensitivity and selectivity of the WBC and neutrophil counts in AA were 95.13%, 89.34%, 94.53%, and 93.44%, respectively. The sensitivity and selectivity of the total bilirubin values were 59.38% and 73.77%, respectively. Area under the ROC curve (AUC) values within 95% confidence interval were over 0.900 for neutrophil count, WBC count, direct bilirubin, NLR, and PDW values. AUC values for total bilirubin, lymphocyte count, RDW, and MPV values were below 0.700. Conclusions: Diagnostic performances of the laboratory parameters were determined as follows: neutrophil count > WBC count > direct bilirubin = NLR = PDW > total bilirubin = lymphocyte count = RDW = MPV.

Antioxidant and inflammatory biomarkers in herpes zoster.

The risk of herpes zoster (HZ) increases as cell-mediated immunity declines with age. Even though oxidative stress plays a crucial role in the development of HZ, there are few serum biomarkers of the disease's antioxidant activity. The purpose of this study is to investigate the blood levels of major antioxidants in HZ patients. To the best of our knowledge, this is the first study on this issue in the literature. The serum levels of antioxidants including uric acid (UA), total bilirubin (TBIL), albumin (ALB), vitamin D levels, and inflammatory markers such as homocysteine (Hcy) and C-reactive protein (CRP) was retrospectively analyzed in 53 patients with HZ and 53 age-and sex-matched healthy controls (HCs). The relationships between these markers and postherpetic neuralgia (PHN) and the clinical severity of HZ were also evaluated. Serum levels of UA, TBIL, and ALB in patients with HZ were significantly lower than those in the HCs (p < 0.001), while no statistical differences were found in vitamin D levels between the groups. Hcy and CRP levels were significantly increased in HZ patients compared to HCs. Significant differences were observed in the serum levels of UA, Hcy, CRP, and vitamin D in the PHN group versus the non-PHN group (p < 0.001). The presence of inflammatory markers was found to be positively related to disease activity. Furthermore, when compared to the mild or moderate clinical types of HZ, these biomarkers were statistically significant in the severe clinical type. These results suggest that uncontrolled varicella-zoster virus reactivation, acute nerve damage, and PHN may all be associated with low antioxidant levels. These biomarkers may be a protective factor for HZ, but more research is needed to clarify the underlying mechanism.

Alterations in gut microbiota and elevated serum bilirubin in primary biliary cholangitis patients treated with ursodeoxycholic acid.

BACKGROUND: The prognosis of primary bile cholangitis (PBC) is linked to gut microbiota dysbiosis. This study investigated the association between the gut microbiome and elevated total bilirubin (TB) level in PBC patients treated with ursodeoxycholic acid (UCDA). METHODS: A total of 47 PBC patients with 12 months of UCDA treatment were enrolled. Patients were divided into the TB (+) (TB>1× upper limit of the normal range [ULN]; n = 20) and TB(-) (TB≤1× ULN; n = 27) groups. Stool and serum specimens were collected, and microbiota composition and functional characteristics in the 2 groups were evaluated by 16S RNA gene sequencing and bioinformatic analysis. RESULTS: Bacterial diversity was lower in the TB(+) group than in the TB(-) group, although there was no significant difference in bacterial community profile. The phylum Saccharibacteria showed differential abundance in the 2 groups. Meanwhile, the TB(-) group had lower abundance of the Gemmiger, Blautia, Anaerostipes and Coprococcus genera than the TB(+) group, whereas Holdemania was absent. The abundance of Gemmiger formicillis and Coprococcus eutactus was positively correlated with that of Faecalibacterium prausnitzii, while Blautia, Anaerostipes and Coprococcus were negatively correlated with total bile acid level. CONCLUSION: TB level in PBC patients treated for 12 months with UCDA is associated with a distinct gut microbiome profile.

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid.

BACKGROUND & AIMS: Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. METHODS: Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). RESULTS: One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin≥1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. CONCLUSIONS: An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level ≥1.4 mg/dl should discourage from its use.

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

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

Serum total bilirubin and long-term prognosis of patients with new-onset non-ST elevation myocardial infarction: a cohort study.

BACKGROUND: The potential prognostic role of total bilirubin (TBIL) in patients with new-onset non-ST elevation myocardial infarction (NSTEMI) is not fully understood. This study aims to evaluate the potential predictive value of TBIL for long-term prognosis in patients with new-onset NSTEMI. METHODS: Patients with new-onset NSTEMI that underwent emergency coronary angiography in our department from June 2015 to March 2020 were included. Baseline TBIL was measured at admission. SYNTAX scores were used to indicate the severity of coronary lesions. The association between TBIL and SYNTAX scores was analyzed using multivariate logistic regression. The patients were followed for the incidence of major adverse cardiac and cerebrovascular events (MACCEs). The association between TBIL and MACCEs was analyzed using Kaplan-Meier survival methods. RESULTS: In total 327 patients were included in this study. Patients were divided according to tertiles of TBIL (first tertile < 10.23 µmol/L, n = 109; second tertile 10.23-14.30 µmol/L, n = 109; and third tertile ≥ 14.30 µmol/L, n = 109). TBIL was independently associated with the severity of coronary lesions in patients with NSTEMI, with an adjusted odds ratio (OR) and 95% confidence interval (CI) for the third tertile and the second tertile compared with the first tertile of TBIL of 2.259 (1.197-4.263) and 2.167 (1.157-4.059), respectively (both p < 0.05). After a mean follow-up of 30.33 months, MACCE had occurred in 57 patients. TBIL was independently associated with the increased risk of MACCEs, with an adjusted hazard ratio (HR) and 95% CI for the third tertile and the second tertile compared with the first tertile of TBIL of 2.737 (1.161-6.450) and 3.272 (1.408-7.607), respectively (both p < 0.05). CONCLUSIONS: Higher myocardial infarction admission TBIL might independently predict poor prognosis in patients with NSTEMI.

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

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

Association between Initial Serum Total Bilirubin and Clinical Outcome in Myocardial Infarction with Non-Obstructive Coronary Arteries.

Background: Liver function parameters, particularly serum total bilirubin (TB), are closely associated with cardiovascular diseases. However, the impact of serum TB among patients with myocardial infarction and non-obstructive coronary (MINOCA) remains unknown. Our study investigated the relationship between serum TB at admission and long-term adverse clinical outcomes in MINOCA patients. Methods: A total of 273 consecutive MINOCA patients were categorized into low and high serum TB groups based on the optimal cut-off of 0.9 mg/dl. The primary endpoint was major adverse cardiovascular events (MACE), including cardiac death, non-fatal MI, heart failure, and angina rehospitalization. Receiver-operating characteristic, Cox regression, and Kaplan-Meier analyses were used to evaluate the association of high serum TB with cardiovascular outcomes. Results: High serum TB was found in 68 (24.9%) patients. The incidence of MACE was higher in the high TB group than in the low TB group after a median follow-up of 28 months (30.9 vs. 17.1%, P=0.015). The Kaplan-Meier curve analysis also indicated that patients in the high TB group had a higher risk of developing MACE (log-rank P=0.023). Cox regression analysis showed that high serum TB (>0.9mg/dl) significantly correlated with increased MACE risk (HR=1.90, 95%CI: 1.12-3.22, P=0.018). After adjusting for numerous clinical variables, the high serum TB remained significantly associated with an increased risk of MACE (HR=2.04, 95%CI: 1.05-3.94, P=0.034). Conclusion: High initial serum TB (>0.9mg/dl) is a robust predictor of poor clinical outcomes among MINOCA patients. In clinical settings, assessing serum TB at admission may help identify high-risk patients presenting with MINOCA.

Association between total bilirubin and bone mineral density level in adolescents.

BACKGROUND: Increasing bone mass accumulation in adolescence and obtaining greater peak bone mass is one of the effective methods to prevent osteoporosis in the future. We aimed to examine the association between total bilirubin and bone mineral density (BMD) level in adolescents. METHODS: We used the data from 2005-2010 and 2013-2014 cycles of National Health and Nutrition Examination Survey (NHANES). The BMD levels in the region of lumbar spine and femoral regions, including total femur, femoral neck, trochanter, and intertrochanter were measured. Univariable and multivariable linear regression model were used to assess the relationship between total bilirubin concentration and BMD. RESULTS: A total of 3741 participants aged 12-19 years were ultimately included in the study. There were 1997 (53.38%) males and 1744 (46.62%) females. Univariate analysis results showed that age, sex, race, education, income, body mass index, dietary calcium intake, and diabetes were correlated with BMD levels. Compared with the lowest quartile of total bilirubin concentration, the highest quartile of total bilirubin concentration was positively associated with BMD levels in the regions of total femur (ß = 0.036, 95% CI = 0.021 to 0.050, P < 0.001), femur neck (ß = 0.030, 95% CI = 0.016 to 0.044, P < 0.001), trochanter (ß = 0.033, 95% CI = 0.019 to 0.046, P < 0.001), intertrochanter (ß = 0.040, 95% CI = 0.023 to 0.056, P < 0.001), and lumbar spine (ß = 0.032, 95% CI = 0.018 to 0.045, P < 0.001). We also observe the same trend in sensitivity analysis (P for trend < 0.001). CONCLUSION: Our study demonstrated that total bilirubin concentration was positively associated with BMD levels in adolescents in United States. Total bilirubin concentration might be a protective marker against bone loss in adolescents.