Lower Total Bilirubin Levels Research Articles

Effects of perioperative steroid use on surgical stress and prognosis in patients undergoing hepatectomy: a systematic review and meta-analysis of randomized controlled trials.

The objective of this study was to evaluate the clinical effects of perioperative steroid hormone usage in hepatectomy patients through a comprehensive systematic review and meta-analysis. Prospective randomized controlled trials (RCTs) investigating the perioperative use of steroid hormones in hepatectomy patients were systematically searched using various databases, including PubMed, Medline, Embase, the Cochrane Library, the Chinese Biomedical Literature Database, Wanfang Data, and the CNKI database. Two researchers independently screened and extracted data from selected studies. Data analysis was performed using RevMan 5.3 software. The results revealed significantly lower levels of total bilirubin (standard mean difference [SMD] = -0.7; 95% CI: -1.23 to -0.18; and p = 0.009), interleukin-6 (SMD = -1.02; 95% CI: -1.27 to -0.77; and p < 0.001), and C-reactive protein (SMD = -0 .65; 95% CI: -1 .18 to -0.11; and p = 0.02) on postoperative day 1 (POD 1), as well as a reduced incidence of postoperative complications in the steroid group compared to the placebo group. No significant differences were observed between the two groups regarding alanine aminotransferase (ALT) levels, aspartic aminotransferase (AST) levels, or specific complications such as intra-abdominal infection (p = 0.72), wound infection (p = 0.1), pleural effusion (p = 0.43), bile leakage (p = 0.66), and liver failure (p = 0.16). The meta-analysis results indicate that perioperative steroid usage can effectively alleviate liver function impairment and inflammation response following hepatectomy while improving patient prognosis.

The Evaluation of the Genetic Variation Types of the Uridine Diphosphate Glucuronosyl Transferase 1A1 Gene by Next-Generation Sequencing and Their Effects on Bilirubin Levels in Obese Children.

Background and Objectives: Obesity is a major nutritional problem with an increasing prevalence among children and adolescents. The uridine-diphosphate-glucuronosyl-transferase1A1 (UGT1A1) gene encodes the UDP-glucuronosyl transferase enzyme, converting the toxic form of bilirubin to a soluble, nontoxic form. There are yet to be studies on the evaluation of the UGT1A1 variant types detected by next-generation sequencing (NGS) and their effects on bilirubin levels in nonsyndromic obese children. Methods: Forty-five children with body mass index (BMI) >95 percentile (p) constituted the obesity group and fourteen healthy children with BMI <85p constituted the control group. Anthropometric, clinical features, and biochemical parameters were evaluated. Furthermore, the UGT1A1 gene was sequenced by NGS. Results: The obese patients had lower total, direct, and indirect bilirubin levels (p = 0.422, 0.026, and 0.568, respectively). In addition, obese patients had more genetic variations in the UGT1A1 gene compared with the control group (62.2% and 50%, respectively). We found that children with variations had higher total direct and indirect bilirubin levels compared with those without variation (p = 0.016, 0.028, and 0.015, respectively). Children diagnosed with obesity in the first two years of their life had fewer genetic variations and lower total bilirubin levels (p = 0.000 and 0.013, respectively). Conclusions: It is assumed that bilirubin can be protective against many chronic diseases. Although bilirubin levels are found to be lower in obese children compared with the control group, some variations in the UGT1A1 gene may be supported by raising bilirubin. We suggest that high bilirubin levels caused by those UGT1A1 variations may be protective against obesity and its many negative effects.

ASSOCIATION BETWEEN TOTAL BILIRUBIN LEVELS WITH INCIDENCE OF ATHEROSCLEROSIS: SYSTEMATIC REVIEW AND META-ANALYSIS

Background. Bilirubin is a byproduct of the breakdown of erythrocytes. Bilirubin levels can potentially serve as a biomarker for cardiovascular risk assessment. In this study, we would be investigating most recent manuscripts, published in the last 5 years, that studied association of serum bilirubin level to atherosclerosis progression to elicit how strongly low level of total bilirubin can prognose the disease progression. Methods. Using Pubmed search engine, all articles that included keywords “bilirubin” and “atherosclerosis” were retrieved. In total 67 search results emerged for the 2019-2023 timeline, the last 5 years.6 population-based studies that studied association between total bilirubin concentration and atherosclerosis development were used for the meta-analysis. Results. Increasing blood total bilirubin level seems to decrease the odds of developing atherosclerosis, meaning that there is an inverse correlation between total bilirubin level and arterial plaque formation or stenosis. Pooled odds ratio was found to be 0.86 (95% CI 0.83-0.9), suggesting that there is 14% decreased chance of developing atherosclerosis for each mmol/L increase in bilirubin levels. Overall, higher total serum bilirubin levels were associated with a significantly decreased risk of progression to atherosclerosis. Conclusion. The meta-analysis indicates a significant inverse association between low total bilirubin levels and the risk of developing atherosclerosis, suggesting that higher bilirubin levels may be protective against the progression of this disease.

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 score-matched 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 6.81 μmol/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.

Prediction of prognosis in patients with ischemic stroke combined with type 2 diabetes mellitus based on serum total bilirubin levels.

Serum bilirubin levels may have therapeutic benefits in oxidative stress-related diseases, but their role in stroke remains unclear. This study aimed to investigate the relationship between serum bilirubin levels on admission and clinical outcomes in ischemic stroke patients. We prospectively collected data from consecutive ischemic stroke admissions. Serum total bilirubin (TBIL) and direct bilirubin levels on admission were measured. Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale, and functional status at discharge was evaluated using the modified Rankin scale. Among 180 patients, lower TBIL levels were observed in all 3 groups, with the mild group (7.89 ± 2.12 μmol/L) having lower levels than the moderate group (8.01 ± 2.12 μmol/L) and the severe group (9.12 ± 2.12 μmol/L). Although TBIL levels were initially associated with stroke severity, this relationship did not hold after adjusting for confounding factors. Serum bilirubin levels appear to be related to stroke severity but not independently associated with outcomes in ischemic stroke patients. Further research is needed to understand the underlying mechanisms of this relationship. There is a strong correlation between serum bilirubin levels and the severity and prognosis of ischemic stroke in patients with type 2 diabetes. Therefore, early control of serum TBIL and direct bilirubin is crucial for the treatment and prognosis of ischemic stroke in patients with type 2 diabetes.

The causal effect of oxidative stress on the risk of glaucoma

Glaucoma is a complex multifactorial disease. Oxidative stress has been implicated in its pathogenesis. However, establishing a causal relationship between oxidative stress and glaucoma is challenging due to confounding and reverse causality. In this study, we performed bidirectional two-sample Mendelian randomization (MR) analyses based on genetic instrumental variables as proxies for 11 biomarkers of oxidative stress injury to investigate the causal relationship between oxidative stress and glaucoma. Eight significant associations were identified. Increased circulating levels of catalase (OR = 0.915, 95 % CI: 0.848–0.987, P = 0.022), retinol (OR = 0.481, 95 % CI: 0.248–0.932, P = 0.044) and superoxide dismutase (OR = 0.779, 95 % CI: 0. 616-0.986, P = 0.038) are associated with a decreased risk of glaucoma, whereas an increased myeloperoxidase level (OR = 2.145, 95 % CI: 1.119–4.111, P = 0.029) is associated with an increased risk of glaucoma. Glaucoma was causally associated with lower levels of total bilirubin (OR = 0.961, 95 % CI: 0.927–0.997, P = 0.039), glutathione peroxidase (OR = 0. 934, 95 % CI: 0.890–0.981, P = 0.006), paraoxonase (OR = 0.883, 95 % CI: 0.810–0.963, P = 0.005) and albumin (OR = 0.988, 95 % CI: 0.978–0.998, P = 0.014). The bidirectional MR analysis revealed a causal relationship between oxidative stress and glaucoma. These findings provide a greater understanding of the underlying mechanisms of glaucomatous neurodegeneration and imply a potential therapeutic approach for glaucoma through targeting oxidative stress pathways.

Hemoadsorption Therapy for Critically Ill Patients with Acute Liver Dysfunction: A Meta-Analysis and Systematic Review.

Critically ill patients are at risk of developing acute liver dysfunction as part of multiorgan failure sequelae. Clearing the blood from toxic liver-related metabolites and cytokines could prevent further organ damage. Despite the increasing use of hemoadsorption for this purpose, evidence of its efficacy is lacking. Therefore, we conducted this systematic review and meta-analysis to assess the evidence on clinical outcomes following hemoadsorption therapy. A systematic search conducted in six electronic databases (PROSPERO registration: CRD42022286213) yielded 30 eligible publications between 2011 and 2023, reporting the use of hemoadsorption for a total of 335 patients presenting with liver dysfunction related to acute critical illness. Of those, 26 are case presentations (n = 84), 3 are observational studies (n = 142), and 1 is a registry analysis (n = 109). Analysis of data from individual cases showed a significant reduction in levels of aspartate transaminase (p = 0.03) and vasopressor need (p = 0.03) and a tendency to lower levels of total bilirubin, alanine transaminase, C-reactive protein, and creatinine. Pooled data showed a significant reduction in total bilirubin (mean difference of -4.79 mg/dL (95% CI: -6.25; -3.33), p = 0.002). The use of hemoadsorption for critically ill patients with acute liver dysfunction or failure seems to be safe and yields a trend towards improved liver function after therapy, but more high-quality evidence is crucially needed.

Biomarkers for Risk Stratification in Patients With Type A Acute Aortic Dissection

Type A acute aortic dissection (AAD) is a fatal disease and thus, accurate and objective risk stratification is essential. In the present study, we evaluated a prognostic value of readily available and assessable biomarkers in patients with type A AAD. This was a retrospective, multicenter, observational study. A total of 703 patients with type A AAD diagnosed by contrast-enhanced computed tomography were included. Therapeutic strategies were left to the physician's discretion in a real-world clinical setting. The prognostic value for in-hospital mortality was examined in 15 circulating biomarkers on admission which are routinely available in clinical practice. Of the 703 patients, 126 (17.9%) died during the hospitalization. Among the 15 biomarkers, the multivariable analysis identified positive cardiac troponin, a low total bilirubin (T-Bil) level, and elevated levels of brain natriuretic peptide (BNP) and lactate dehydrogenase (LDH) as significant predictors of in-hospital death. Receiver operating characteristics curve analysis showed that these 4 biomarkers had an independent additive prognostic value. With the cut-off values of T-Bil, BNP, and LDH in combination with positive troponin, the increase in the number of positive biomarkers was progressively associated with higher in-hospital mortality from 1.3% to 9.8%, 20.5%, 36.4%, and 75.0% (p<0.001). In conclusion, among patients with type A AAD, positive cardiac troponin, a low T-Bil level, and elevated levels of BNP and LDH on admission were related to higher in-hospital mortality with an incremental prognostic value, suggesting that the readily available and assessable biomarkers can aid in decision-making in therapeutic strategies.

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis.

Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

Predictors of Post-ERCP Pancreatitis (P.E.P.) in Choledochal Lithiasis Extraction.

In the present era, post-ERCP pancreatitis (PEP) stands out as one of the most commonly occurring complications associated with endoscopic choledochal lithiasis extraction. The ability to predict the occurrence of such an event, particularly by utilizing absolute values and ratio dynamics of the emergency blood tests, constitutes the primary step in effectively managing a patient with a complex pathology. The study involved 134 patients who performed ERCP to extract choledochal lithiasis (n = 48 with PEP and n = 86 without PEP). The results revealed increased risks of post-ERCP pancreatitis in women and lower risks in those who benefited from manipulation of the main bile duct with the Dormia probe and dilatation balloon (OR: 2.893 CI 95%: 1.371-6.105, p = 0.005 and respectively OR: 0.346 CI 95%: 0.156-0.765, p = 0.009), without biliary stent placement. Moreover, the results brought novel elements to the literature, showing that higher values of CRPR (OR: 4.337 CI 95%: 1.945-9.668; p < 0.001), TBIR (4.004 CI 95%: 1.664-9.634; p = 0.002) and NLR post-ERCP (3.281 CI 95%: 1.490-7.221; p = 0.003) are predictive for PEP. Nevertheless, lower total bilirubin levels upon admission are predictive of PEP with an OR of 5.262 (95% confidence interval: 2.111-13.113, p < 0.001).

Natural History of Optic Disc With Physiologic Large Cup: Incidence, Predictors of Glaucoma Conversion After Minimum 10-Year Follow-up

To investigate the natural history of optic disc with physiologic large cup (PLC) (ie, vertical cup/disc ratio [VCDR] ≥0.6 without retinal nerve fiber layer defect) and the risk factors for glaucoma conversion. Observational retrospective cohort study. Subjects who underwent a health screening examination at Seoul National University Hospital Healthcare System Gangnam Center from 2003 to 2010 (n=76,030) were involved. The prevalence of PLC in the cohort was analyzed. The incidence rate of glaucoma conversion was estimated per 100 person-years among cases with a follow-up period longer than 10 years. Multivariate Cox proportional hazards regression was used to identify ocular and systemic factors associated with glaucoma conversion. Among 74,617 eligible subjects, 3569 subjects (4.8%) had PLC. Of those with a follow-up period longer than 10 years (n=859), the incidence rate of glaucoma conversion was 0.95 per 100 person-years. A total of 12.1% of PLC eyes progressed to glaucoma after 8.7 ± 3.9 years (range, 2.0-16.5 years). Higher VCDR (adjusted hazard ratio [aHR]=4.36; 95% CI=2.675-7.103), violation of the inferior superior nasal temporal neuroretinal rim thickness rule (aHR=1.86; 95% CI=1.057-3.258), presence of retinal arterial sclerosis (aHR=1.63; 95% CI=1.040-2.550), and lower total bilirubin level (aHR=0.58; 95% CI=0.340-0.991) were associated with glaucoma development. This study identified the prevalence of PLC as well as the incidence rate of glaucoma conversion and the risk factors for glaucoma development in PLC eyes. The natural history of PLC may help clinicians to better understand its risk factors and the specific management needs of their patients.

Synthesis and In vivo Evaluation of Hepatoprotective Effects of Novel Sulfur-Containing 1,4-Dihydropyridines and 1,2,3,4-Tetrahydropyridines

Background: Hepatoprotectors, currently used in clinical practice, often show low efficacy. One of the promising goals in the therapy of liver diseases is the targeted synthesis of smallmolecule drugs with hepatoprotective activity. Some heterocycles, such as 1,4-dihydropyridines, are proven to be good hepatoprotectors. Objective: This study aimed to prepare and investigate the hepatoprotective effects of some dihydro- and tetrahydro pyridines using the experimental rat model of tetrachloromethane (CCl4)- induced acute liver damage. Methods: Several 1,4-dihydropyridines and 1,2,3,4-tetrahydropyridines were synthesized by the reaction of cyanothioacetamide with carbonyl compounds and active methylene compounds, such as Meldrum’s acid, ethyl cyanoacetate or β-keto esters, followed by S-alkylation of intermediate pyridine-2-thiolates. In silico prediction studies were performed to explore the possible protein targets. Using virtual bioscreening tools, we selected the six most promising compounds from the library of new partially saturated pyridines. Six novel compounds were characterized by IR, 1H, 13C DEPTQ NMR spectroscopy, 2D NMR experiments (1H–13C HSQC, 1H–13C HMBC), HRMS (ESI), and elemental analysis. The hepatoprotective effects were studied in vivo on eighty white rats with CCl4-induced liver damage. Biochemical studies, including thymol turbidity test and measurements of levels of bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase in the blood of rats, were performed. Results: Five of six studied compounds showed a good hepatoprotective effect on a rat model of tetrachloromethane (CCl4)-induced acute hepatitis. The blood of rats in the experimental groups revealed significantly lower levels of total bilirubin, alanine aminotransferases, aspartate aminotransferases, thymol turbidity and alkaline phosphatase compared to the control group of rats with acute toxic tetrachloromethane hepatitis. Conclusion: Our results suggests that compound, (benzyl 4-(4-chlorophenyl)-5-cyano-6-({2-[(3,4- dimethylphenyl)amino]-2-oxoethyl}thio)-2-methyl-1,4-dihydropyridine-3-carboxylate), can be considered as candidate for further preclinical studies. Moreover, as per our knowledge, this is the first report on the hepatoprotective effects of the 1,2,3,4-tetrahydropyridine series.

Blood unconjugated bilirubin and tacrolimus are negative predictors of specific cellular immunity in kidney transplant recipients after SAR-CoV-2 inactivated vaccination

The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Here, observational study demonstrated no severe adverse effects were observed in KTRs and healthy participants (HPs) after first or second dose of SARS-CoV-2 inactivated vaccine. Different from HPs with excellent immunity against SARS-CoV-2, IgG antibodies against S1 subunit of spike protein, receptor-binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after the second dose of inactivated vaccine. Specific T cell immunity response was detectable in 40% KTRs after the second dose of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentrations. Multivariate logistic regression analysis found that blood unconjugated bilirubin and tacrolimus concentration were significantly negatively associated with SARS-CoV-2 specific T cell immunity response in KTRs. Altogether, these data suggest compared to humoral immunity, SARS-CoV-2 specific T cell immunity response are more likely to be induced in KTRs after administration of inactivated vaccine. Reduction of unconjugated bilirubin and tacrolimus concentration might benefit specific cellular immunity response in KTRs following vaccination.

Daily Vitamin D Supplementation Improves Vitamin D Deficiency in Patients With Chronic Liver Disease.

The objective of this article is to evaluate the response to 6000 IU oral cholecalciferol (OC) treatment in children with chronic liver disease (CLD) and 25(OH)D deficiency. This historical cohort included non-transplanted CLD patients younger than 18 years old, which were analyzed for serum 25(OH)D, liver function, bone metabolism, Child-Pugh classification, and anthropometry. Patients with 25(OH)D deficiency (defined as 25(OH)D < 20 ng/mL) who received 6000 IU/day of OC were analyzed pre- and post-intervention, and considered responders if 25(OH)D > 20 ng/mL after at least 60 days. We compared clinical and laboratory data from patients with and without 25(OH)D deficiency, responders and nonresponders. We studied 96 patients, of which 57.2% had biliary atresia. The prevalence of 25(OH)D deficiency was 67.7% (65/96). These patients were younger ( P < 0.001), had higher Child-Pugh scores ( P < 0.001), higher levels of total bilirubin (TB) ( P < 0.001), gamma-glutamyl transferase ( P < 0.001), and alkaline phosphatase ( P = 0.002), as well as lower levels of phosphorus ( P = 0.009) compared with patients without 25(OH)D deficiency. The median treatment length was 126 days (70-307 days). At the end of treatment, we observed a higher median of 25(OH)D ( P < 0.001), and lower median of parathyroid hormone (PTH) ( P = 0.023). Nine patients (29%) restored 25(OH)D to normal range; they had lower Child-Pugh score ( P = 0.001), lower TB levels ( P = 0.001), and higher level of phosphorus ( P = 0.003) after treatment. Despite an increase in 25(OH)D and decrease in PTH levels, 6000 IU/day of OC was not sufficient to restore 25(OH)D deficiency in most of the patients in this study.

Association between bilirubin levels with incidence and prognosis of stroke: A meta-analysis.

Bilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted. Studies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17. A total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference = -1.33 μmol/L, 95% CI: -2.12 to -0.53, P < 0.001). Compared with the lowest bilirubin level, total odds ratio (OR) of the highest bilirubin for the occurrence of stroke was 0.71 (95% CI: 0.61-0.82) and ischemic stroke was 0.72 (95% CI: 0.57-0.91), especially in cohort studies with accepted heterogeneity (I 2 = 0). Serum total and direct bilirubin levels were significantly and positively associated with stroke severity. A stratified analysis based on gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females. While our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number: CRD42022374893).

Association of Serum Total Bilirubin and Uric Acid with Low Glomerular Filtration Rate Diabetic Kidney Disease in Type 2 Diabetic Patients.

Diabetic kidney disease (DKD) is one of the major complications of Type 2 diabetes, clinically characterized by a progressive increase in albuminuria and/or a subsequent decline in glomerular filtration rate. Identification of novel risk factors contributes to reduction in the risk of diabetic kidney disease. Bilirubin, as an antioxidant and anti-inflammatory molecule, is believed to have a protective role in kidney disease. On the other hand, uric acid is implicated in the pathogenesis of DKD due to its pro-oxidant and pro-inflammatory property in vascular tissues. A hospital based comparative cross-sectional study was conducted from October 2020 to March 2021 on 200 eligible Type 2 diabetic patients (58 with DKD and 142 without DKD) to assess the association of serum total bilirubin and serum uric acid levels with low GFR diabetic kidney disease using consecutive sampling technique. The serum total bilirubin level was significantly decreased (0.15±2.29, mean±SD) in the DKD group compared to the non-DKD group (0.19±2.26), whereas the mean±SD serum uric acid was significantly increased in the DKD group (7.13±2.21) compared to the non-DKD group (5.24±1.92). A low serum total bilirubin level was significantly associated with increased risk of DKD in multivariate analysis (AOR=2.23, 95% CI=1.55-4.13) also to high serum uric acid levels (AOR=2.09, 95% CI=1.06-4.12). Moreover, a low serum total bilirubin level was significantly associated with increased risk of DKD among patients with high serum uric acid (AOR=2.55, 95% CI=1.05-6.19). Similarly, high serum uric acid was significantly associated with increased risk of DKD among patients with low serum total bilirubin (AOR=3.49, 95% CI=1.29-9.42). Co-presence of low serum total bilirubin and high serum uric acid may be useful for stratification of DKD risk among patients with Type 2 diabetes mellitus.

Associations of Liver Function Parameters with New-Onset Hyperuricemia in a Large Taiwanese Population Study.

Hyperuricemia is the chief cause of gout and has been linked with hypertension, cardiovascular and renal disease, diabetes and metabolic syndrome. Liver with the highest protein expression of xanthine oxidase, the main enzyme responsible for uric acid formation, is the primary site of uric acid biosynthesis. However, there are few studies that examine the association between liver function and new-onset hyperuricemia. Hence, using the Taiwan Biobank dataset, we aimed to explore the capability of liver function parameters, including gamma-glutamyl transferase, total bilirubin, albumin, alanine aminotransferase and aspartate aminotransferase in association with the subsequent development of hyperuricemia. We analyzed 21,030 participants without hyperuricemia at baseline. Hyperuricemia was defined as a uric acid concentration &gt; 6.0 mg/dL in women or &gt;7.0 mg/dL in men. New-onset hyperuricemia was defined as participants without baseline hyperuricemia having developed hyperuricemia upon subsequent exam. Overall, 1804 (8.6%) of the study subjects developed new-onset hyperuricemia. After multivariable analysis, significant associations were found between the male sex (odds ratio [OR], 4.412; p &lt; 0.001), high values of systolic blood pressure (SBP) (OR, 1.006; p = 0.012), body mass index (BMI) (OR, 1.064; p &lt; 0.001), fasting glucose (OR, 1.005; p &lt; 0.001), triglycerides (OR, 1.001; p = 0.003), uric acid (OR, 5.120; p &lt; 0.001), low values of estimated glomerular filtration rates (eGFR) (OR, 0.995; p &lt; 0.001), total bilirubin (OR, 0.616; p &lt; 0.001) and new-onset hyperuricemia. The cutoff level of total bilirubin, according to the Youden index, of receiver operating characteristic curve for identifying new-onset hyperuricemia was 0.65 mg/dL. Low total bilirubin was defined as ≤0.65 mg/dL. After multivariable analysis, we found a significant association between low total bilirubin level (≤0.65 mg/dL) (OR = 0.806; p &lt; 0.001) and new-onset hyperuricemia. Our present study demonstrated that in addition to male sex, high SBP, BMI, fasting glucose, triglycerides, and uric acid and low eGFR, the serum's total bilirubin levels were negatively associated with new-onset hyperuricemia in a large Taiwanese cohort.

Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis

BackgroundBilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients.MethodsAfter identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels.ResultsForty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: − 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD − 0.30 [95%CI: − 0.56, − 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = − 0.17 [95% CI: − 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: − 8.164 [− 14.531, − 1.769]; p = 0.016) in MI patients.ConclusionPrognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis.

The role of hepatic and renal functions in the development of retinopathy of prematurity: Is proteinuria a new risk factor?

To investigate the association of hepatic and renal parameters with the development of retinopathy of prematurity (ROP) in premature infants with a gestational age ≤ 32weeks. Medical records of 240 preterm infants were reviewed retrospectively, 85 of them were grouped as type 1, type 2 ROP, and control group. The 4th week hepatic and renal function test results of the groups, on the day of their first ROP examinations, were compared for the risk of development of ROP and the development of type 1 ROP. In this study, 12, 35, and 38 infants were enrolled in the type 1, type 2 ROP, and control group, respectively. The average gestational age and birth weight were higher; however, the duration of oxygen treatment was lower in the control group (p < 0.001). The blood glucose level was significantly higher in the type 1 ROP group than in the other groups (p = 0.023). The mean of total serum bilirubin of the type 1 ROP group was significantly lower than those of the type 2 ROP and control group (p = 0.032). Proteinuria was present in 85.7% of preterms with treatment-requiring ROP and proteinuria increased the risk of ROP by 3.9 times (OR with 95% CI 3.9 (1.19-12.75), p = 0.042). We found significantly higher blood glucose and lower total bilirubin level in the type 1 ROP group. Moreover, our findings suggest that proteinuria may not be only a comorbidity factor but also related to a higher frequency of ROP and type 1 ROP in preterm infants.

Clinical characteristics and surgical outcomes of resectable acinar cell carcinoma of the pancreas-propensity score matching analysis with pancreatic ductal adenocarcinoma

BackgroundSurgical resection is recommended for patients with resectable acinar cell carcinoma (ACC). The aim of this study was to investigate the clinical characteristics and surgical outcomes of resectable ACC in comparison to pancreatic ductal adenocarcinoma (PDAC). MethodA retrospective analysis was performed on all patients who consecutively underwent radical resection with pathologically confirmed ACC and PDAC from December 2011 to December 2018. Clinicopathologic characteristics and follow-up information were analyzed. A 1:3 propensity score matching (PSM) method was used to minimize the bias between ACC and PDAC. ResultsA total of 26 patients with ACC and 1351 with PDAC were included. Compared to PDAC, ACC tended to be larger (4.5 vs. 3.0 cm; p < 0.001) and more frequently located in the pancreatic body/tail (61.5% vs. 36.6%, p = 0.009), with lower total bilirubin levels, lower neutrophil lymphocyte ratio (NLR) levels and lower carbohydrate antigen 19-9 (CA19-9) levels and carcinoembryonic antigen (CEA) levels. There was no difference in postoperative morbidities in patients with ACC and PDAC. The median OS and RFS were longer in ACC when compared to PDAC (OS: 43.5 mo vs. 19.0 mo, p = 0.004; RFS: 24.5 mo vs. 11.6 mo, p = 0.023). After the 1:3 PSM, ACC remained to be a better histological type for OS (p = 0.024), but had comparable RFS with PDAC (p = 0.164). ConclusionPatients with ACC after radical resection had better OS than that with PDAC. However, ACC is also an aggressive tumor with a similar trend of RFS with PDAC after the matching, necessitating the multidisciplinary treatment for resectable ACC disease.