Serum Direct Bilirubin Levels Research Articles

Cord Blood Bilirubin as an Early Marker of Hyperbilirubinemia in Term and Late Preterm Newborns at 48 Hours of Life: A Prospective Cohort Study

Introduction: Jaundice is a common clinical condition present during the neonatal period, which can be either physiological or pathological. Early discharge of newborns is a common practice in our country due to medico-social and economic reasons, making post-discharge follow-up of infants challenging compared to developed countries. Aim: To determine the correlation between cord blood bilirubin levels and the occurrence of hyperbilirubinemia at 48 hours of life in newborns with a gestational age of ≥35 weeks. Materials and Methods: This cohort study was conducted in the Department of Pediatrics at Dr SMCSI Medical College, Karakonam, Trivandrum, Kerala, India, over a one-year period from June 2017 to June 2018. The exposure variables included the mother’s blood group, baby's blood group, mode of delivery, gestational age, gender, and weight of the baby. The outcome variables included cord blood and 48-hour serum total and direct bilirubin levels. The data was coded and entered into Microsoft Excel and analysed using Statistical Package for Social Science (SPSS) version 16.0. Descriptive measures were calculated, and the correlation between cord and 48- hour bilirubin levels was assessed using Pearson's correlation coefficient formula. Other statistical tests applied were chisquare test and independent t-test. Results: Total subjects of 500 (243 female and 257 were males) participants were included in the study.Among the 21 babies who underwent phototherapy, 11 were female and 10 were male, and 15 were full term and six were late preterm for their gestational age . Of the 21 babies needing phototherapy, 15 were delivered by normal vaginal delivery, and six were delivered by LSCS. Correlation between cord blood bilirubin and serum bilirubin at 48hr is 0.477 with a p-value <0.001; which indicates mild correlation between the cord blood Total Bilirubin (TB)and serum TB. A cord TB value of 1.45 mg/dL had a sensitivity of 95.2% and specificity of 32.5%. A value of 1.55 mg/dL had a sensitivity of 90.5% and specificity of 40.9%. A cord TB value of 1.65 mg/dL had a sensitivity of 66.7% and specificity of 53.9%. These findings suggest that cord bilirubin levels can be used to predict which babies require further evaluation and treatment. Conclusions: Cord blood serum bilirubin can serve as a useful screening test for predicting neonatal hyperbilirubinemia and ensuring safe post-natal hospital discharge.

Case series of progressive familial intrahepatic cholestasis type 3: Characterization of variants in ABCB4 in China.

To improve the accuracy of the diagnosis of familial progressive intrahepatic cholestasis type 3 (PFIC3, https://www.omim.org/entry/602347). Between September 2019 and March 2021, we recruited four patients with PFIC3 from two liver centers in East China. Molecular genetic findings of ATP-binding cassette subfamily B member 4 [ATP binding cassette transporter A4 (ABCB4), https://www.omim.org/entry/171060] were prospectively examined, and clinical records, laboratory readouts, and macroscopic and microscopic appearances of the liver were analyzed. Four patients experienced cholestasis, mild jaundice, and elevated levels of serum direct bilirubin, γ-glutamyltransferase, or total bile acids. All patients had moderate-to-severe liver fibrosis or biliary cirrhosis, and their liver biopsy specimens stained positive with rhodamine. Molecular immunohistochemistry revealed reduced or absent MDR3 expression in all liver specimens. A novel mutation of ABCB4 (c.1560 + 2T > A) was identified in patients with PFIC3, which is of high clinical significance and may help understand mutant ABCB4 pathogenesis. MDR3 immunohistochemistry and molecular genetic analyses of ABCB4 are essential for the accurate diagnosis of PFIC3.

Dexamethasone may affect the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Glucocorticoids are currently used for the co-therapeutic management of autoimmune hepatitis and some cholestatic diseases. Thus far, we do not know the efficacy of glucocorticoids in the treatment of parenteral nutrition-associated cholestasis. We aimed to analyze whether the administration of late postnatal dexamethasone for treating bronchopulmonary dysplasia influence the occurrence of parenteral nutrition-associated cholestasis in preterm neonates. A retrospective study was conducted for 78 preterm neonates without major anomalies (gestational age was <30 weeks, and birthweight was ≤1000 g) hospitalized in a neonatal unit. Total and direct serum bilirubin levels were measured about every two weeks for all neonates. Data including the administration of dexamethasone, intravenous nutrition, and enteral feeding were collected by at least three audits. A total of 15 preterm neonates were diagnosed with parenteral nutrition-associated cholestasis, and after stopping parenteral nutrition, the direct bilirubin value decreased to the normal level for no longer than 150 days. The prolonged duration of parenteral nutrition was a risk factor, and late postnatal dexamethasone treatment was a protective factor in reducing the incidence of parenteral nutrition-associated cholestasis. Dexamethasone treatment may reduce the occurrence of parenteral nutrition-associated cholestasis in preterm neonates.

Clinical observation of laparoscopic cholecystectomy combined with endoscopic retrograde cholangiopancreatography or common bile duct lithotripsy.

The incidence of common bile duct (CBD) stones accounts for approximately 10%-15% of all CBD diseases. Approximately 8%-20% of these patients also have gallstones with heterogenous signs and symptoms. To investigate the clinical effects of laparoscopic cholecystectomy (LC) combined with endoscopic retrograde cholangiopancreatography (ERCP) and LC with CBD excision and stone extraction in one-stage suture (LBEPS) for the treatment of gallbladder and CBD stones. Ninety-four patients with gallbladder and CBD stones were selected from our hospital from January 2018 to June 2021. They were randomly divided into study and control groups with 47 patients each. The study group underwent LC with ERCP, and the control group underwent LC with LBEPS. Surgery, recovery time of gastrointestinal function, complication rates, liver function indexes, and stress response indexes were measured pre- and postoperatively in both the groups. The durations of treatment and hospital stay were shorter in the study group than in the control group. There was no significant difference between the one-time stone removal rate between the study and control groups. The time to anal evacuation, resumption of oral feeding, time to bowel sound recovery, and time to defecation were shorter in the study group than in the control group. The preoperative serum direct bilirubin (DBIL), total bilirubin (TBIL), and alanine aminotransferase (ALT) levels were insignificantly higher in the study group than that in the control group. A day after surgery, the postoperative serum DBIL, TBIL, and ALT levels were lower than their preoperative levels in both groups, and of the two groups, the levels were lower in the study group. Although the preoperative serum adrenocorticotrophic (ACTH), cortisol (COR), epinephrine (A), and norepinephrine (NE) levels were higher in the study group than that in the control group, these differences were not significant (P > 0.05). The serum ACTH, COR, A, and NE levels in both groups decreased one day after surgery compared to the preoperative levels, but the inter-group difference was statistically insignificant. Similarly, (91.79 ± 10.44) ng/mL, A, and NE levels were lower in the study group than in the control group. The incidence of complications was lower in the study group than in the control group. LC combined with ERCP induces only a mild stress response; this procedure can decrease the risk of complications, improve liver function, and achieve and promote a faster recovery of gastrointestinal functions.

Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome.

Short bowel syndrome (SBS) is a major cause of intestinal failure (IF) that may require long-term parenteral nutrition (PN) support. However, long-term PN is accompanied by severe complications such as catheter-related blood stream infection (CRBSI) and intestinal failure-associated liver disease (IFALD), and it is associated with high healthcare costs. In this study, we characterized the plasma metabolomic profile and investigated the role of metabolism in predicting long-term PN in pediatric patients with SBS. Untargeted metabolomics was performed in plasma samples from 20 SBS patients with PN support: 6 patients had IFALD and 14 patients had no liver disease. As controls, 18 subjects without liver or intestinal diseases were included for the analysis. SBS patients had distinct plasma metabolomic signatures compared to controls, and several pathways associated with amino acid metabolism and cell death were significantly changed. The presence of IFALD in SBS was associated with alterations of metabolites mainly classified as “amino acids, peptides, and analogues” and “benzene and derivatives”. Serum direct bilirubin levels were negatively correlated with levels of uridine, skatole, and glabrol. Importantly, SBS patients with long-term PN showed significantly increased levels of glutamine compared to those in the short-term PN group. Finally, using multivariate logistic regression analysis, we developed a prediction model including glutamine and creatinine to identify pediatric SBS patients who need long-term PN support. These findings underscore the potential key role of the metabolome in SBS with IF and suggest that metabolomic profiles could be used in long-term PN assessment.

Association between bilirubin and nonalcoholic fatty liver disease in the non-obese Chinese population: a cross-sectional study.

BackgroundSerum bilirubin may play a role in preventing antioxidant and cytoprotective effects in physiological conditions. Serum bilirubin levels are inversely correlated with insulin resistance and the prevalence of cardiovascular diseases and diabetes mellitus. However, the correlation between serum bilirubin and nonalcoholic fatty liver disease (NAFLD) is unclear. NAFLD in non-obese participants may lead to serious health problems, calling for prompt recognition and early management. This study aimed at investigating the relationship between the serum bilirubin levels and NAFLD in non-obese Chinese adults.MethodsWe evaluated 4,900 non-obese subjects (body mass index <25 kg/m2) residing in Wuwei, China. The subjects received a baseline questionnaire, physical examination, abdominal ultrasonography, and laboratory check-ups. Fasting serum bilirubin was measured with an automated biochemical analyzer. NAFLD was diagnosed based on imaging findings of fatty liver disease on ultrasonography, without excessive alcohol intake and other known causes for chronic liver disease. A logistic regression model was applied to calculate the association between serum bilirubin level and NAFLD in non-obese subjects.ResultsNAFLD was diagnosed in 408 (203 men) of the subjects, and they had a mean age of 51-year-old. Non-obese NAFLD patients had lower serum direct bilirubin (DBIL) levels than control group did [2.50 (1.80–3.25) vs. 2.60 (1.90–3.50), P=0.004], but no significant differences in indirect bilirubin (IBIL) and total bilirubin (TBIL) levels of the two groups was seen (both P>0.05). After adjusting confounding factors such as age, gender, body mass index, blood glucose, and blood lipids, multivariate analysis showed serum DBIL (OR: 0.96, 95% CI: 0.83–1.11, P trend =0.6022), IBIL (OR: 1.02, 95% CI: 0.89–1.17, P trend =0.7756), and TBIL (OR: 1.00, 95% CI: 0.87–1.15, P trend =0.991) levels were not associated with NAFLD in the non-obese population. In addition, subgroup analyses (stratified according to age, gender, and medical histories of hypertension, and diabetes mellitus) suggested no independent association between NAFLD and DBIL, IBIL, or TBIL.ConclusionsOur data suggest that serum bilirubin levels are unlikely to be associated with NAFLD in non-obese subjects.

Real-life Progression of the Use of a Genetic Panel in to Diagnose Neonatal Cholestasis.

From the group of NIIC patients, whom we had previously tested with our old 18-gene panel from May 2013 to September 2017 but could not establish a definitive diagnosis, we included 191 in the retrospective reanalysis group for this study. Additionally, we recruited 124 patients with NIIC into a prospective analysis group from October 2017 to October 2019. Cholestasis was defined as a serum direct bilirubin level >1.0 mg/dL. We constructed a 61-gene panel for targeted next-generation sequencing of the patients. In the retrospective reanalysis group, we found mutations in ABCC2, MPV17, NPC1, CFTR, NR1H4, or CYP27A1 in 10 (5.2%) of the 191 patients. In the prospective analysis group, 33 (26.6%) of the 124 patients had a causative mutation in JAG1, NOTCH2, ABCC2, SLC25A13, ABCB11, POLG, NPC1, CFTR, ATP8B1, or ABCB4. The top 3 genetic diagnoses were of Alagille syndrome, neonatal Dubin-Johnson syndrome, and neonatal intrahepatic cholestasis caused by citrin deficiency, which together constitute 78.8% of the genetic causes of cholestasis in Japan. We also identified 3 genotypes associated with Crigler-Najjar syndrome type 2 in the retrospective reanalysis group. The advanced NIIC gene panel successfully uncovered molecular genetic etiologies of NIIC not only in the reanalysis group but also in the prospective cohort. Crigler-Najjar syndrome type 2 patients may be included along with NIIC patients.

Long-term oral administration of Epimedii Folium induced cholestasis in mice by interfering with bile acid transport

Ethnopharmacological relevanceEpimedii Folium (EF) is a common traditional Chinese medicine that functions as a tonifying kidney yang to strengthen bones and muscles and dispel wind dampness (limb pain, lethargy, nausea, anorexia, and loose stools). Several studies have reported the potential risk of cholestatic liver damage from EF use; however, there have been few investigations of EF-induced cholestasis, particularly the underlying mechanisms. Aims of the studyThe purpose of this study was to evaluate the risk of EF-induced cholestasis in vivo and to explore the mechanisms of action. Materials and methodsICR mice were orally administered a water extract of EF (WEF) in doses of 6.5 and 19.5 g/kg/day for 14 weeks. Liver-to-body weight ratios, body weight, histopathological examination, and biochemical analyses were performed to assess WEF-induced cholestasis in the mice. Genes associated with bile acid (BA) metabolism and transport, including sodium taurocholate cotransporting polypeptide (NTCP), cytochrome P450 8B1 (CYP8B1), bile-salt export pump (BSEP), multidrug resistance P-glycoproteins 1 (MDR1), and farnesoid X receptor (FXR), were measured at the transcript and protein levels to investigate the potential mechanisms through which cholestasis is aroused by EF. ResultsAfter administration of WEF for 14 weeks, mice in the high-dose WEF group showed poor health with an increased liver-to-body weight ratio as well as higher serum aminotransferase, alkaline phosphatase, direct bilirubin, and total BA levels. Compared with the control group, mRNA expression of NTCP and cholesterol 7a-hydroxylase (CYP7A1) increased, and levels of BSEP, MDR1, multidrug resistance-associated protein 2, and multidrug resistance-associated protein 3 decreased in the WEF-treated group. NTCP, BSEP, MDR1, and CYP8B1 showed similar mRNA and protein expression trends. ConclusionWe demonstrated that the long-term oral administration of WEF causes cholestatic liver injury in mice, which is consistent with reported clinical cases. Furthermore, we found that the destruction of BA metabolism and transport is involved in WEF-induced cholestasis. The fine-scale molecular mechanisms of WEF-induced cholestasis and the active compounds of EF need further study.

Nomogram for Persistent Post-Stroke Depression and Decision Curve Analysis.

PurposePrevious studies have shown that persistent post-stroke depression (PSD) was associated with unfavorable prognosis. The aim of this multicenter prospective study was to investigate the predictors associated with persistent PSD, develop a nomogram and validate its clinical usefulness by decision curve analysis (DCA).Patients and MethodsA total of 875 acute ischemic stroke patients from four hospitals were consecutively recruited and completed 1-year follow-ups. Sociodemographic indicators, vascular risk factors, clinical information, serum biochemical indicators and cytokines were collected on admission. The functional outcome was assessed at 1 year after stroke. Persistent depression was defined as having a presentation of depression at each follow-up points and the depressive symptoms occurring persistently since the diagnosis of depression.ResultsThere were 513 patients who experienced PSD during the 1-year follow-up, the cumulative incidence of PSD within 1 year was 58.6%. Persistent PSD was recorded in 289 patients, of which 59 (20.4%) result in unfavorable outcomes. The risk factors of persistent PSD in 1 year after stroke were the Hamilton Depression Scale-17 items (HAMD-17) score at admission, serum direct bilirubin and free serum thyroxine (FT4) level and activated partial thromboplastin time (APTT). Nomogram conducted based on these factors has a C-index (± standard deviation) of 0.655 ± 0.039, and the DCA demonstrated that the nomogram had a favorable clinical utility.ConclusionWe found that persistent depression after stroke in the first-year time course after stroke was associated with HAMD-17 score at admission, lower serum direct bilirubin and FT4 level, and APTT. A nomogram was developed with advisable clinical usefulness in our study.

The relationship between serum bilirubin levels and early neurological improvement in patients with acute ischemic stroke treated with intravenous tissue plasminogen activator

Background &amp; Objective: Acute ischemic stroke is defined as the development of sudden neurological deficits resulting from a focal injury due to vascular occlusion in the central nervous system. Intravenous tissue plasminogen activator (t-PA) therapy in these patients is an internationally accepted, evidence- based effective treatment. Previous data suggest that increased serum bilirubin may reflect the intensity of oxidative stress associated with stroke severity. This study aimed to investigate the effect of bilirubin levels on early neurological improvement after intravenous t-PA treatment and whether bilirubin is a determinant in in-hospital mortality. Methods: The determinant role of admission bilirubin levels in the severity of stroke, in-hospital mortality and early neurological improvement after intravenous t-PA was investigated. An independent association of bilirubin with mortality and neurological improvement were identified by multivariate logistic regression analysis. Results: A total of 184 ischemic stroke patients who received intravenous t-PA were included in the study. Serum direct bilirubin, indirect bilirubin, and total bilirubin of patients in the group without early improvement were significantly higher than the group with improvement (p= 0.041, p= 0.030, p= 0.026, respectively). Also, in binary logistic regression analysis, total bilirubin was found to be an independent predictor for early neurological improvement (OR 6.257, 95%CI 1.482-26.413, p=0.013). Conclusions: There was a significant relationship between the severity of the stroke and in-hospital mortality and increased serum bilirubin levels in our study. Again, there was a significant relationship between the lack of early neurological improvement after intravenous t-PA and increased serum bilirubin levels, and serum direct bilirubin levels were independent predictor of neurological improvement.

Clinical characteristics of neonatal cholestasis in a tertiary hospital and the development of a novel prediction model for mortality.

SummaryBackgroundFew studies have described the aetiologies of neonatal cholestasis, and the overall neonatal cholestasis-related mortality (NCM) rate is unclear. We investigated the aetiology and outcome of neonatal cholestasis in a tertiary hospital and developed an NCM prediction model for these patients.MethodsPatients aged <100 days with serum direct bilirubin (DB) levels of >1.0 mg/dL were retrospectively screened. Diagnostic and laboratory data during the 8-week follow-up period after enrolment between 2005 and 2020 were extracted digitally, and medical charts were reviewed manually by clinicians. Logistic regression was used to derive a prediction model for the 1-year mortality outcome of neonatal cholestasis, and performance evaluation and external validation were conducted for the NCM prediction model.FindingsWe enrolled 4028 neonates with DB of >1.0 mg/dL at least once. Prematurity and birth injury (35.4%), complex heart anomalies (18.6%), liver diseases (11.4%), and gastrointestinal anomalies (9.2%) were the most common aetiologies; 398 (9.9%) patients died before one year of age. The peak value of DB was positively correlated to the 1-year mortality rate. In the multivariate analysis, simple laboratory indices, including platelet, prothrombin time, aspartate aminotransferase, albumin, direct bilirubin, creatinine, and C-reactive protein, were independent predictors of 1-year mortality outcome of complete-case subjects. Using these laboratory indices, a logistic regression-based NCM prediction model was constructed. It showed acceptable performances on discrimination (area under the curve, 0.916), calibration (slope, 1.04) and Brier scoring (0.072). The external validation of the sample (n = 920) from two other centres also revealed similar performance profiles of the NCM model.InterpretationVarious aetiologies of neonatal cholestasis were identified in a tertiary hospital, resulting in unfavourable outcomes of a large proportion. The NCM prediction model may have the potential to help clinicians to be aware of high-risk neonatal cholestasis.

Changes and Clinical Significance of PIVKA-II in Hepatitis E Patients.

Increased protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels had been widely reported in patients with hepatocellular carcinoma (HCC) and chronic hepatitis. However, the role of PIVKA-II in hepatitis E is unclear. The aim of this study was to clarify the changes related with PIVKA-II and its clinical significance in hepatitis E. We enrolled 84 patients with hepatitis E hospitalized in two hospitals from December 2019 to June 2021. The levels of serum PIVKA-II and related serological indicators in the patients were determined to elucidate the role of PIVKA-II in hepatitis E. We observed that 59.51% (50/84) of patients showed an increase in PIVKA-II levels. Compared with the normal PIVKA-II group (<32 mAU/L), patients in the elevated PIVKA-II group (>32 mAU/L) had much higher serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), and total bile acid (TBA) levels (p < 0.05 for each). Compared with the slightly elevated PIVKA-II group (32–125 mAU/L), patients in the significantly elevated PIVKA-II group (>125 mAU/L) had much lower serum albumin, alanine aminotransferase (ALT), aspartate transaminase (AST) levels, and longer days for the hospital stay (p < 0.05 for each). The association of PIVKA-II with TBIL and DBIL was an inverted U-shaped curve with an inflection point at 199.1 mAU/L). The association of PIVKA-II with IBIL was a U-shaped curve with an inflection point at 18.6 mAU/L while the association of PIVKA-II with albumin was an inverted U-shaped curve with an inflection point at 18.6 mAU/L. With the improvement of the disease, PIVKA-II levels were gradually decreased and finally returned to normal. This trend was consistent with that of bilirubin, and a peak appeared in the third week. Therefore, findings from our study show that the increase in PIVKA-II levels can be related to the degree of hepatic insufficiency in patients with hepatitis E, wherein PIVKA-II levels are transiently increased, and the trend of change can be related to the disease course.

Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1β and IL-18 levels and repressed hepatic IL-1β, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.

Evaluation of the Effects of Co-administration of Ethanol Leaves Extracts of Andrographis paniculata Leaves and Phyllanthus amarus on Albumin, Globulin and Bilirubin in Heavy Metal Treated Albino Wistar Rats

The effect of co-administration of ethanol leaves extracts of Andrographis paniculata and Phyllanthus amarus on albumin, globulin and bilirubin in a heavy metal treated albino Wistar rats was evaluated. Twenty-five male rats (130-170g) were assigned five groups of five animals each. Groups 1,2, 3 and 5 were treated with thirty percent of the LD50 of cadmium each before administration of plant extracts. Group 1 was administrated with 400mg/kg of A.paniculata and P. amarus at 50:50 dosage ratio. Groups 2 and 3 were administered with 400mg/kg of A.paniculata and P. amarus respectively. Group 4 was neither treated with heavy metal nor administered with the leave extracts and served as normal control, but Group 5 that was treated with heavy metal without plant extracts served as positive control. The animals were all fed with commercial rat mash and with distilled water throughout three weeks of extract administration. At the end of 21 days, the result revealed a non-significant decrease in mean albumin and globulin levels in the treatment groups when compared to the normal control and positive control. But the mean serum albumin, globulin and bilirubin levels in the positive control group were highest compared to the treatment groups. The result also indicated a significant decrease in direct bilirubin in the treated group when compared to the normal and positive control groups (P&gt;0.05). Significant decrease was also recorded in the mean serum direct bilirubin level in the group 2 compared to the normal and positive control groups (P&lt;0.05). These results show that ethanol extracts ofP. amarus and A.paniculata leaves could inhibit the oxidative stress that would have been caused by cadmium toxicity, therefore, the two plants leaves are hepatoprotective in nature and could be used as an hepatoprotective agents.

Effect of various level of 5F-cumyl-pica orally gavaged to wistar rats

This research studied 5F-CUMYL-effects PICAs on white Wistar rats’ liver, kidney, and heart, as well as their biological and hematological parameters. 24 male albino rats were given orally for 14 days. Group 1 was the control; groups 2 and 3 received 5 and 50 mg/kg (bw) 5F-CUMYL-PICA. Liver and kidneys deteriorated in treated rats. Liver histological changes included inflammatory cell aggregation, cytoplasmic degeneration, karyolysis, venous congestion, hemorrhage, and edema, and steatosis degeneration. Renal tissue revealed tubule degradation and casts. Glomeruli atrophy and Bowman's space expand. Heart tissue and cardiac muscle fibers exhibited myocardial fiber degradation and inflammatory cell aggregation. Serum AST, ALT, ALP, CK, total protein, Albumin, Triglyceride, Total Bilirubin, Direct Bilirubin, Urea, Creatinine, HGB, RBC, HCT, and MCHC levels changed. According to this research, synthetic cannabis’ (5F-CUMYL-PICA) negative effects are worse on the liver and kidneys in group 3 than group 2.

Association of Neonatal Jaundice with Gut Dysbiosis Characterized by Decreased Bifidobacteriales.

Neonatal jaundice, caused by excess serum bilirubin levels, is a common condition in neonates. Imbalance in the gut microbiota is believed to play a role in the development of neonatal jaundice. Thus, we aimed to reveal the gut microbiota characteristics in neonates with jaundice. 16S rRNA gene sequencing was performed on stool samples collected on day 4 from 26 neonates with jaundice (serum total bilirubin > 15.0 mg/dL) and 17 neonates without jaundice (total serum bilirubin < 10.0 mg/dL). All neonates were born full term, with normal weight, by vaginal delivery, and were breastfed. Neonates who were administered antibiotics, had serum direct bilirubin levels above 1 mg/dL, or had conditions possibly leading to hemolytic anemia were excluded. The median serum bilirubin was 16.0 mg/dL (interquartile range: 15.5–16.8) and 7.4 mg/dL (interquartile range: 6.8–8.3) for the jaundice and non-jaundice groups, respectively. There was no difference in the alpha diversity indices. Meanwhile, in the jaundice group, linear discriminant analysis effect size revealed that Bifidobacteriales were decreased at the order level, while Enterococcaceae were increased and Bifidobacteriaceae were decreased at the family level. Bifidobacteriaceae may act preventatively because of their suppressive effect on beta-glucuronidase, leading to accelerated deconjugation of conjugated bilirubin in the intestine. In summary, neonates with jaundice had dysbiosis characterized by a decreased abundance of Bifidobacteriales.

Primary endoscopic variceal ligation reduced acute variceal bleeding events but not long-term mortality in pediatric-onset portal hypertension

Esophageal variceal bleeding (EVB) is a medical emergency in patients with portal hypertension (PHT). However, studies on the long-term outcomes of prophylactic endoscopic variceal ligation (EVL) in pediatric-onset PHT are lacking. Between 1999 and 2020, patients who received EVL in the Electronic Report System of the Pediatric Endoscopy Unit were included in this retrospective study. EVL was classified as primary prophylaxis when it was performed for esophageal varices (EVs) without previous bleeding. If it was implemented in acute EVB, the subsequent EVL was classified as secondary prophylaxis. Fifty-eight patients aged 10 months to 33 years with 31 males were included. Thirty-eight patients were classified as primary prophylaxis group, and twenty, secondary prophylaxis group. The primary prophylaxis group experienced fewer 5-year EVB events than the secondary prophylaxis group (cumulative risk: 14.4% versus 32.4%). Still, it didn't significantly affect overall survival and biliary atresia transplant-free survival. Long-term mortality was significantly associated with higher serum direct bilirubin levels (≥0.55mg/dL) and lower albumin levels (≤2.54mg/dL) at the first EVL. Aspartate aminotransferase-to-platelet ratio index (APRI) with a cut-off value of 1.24 helped to predict EV presence at the initial esophagogastroduodenoscopy (EGD) (AUROC=0.762, sensitivity 75.0%, and specificity 66.7%). Primary prophylactic EVL, despite reducing acute EVB, may not change overall survival and biliary atresia transplant-free survival. APRI > 1.24 may predict EV presence at the first EGD and help to schedule a surveillance EGD. Higher direct bilirubin and lower albumin levels at the first EVL may relate to long-term mortality.

Clinical features of sporadic hepatitis E virus infection in pregnant women in Shanghai, China

Hepatitis E virus (HEV) infection causes high mortality in pregnant women of developing regions during large outbreaks. The aim of this study was to investigate the clinical features of HEV-infected pregnant women in Shanghai, China where the epidemiology of HEV has shifted from large outbreaks to the sporadic form. Clinical data of 516 pregnant and nonpregnant child-bearing age women diagnosed with HEV infection during 2009-2020 was collected at the Shanghai Public Health Clinical center. Patients' data were analysed for clinical features and laboratory parameters accordingly. Most of the hospitalized HEV-infected pregnant women (85.23%, 127/149) showed no obvious clinical symptoms and the disease outcome was generally benign with no liver failure or maternal mortality observed in the patients. By comparison, fewer (37.21%, 32/86) of the HEV-infected nonpregnant women were asymptomatic, and five cases (5.81%, 5/86) of liver failure were observed among them. The levels of serum alanine aminotransferase, aspartate aminotransferase, total bilirubin (TBiL), direct bilirubin (DBiL) and total bile acids (TBA) were significantly higher (P < 0.05) in nonpregnant women than those of the pregnant women. We found 42.99% (46/107) births had adverse foetal/neonatal outcome. Mothers who presented with adverse foetal/neonatal outcome showed higher (P < 0.05) serum TBiL, DBiL and TBA levels than those without. We found that the clinical features of sporadic HEV infection in pregnant women in Shanghai, China are generally mild and no maternal mortality occurred. However foetal/neonatal adverse outcomes including preterm births and stillbirths were observed in HEV-infected pregnant women.

The protective effect of boric acid on cholestatic rat liver ischemia reperfusion injury.

Background/aim To evaluate the potential protective effects of boric acid (BA) in experimental cholestatic liver ischemia reperfusion (IR) injury model.Materials and methods The study included 24 female rats which were divided into 3 groups each containing 8 rats. The control group (Group 1) only received laparotomy. In the IR group (Group 2) biliary tract ligation was applied and 1 week later 45 min ischemia and 1 h reperfusion with relaparotomy without any treatment was implemented. In the treatment BA+IR group (Group 3). 1 week after the biliary ligation intraperitoneal administration of 200 mg/kg BA was given 10 min before the ischemia for 45 min and reperfusion for 1 h with relaparotomy. Liver tissue and blood samples were taken for histopathological and biochemical examination. Ischemia modified albumin (IMA), SCUBE1, total antioxidant status (TAS), and total oxidant status (TOS) levels were also examined.Results Compared to control, groups IR and BA+IR had higher serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total, and direct bilirubin levels. Albumin value was high in the control group and low in the other groups. In terms of IMA levels there was no significant difference between groups (p > 0.05). When SCUBE-1 levels were examined groups IR and BA+IR were significantly higher than the group 1. TAS was highest in the group BA+IR whereas TOS was highest in the group IR and lower in the group BA+IR. In histopathological analysis, loss of intercellular border loss in hepatocytes, diffuse nuclear pycnosis and mild to moderate neutrophilic cell infiltration were observed in the IR group. Statistically significant dissociation, hemorrhage and severe neutrophilic cell infiltration were seen in hepatocytes of rats with IR (p < 0.05). Conclusion BA has promising results in the treatment of experimental IR injury of the cholestatic liver because of its antioxidant effects. It may be used in clinical practice after more extensive studies about the effects of BA on IR injury of the cholestatic liver.

Prophylactic Use of Fluconazole in Very Premature Infants.

Objective: To evaluate the efficacy, safety, and fungal sensitivity of prophylactic fluconazole use in very premature infants.Methods: We performed a retrospective historical comparative analysis of 196 very premature infants (113 in the prophylaxis group and 83 in the rescue group). The incidence of nosocomial fungal infection (NCFI) and pathogenic fungi, their drug sensitivity, and the minimum inhibitory concentration (MIC) of fluconazole were compared between the two groups. We also analyzed differences in short-term adverse outcomes, such as drug-induced liver or renal function disruption, fungal-attributable death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), periventricular leukomalacia (PVL), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC), between the groups. The effects of the prophylactic fluconazole strategy on NCFI and short-term adverse outcomes were assessed by multivariate logistic regression.Results: Candida albicans (46.7%) and Candida glabrata (43.3%) were the main culprit pathogens causing NCFI. The incidence of NCFI was significantly lower in the prophylaxis group than in the rescue group (15.9 vs. 45.8%, P < 0.001). However, fewer fungi were completely sensitive to fluconazole (40 vs. 85%, P < 0.05) and the MIC of fluconazole was higher [16.0 (3.5 ~ 16.0) vs. 3.0 (1.0 ~ 8.0) μg/ml, P < 0.001] in the prophylaxis group than in the rescue group. Compared with the rescue group, the prophylaxis group had a lower risk of NCFI (adjusted OR 0.25; 95% CI 0.11, 0.55). Additionally, the prophylaxis group had significantly lower risks of combined outcomes (one or more complications, such as BPD, ROP needing interventions, PVL/IVH (grade > 2), NEC stage ≥2, and fungal-attributable death) (adjusted OR 0.44; 95% CI 0.21, 0.92). There was no significant difference in serum alanine transferase (ALT), aspartate transaminase (AST), creatinine (Cr), or direct bilirubin (DBIL) levels between the two groups.Conclusions: Fluconazole prophylaxis reduced NCFI and improved combined clinical outcomes in very premature infants, with no increased risks of serious short-term adverse side effects; however, the MIC of fluconazole showed significant increases. Therefore, further optimization of preventive strategies is necessary to maintain the sensitivity of fluconazole against fungal isolates.