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Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase. [ABSTRACT FROM AUTHOR]

Abstract Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have been the standard treatment for patients with sensitizing EGFR mutation. However, almost all patients eventually acquire resistance to EGFR-TKIs. Therefore, easily available parameters to estimate the outcome of lung adenocarcinoma patients treated with EGFR-TKIs are in urgent need. Lung adenocarcinoma patients harbored EGFR sensitive mutant and received EGFR-TKIs as first-line or second-line treatment were recruited in the study. X-tile software were utilized to determine the optimal cut-off value of Alkaline phosphatase (ALP), direct bilirubin (DB), total bile acid (TBA), and high-density lipoprotein-cholesterol (HDL-C). The prognostic value of ALP, DB, TBA, and HDL-C for Progression-free survival (PFS) in patients were evaluated by the Kaplan-Meier curve. We applied univariate and multivariate survival analysis to identify the independent predictor for PFS in patients with EGFR-mutant advanced lung adenocarcinoma and received EGFR-TKIs. A total of 131 lung adenocarcinoma patients with a median age of 58 years old were included in the final analysis. Patients with elevated level of DB and HDL-C showed a longer PFS, while high level of ALP and TBA indicated shorter PFS in response to EGFR-TKI treatment. The multivariate survival analyses revealed a significant association of prolonged PFS with increased DB, and decreased TBA. In conclusion, these findings suggest that DB and TBA were significant independent predictors of PFS in EGFR-TKI-treated patients with advanced lung adenocarcinoma.

Background: The association between excessive serum total bile acid (TBA) and adverse perinatal outcomes in individuals with non-intrahepatic cholestasis of pregnancy (non-ICP) hypercholanemia has not been determined, and it is unclear if this link is similar to that observed in patients with ICP. Objective: To examine the adverse perinatal outcomes in two specific subcategories: those with ICP and those with non-ICP, including individuals with liver disease and asymptomatic hypercholanemia of pregnancy (AHP), at different levels of TBA. Investigate the correlation between TBA levels and adverse perinatal outcomes of ICP, liver disease, and AHP. Methods: From 2013 to 2021, pregnant women with excessive TBA levels were taken from the electronic medical record database of our hospital and categorized into three groups: ICP (n=160), liver disease (n=164), and AHP (n=650). This was done as part of a retrospective cohort research project. Multivariable regression and subgroup analyses were performed to examine the association between TBA levels and adverse perinatal outcomes in each group. Results: The study found no significant differences in adverse perinatal outcomes between the ICP and liver disease groups at different TBA levels. However, at moderate TBA levels, both groups had a higher risk of adverse perinatal outcomes than the AHP group (p < 0.017). Among liver disease cases with TBA ≥ 100 µmol/L, three cases of perinatal deaths (6.67%) associated with moderate-to-severe acute hepatitis occurred between 27 and 33 weeks of gestation. A 59% higher chance of perinatal death was found for every 10 µmol/L rise in TBA, even after significant variables and confounders were taken into account (adjusted odds ratio (aOR) = 1.59; 95% confidence interval (CI): 1.06-2.40; p=0.03). Conclusions: If a pregnant woman has moderate-to-severe liver disease and TBA ≥ 100 µmol/L, preterm termination of pregnancy (before 34 weeks) may be considered. [ABSTRACT FROM AUTHOR]

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase.

Objective: To analyze the expression significance of serum total bile acid(TBA), intercellular adhesion molecule-1 (ICAM-1) and total bilirubin (TBIL) in pregnant women with cholestasis of pregnancy and their predictive value for fetal distress. Methods: 120 pregnant women with cholestasis of pregnancy admitted to our hospital from March 2022 to October 2023 were selected as the observation group. According to the severity of the disease, they were further divided into mild group(72 cases) and severe group(48 cases). Another 120 normal pregnant women were selected as control group. The expression levels of serum TBA, ICAM-1 and TBIL were detected in all pregnant women, and the relationship between serum TBA, ICAM-1 and TBIL and liver function indexes (ALT, AST, gamma-glutamyl transpeptidyase) was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the predictive efficacy of serum TBA, ICAM-1 and TBIL in fetal distress. Results: The expression levels of serum TBA,ICAM-1 and TBIL in observation group were higher than those in control group(P<0.05). The expression levels of serum TBA, ICAM-1 and TBIL in severe group were higher than those in mild group (P<0.05). The expression levels of ALT, AST and γ-GT in serum of observation group were higher than those of control group (P<0.05). By Pearson correlation analysis, the expression levels of serum TBA, ICAM-1 and TBIL were positively correlated with liver function indexes (ALT, AST, gamma-GT) in pregnant women with cholestasis of pregnancy (P<0.05). According to ROC curve analysis, the sensitivity of serum TBA, ICAM-1 combined with TBIL in predicting the occurrence of fetal distress in pregnant women with cholestasis of pregnancy was 91.42%, the specificity was 54.83%, and the AUC was 0.921, which was higher than the AUC of single index (P<0.05). Conclusion: The expression levels of serum TBA, ICAM-1 and TBIL in pregnant women with cholestasis of pregnancy are significantly increased, which is related to the severity of the disease, and the combined prediction of fetal distress is better. [ABSTRACT FROM AUTHOR]

Abstract Background To explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders. Methods 51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression. Results Compared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p

Background: To explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders. Methods: 51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression. Results: Compared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p < 0.001), while ALT/AST was positively correlated with ARG (r = 0.133, p = 0.013). After adjustment for confounding factors, maternal serum TBA and ALT were the independent risk factor for neonatal ORN metabolic disorders [(adjusted odds ratio (AOR) = 0.379, 95%CI = 0.188–0.762, p = 0.006), (AOR = 0.441, 95%CI = 0.211–0.922, p = 0.030)]. Maternal ALT level was an independent risk factor for neonatal VAL metabolic disorders (AOR = 0.454, 95%CI = 0.218–0.949, p = 0.036). Conclusions: The levels of high TBA, ALT, AST, and low HDL, TC of maternal were associated with the risk of NHB. Maternal TBA and ALT levels were independent risk factors for NHB-related amino acid disturbances which have value as predictive makers. [ABSTRACT FROM AUTHOR]

Objective To evaluate the changes in vitamin D levels in patients with intrahepatic cholestasis of pregnancy (ICP) and to analyze the correlation between vitamin D and total bile acids (TBA) levels. Methods A total of 60 pregnant women were selected (30 in the normal group and 30 in the ICP group) . Demographic characteristics and perinatal data were recorded and collected. Serum TBA concentration, liver function, total cholesterol, triglyceride and serum 25 (OH) D levels were measured. Results No significant differences were observed in maternal age at pregnancy, body mass index (BMI）, ALT, AST, γ-glutamyltransferase levels between two groups (all P > 0.05) . The Apgar scores at 5 minutes of all newborn infants were 10. In the ICP group, the gestational age of pregnant women was younger and the birth weight of newborn infants was lower compared with those in normal group (both P < 0.05) . Serum 25 (OH) D level was (24.84±1.88）μg/L in the ICP group, lower than (31.72±2.39）μg/L in the normal group (P < 0.05) . In the ICP group, 25 (OH) D level in the umbilical vein blood was (13.61±1.24）μg/L, lower compared with (21.96±2.69）μg/L in the normal group (P < 0.01) . The 25 (OH) D level in the umbilical vein blood was positively correlated with serum 25 (OH) D level in pregnant women in both groups (normal group： r=0.763, P < 0.001； ICP group：r=0.726, P < 0.001）. In the ICP group, serum 25 (OH) D level was negatively correlated with TBA level in the ICP group (r=-0.692, P < 0.001）. There was no correlation between serum 25 (OH) D and TBA levels in normal pregnant women (P > 0.05) . There was no significant differences in serum total cholesterol and triglyceride levels between two groups (both P > 0.05) . Conclusions The vitamin D levels in serum and umbilical vein blood of pregnant women in the ICP group are lower than those of normal pregnant women, which may be related to high TBA level in ICP patients. For ICP pregnant women, supplemental dose of vitamin D may be appropriately increased to promote intrauterine development. [ABSTRACT FROM AUTHOR]

Objective To explore the value of the combined usc of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks. Methods A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC. Results TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05). Conclusions After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks. [ABSTRACT FROM AUTHOR]

Multicenter case series has reported patients with hepatic injury following COVID-19 vaccination, which raised concern for the possibility of vaccine-induced liver dysfunction. We aimed to assess the impact of COVID-19 vaccination on liver function of pregnant women, who may be uniquely susceptible to vaccine-induced liver dysfunction. We conducted a retrospective cohort study at a tertiary hospital in Shanghai, China. Vaccine administration was obtained from the electronic vaccination record. Serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total bile acid (TBA) and total bilirubin (TBIL) in early pregnancy were determined by enzymatic methods. Among the 7745 included pregnant women, 3832 (49.5%) received at least two doses of an inactivated vaccine. COVID-19 vaccination was significantly associated with higher levels of maternal serum TBA. Compared with unvaccinated pregnant women, the mean TBA levels increased by 0.17 μmol/L (β = 0.17, 95% CI, 0.04, 0.31) for women who had been vaccinated within 3 months before the date of conception. Moreover, COVID-19 vaccination was significantly associated with an increased risk of maternal hyperbileacidemia. The risk of hyperbileacidemia increased by 113% (RR = 2.13; 95% CI, 1.17-3.87) for pregnant women who had been vaccinated within 3 months before conception compared with unvaccinated pregnant women. However, when the interval from complete vaccination to conception was prolonged to more than 3 months, COVID-19 vaccination was not associated with serum TBA levels or maternal hyperbileacidemia. Our findings suggest that vaccination with inactivated COVID-19 vaccines more than 3 months before conception have no detrimental effects on maternal liver function in early pregnancy.

Abstract Background There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. The present study aimed to evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy. Method Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups. Result We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p

Copyright of Hungarian Medical Journal / Orvosi Hetilap is the property of Akademiai Kiado and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Magyar Nőorvosok Lapja is the property of Hungarian Society of Obsterics & Gynaecology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The aim of this study was to develop a noninvasive prediction model for histological stages in PBC that is simple, easy to implement, and highly accurate. Methods: A total of 114 patients with PBC were included in this study. Demographic, laboratory data and histological assessments were collected. The independent predictors of histological stages were selected to establish a noninvasive serological model. The scores of 22 noninvasive models were calculated and compared with the established model. Results: This study included 99 females (86.8%) and 15 males (13.2%). The number of patients in Scheuer's stage 1, 2, 3 and 4 was 33 (29.0%), 34 (29.8%), 16 (14.0%), and 31 (27.2%), respectively. TBA and RDW are independent predictors of PBC histological stages. The above indexes were used to establish a noninvasive model-TR score. When predicting early histological change (S1) or liver fibrosis and cirrhosis (S3-S4), the AUROC of TR score were 0.887 (95% CI, 0.809-0.965) and 0.893 (95% CI, 0.816-0.969), higher than all of the other 22 models included in this study. When predicting cirrhosis (S4), its AUROC is still as high as 0.921 (95% CI, 0.837-1.000). Conclusion: TR score is an easy, cheap and stable noninvasive model, without complex calculation formulas and tools, and shows good accuracy in diagnosing the histological stages of PBC. [ABSTRACT FROM AUTHOR]

The total bile acid (TBA) is usually used to diagnose intrahepatic cholestasis of pregnancy (ICP) as a common clinical index. Recently many research reports on the microbiota-gut-brain axis (MGB axis) suggest that bile acids have an influence on human mental illnesses such as anxiety and depression, linked closely to intestinal microbial population. However, there is still a lack of clinical data to support intrinsic relationships about human cases. In this study, we conducted a follow-up study of 25 ICP and 98 healthy pregnant women to investigate the influence of ICP disease on perinatal depression. To further explore the effect of TBA concentration, we reviewed data of another 41 ICP women then added their cross-sectional data. The results showed that ICP disease increased mental scale scores but a conventional efficient treatment by using ursodeoxycholic acid (UDCA) could not decrease scores, suggesting intrahepatic cholestasis might make some key bile acids not to be processed by gut microbiota. UDCA could not replace the function of gut microbiota for easing depression and the change of bile acid composition in intestines worsened perinatal depressive tendency through the MGB axis.

Intrahepatic cholestasis of pregnancy (ICP) is characterized by elevated total bile acids (TBA). Although elevated maternal TBA is a major risk factors for fetal morbidity and mortality, it is unclear why some fetuses are more prone to the hazardous effect of bile acids (BA) over the others. It is unclear whether fetuses are protected by placental BA uptake, or it is the fetal BA metabolism that reduces fetal BA as compared to maternal levels. Therefore, we aimed to compared TBA levels in the umbilical vein and artery to maternal TBA in women with ICP. The study included 18 women who had TBA > 40 μmol/L and their 23 fetuses. We found that the TBA level in umbilical vein was significantly lower compared to maternal TBA level. The TBA levels in umbilical vein and umbilical artery were similar. No fetus had a serious neonatal complication. Importantly, since TBA level remains low even though maternal TBA level is high the fetuses are protected from the hazardous effects of maternal BA. Our findings suggest that there is no effective metabolism of BA in the fetus and the main decrease in TBA in the fetus is related to placental BA uptake. [ABSTRACT FROM AUTHOR]

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) can cause adverse pregnancy outcomes, such as spontaneous preterm delivery and stillbirth. It is a complex disease influenced by multiple factors, including genetics and the environment. Previous studies have reported that functioning nuclear receptor subfamily 1 group H member 4 (NR1H4) plays an essential role in bile acid (BA) homeostasis. However, some novel variants and their pathogenesis have not been fully elucidated. Therefore, this research aimed to investigate the genetic characteristics of the NR1H4 gene in ICP. Methods In this study, we sequenced the entire coding region of NR1H4 in 197 pregnant women with ICP disease. SIFT and PolyPhen2 were used to predict protein changes. Protein structure modelling and comparisons between NR1H4 reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. T-tests were used to analyse the potential significant differences between NR1H4 mutations and wild types for 29 clinical features. Fisher’s test was conducted to test the significance of differences in mutation frequencies between ICP and the three databases. Results We identified four mutations: two novel missense mutations, p.S145F and p.M185L; rs180957965 (A230S); and rs147030757 (N275N). The two novel missense mutations were absent in 1029 controls and three databases, including the 1000 Genomes Project (1000G_ALL), Exome Aggregation Consortium (ExAC) and ChinaMAP. Two web-available tools, SIFT and PolyPhen2, predicted that these mutations are harmful to the function of the protein. Moreover, compared to the wild-type protein structure, the NR1H4 p.S145F and p.M185L protein structure showed a slight change in the chemical bond in two zinc finger structures. Combined clinical data indicate that the mutation group had higher levels of total bile acid (TBA) than the wild-type group. Therefore, we hypothesized that these two mutations altered the protein structure of NR1H4, which impaired the function of NR1H4 itself and its target gene and caused an increase in TBA. Conclusions To our knowledge, this is the first study to identify the novel p.S145F and p.M185L mutations in 197 ICP patients. Our present study provides new insights into the genetic architecture of ICP involving the two novel NR1H4 mutations.

Background: Voriconazole (VCZ) metabolism is influenced by many factors. Identifying independent influencing factors helps optimize VCZ dosing regimens and maintain its trough concentration (C0) in the therapeutic window.Methods: We conducted a prospective study investigating independent factors influencing VCZ C0 and the VCZ C0 to VCZ N-oxide concentration ratio (C0/CN) in younger adults and elderly patients. A stepwise multivariate linear regression model, including the IL-6 inflammatory marker, was used. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive effect of the indicator.Results: A total of 463 VCZ C0 were analyzed from 304 patients. In younger adult patients, the independent factors that influenced VCZ C0 were the levels of total bile acid (TBA) and glutamic-pyruvic transaminase (ALT) and the use of proton-pump inhibitors. The independent factors influencing VCZ C0/CN were IL-6, age, direct bilirubin, and TBA. The TBA level was positively associated with VCZ C0 (ρ = 0.176, p = 0.019). VCZ C0 increased significantly when the TBA levels were higher than 10 μmol/L (p = 0.027). ROC curve analysis indicated that when the TBA level ≥4.05 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.54–0.74) (p = 0.007) increased. In elderly patients, the influencing factors of VCZ C0 were DBIL, albumin, and estimated glomerular filtration rate (eGFR). The independent factors that affected VCZ C0/CN were eGFR, ALT, γ-glutamyl transferase, TBA, and platelet count. TBA levels showed a positive association with VCZ C0 (ρ = 0.204, p = 0.006) and C0/CN (ρ = 0.342, p < 0.001). VCZ C0/CN increased significantly when TBA levels were greater than 10 μmol/L (p = 0.025). ROC curve analysis indicated that when the TBA level ≥14.55 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.52–0.71) (p = 0.048) increased.Conclusion: TBA level may serve as a novel marker for VCZ metabolism. eGFR and platelet count should also be considered when using VCZ, especially in elderly patients.

Background: There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. The present study aimed to evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy.Method: Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups.Result: We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p < 0.01). Multiple logistic regression analysis showed that TBA level was independently and significantly associated with preeclampsia and gestational hypertension (odds ratio: 1.37, 95% confidence interval [CI]: 1.27-1.48, p = 0.001, odds ratio: 1.34, 95% confidence interval [CI]: 1.24-1.46, p = 0.005, respectively). Moreover, elevated TBA level was positively associated with the risk of severe PE and negatively with mild PE (p < 0.01). In addition, maternal serum TBA levels were negatively related to birth weight (p < 0.001).Conclusions: These results suggest that maternal serum TBA in the normal range also might be a valuable biomarker for disease severity in preeclampsia and gestational hypertension. Additionally, our results also indicate associations of serum total bile acid levels in the normal range with an increased risk of fetal growth restriction and low birth weight among offspring. These results suggest that TBA could serve as a prognostic biomarker for new-onset hypertension during pregnancy. [ABSTRACT FROM AUTHOR]

Background and Aims: Total bile acid (TBA) is associated with portal hypertension, a risk factor for post-hepatectomy liver failure (PHLF). We conducted this study to clarify whether TBA is also associated with PHLF in patients with hepatocellular carcinoma (HCC)., Methods: We recruited patients with HCC and Child-Pugh class A, who underwent liver resection, and applied multivariate analyses to identify risk factors for PHLF., Results: We analyzed data from 154 patients. The prevalence of PHLF was 14.3%. The median maximum tumor diameter was 5.1 cm (2.9-6.9 cm). The proportions of patients with elevated TBA levels (P = 0.001), severe albumin-bilirubin (AIBL) grades (P = 0.033), and low platelet counts (P = 0.031) were significantly higher within the subgroup of patients with PHLF than in the subgroup without PHLF. The multivariate analysis results suggest that TBA level (OR, 1.08; 951.03-1.14; P = 0.003) and MRI tumor diameter (OR, 1.17; 95% CI, 1.01-1.35; P = 0.038) are independent preoperative risk factors for PHLF. The TBA levels correlated with the indocyanine green retention rate at 15 minutes (P = 0.001) and the effective hepatic blood flow (P < 0.001), two markers of portal hypertension. However, TBA levels did not correlate with tumor diameter (P = 0.536)., Conclusions: Compared to ICG R15 and AIBL score, preoperative TBA was risk factor for PHLF in Chinese patients with HCC, and it may impact PHLF through its potential role as a marker of portal hypertension., Competing Interests: Declaration of competing interest None., (Copyright © 2024 AEC. Published by Elsevier España, S.L.U. All rights reserved.)

This study aimed to evaluate the relationship between intrahepatic cholestasis of pregnancy (ICP) and Vitamin D and B12 levels. The study was a retrospective, cross-sectional, case–control study that evaluated 92 ICP cases and 102 pregnant women without any additional disease. ICP cases were grouped as mild and severe according to their total bile acid (TBA) levels, and their relationship with Vitamin D and B12 levels and perinatal outcomes was evaluated. Vitamin D and B12 levels of the ICP group were significantly lower than those of the control group. There was a moderate negative correlation between TBA and Vitamin D levels and a low negative correlation between TBA and Vitamin B12 levels. Adverse neonatal outcomes were significantly higher in the severe ICP group than in the mild ICP group. What is already known on this subject? The pathophysiology of ICP, which can lead to adverse perinatal outcomes, is not yet fully understood, and there is no preventive treatment. What do the results of this study add? This study showed that Vitamins B12 and D levels were low in women with ICP and that TBA levels were negatively correlated with Vitamin D and B12 levels. What are the implications of these findings for clinical practice and/or further research? This study may guide future studies in terms of explaining the etiopathogenesis of ICP and developing treatment options. [ABSTRACT FROM AUTHOR]

Background: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse pregnancy outcomes, such as spontaneous preterm delivery and stillbirth. It is a complex disease influenced by multiple factors, including genetics and the environment. Previous studies have reported that functioning nuclear receptor subfamily 1 group H member 4 (NR1H4) plays an essential role in bile acid (BA) homeostasis. However, some novel variants and their pathogenesis have not been fully elucidated. Therefore, this research aimed to investigate the genetic characteristics of the NR1H4 gene in ICP. Methods: In this study, we sequenced the entire coding region of NR1H4 in 197 pregnant women with ICP disease. SIFT and PolyPhen2 were used to predict protein changes. Protein structure modelling and comparisons between NR1H4 reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. T-tests were used to analyse the potential significant differences between NR1H4 mutations and wild types for 29 clinical features. Fisher's test was conducted to test the significance of differences in mutation frequencies between ICP and the three databases. Results: We identified four mutations: two novel missense mutations, p.S145F and p.M185L; rs180957965 (A230S); and rs147030757 (N275N). The two novel missense mutations were absent in 1029 controls and three databases, including the 1000 Genomes Project (1000G_ALL), Exome Aggregation Consortium (ExAC) and ChinaMAP. Two web-available tools, SIFT and PolyPhen2, predicted that these mutations are harmful to the function of the protein. Moreover, compared to the wild-type protein structure, the NR1H4 p.S145F and p.M185L protein structure showed a slight change in the chemical bond in two zinc finger structures. Combined clinical data indicate that the mutation group had higher levels of total bile acid (TBA) than the wild-type group. Therefore, we hypothesized that these two mutations altered the protein structure of NR1H4, which impaired the function of NR1H4 itself and its target gene and caused an increase in TBA. Conclusions: To our knowledge, this is the first study to identify the novel p.S145F and p.M185L mutations in 197 ICP patients. Our present study provides new insights into the genetic architecture of ICP involving the two novel NR1H4 mutations. [ABSTRACT FROM AUTHOR]

Animut Tagele Tamiru,1 Bayew Kelkay Rade,1 Oumer Ali2 1Department of General Midwifery, School of Midwifery, College of Medicine and Health Sciences Comprehensive Specialized Hospital, University of Gondar, Gondar, Ethiopia; 2Department of Obstetrics and Gynecology, College of Medicine and Health Sciences Comprehensive Specialized Hospital, University of Gondar, Gondar, EthiopiaCorrespondence: Animut Tagele Tamiru P.O Box: 196 Email animuut@gmail.comBackground: Intrahepatic cholestasis of pregnancy (ICP) is a form of liver disease which is unique to pregnancy with a worldwide prevalence ranging from 0.3% and 5.6% of pregnancies. It is presented with skin pruritus and elevated total serum bile salt and liver function test with unknown etiologic agent but suggested hormonal, environmental and genetic risk factors.Case Presentation: A 31-year-old Gravida III and Para II mother came to University of Gondar specialized hospital at the outpatient clinic in January 2019 with complain of generalized pruritus along with jaundice at 24 weeks gestational age (GA). She presented with singleton and intrauterine pregnancy with a history of one neonatal loss, one living child, and elevated bilirubin, on admission blood serum test showed elevated serum transaminases, and bilirubin. At 30 weeks GA her bilirubin total and bilirubin direct tests were 4.52 mg/dl and 3.45 mg/dl respectively. At 34 weeks GA her bilirubin values became elevated. At 37 weeks GA fetal delivery was carried out via successful caesarean section with an indication of non-reassuring fetal heart rate pattern after induction with oxytocin. The outcome was stable for both mother and baby. After a two week follow up in the outpatient set up, her liver biochemistry test was normal, and free of the clinical features with normal physical growth and intact primitive reflexes of a newborn.Conclusion: Presenting with a typical marker of increased liver function tests, bilirubin values and pruritus as a clinical feature, ICP was diagnosed. After an attempt at an oxytocin induction, an effective cesarean section was performed to deliver a live female baby, weighing 2.8 kg. The case disappeared after three weeks follow up in the puerperium.Keywords: cholestasis of pregnancy, pruritus, total bile acid, North West, Ethiopia

Abstract Background Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC). Methods A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS). Results DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299–0.637, P < 0.001; HR: 0.436, 95% CI: 0.329–0.578, P < 0.001; HR: 0.206, 95% CI: 0.124–0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391–0.871, P = 0.008; HR:0.437,95% CI: 0.292–0.655, P

Background: The association between excessive serum total bile acid (TBA) and adverse perinatal outcomes in individuals with non-intrahepatic cholestasis of pregnancy (non-ICP) hypercholanemia has not been determined, and it is unclear if this link is similar to that observed in patients with ICP., Objective: To examine the adverse perinatal outcomes in two specific subcategories: those with ICP and those with non-ICP, including individuals with liver disease and asymptomatic hypercholanemia of pregnancy (AHP), at different levels of TBA. Investigate the correlation between TBA levels and adverse perinatal outcomes of ICP, liver disease, and AHP., Methods: From 2013 to 2021, pregnant women with excessive TBA levels were taken from the electronic medical record database of our hospital and categorized into three groups: ICP ( n  = 160), liver disease ( n  = 164), and AHP ( n  = 650). This was done as part of a retrospective cohort research project. Multivariable regression and subgroup analyses were performed to examine the association between TBA levels and adverse perinatal outcomes in each group., Results: The study found no significant differences in adverse perinatal outcomes between the ICP and liver disease groups at different TBA levels. However, at moderate TBA levels, both groups had a higher risk of adverse perinatal outcomes than the AHP group ( p  < 0.017). Among liver disease cases with TBA ≥ 100µmol/L, three cases of perinatal deaths (6.67%) associated with moderate-to-severe acute hepatitis occurred between 27 and 33 weeks of gestation. A 59% higher chance of perinatal death was found for every 10 µmol/L rise in TBA, even after significant variables and confounders were taken into account (adjusted odds ratio (aOR) = 1.59; 95% confidence interval (CI): 1.06-2.40; p  = 0.03)., Conclusions: If a pregnant woman has moderate-to-severe liver disease and TBA ≥ 100µmol/L, preterm termination of pregnancy (before 34 weeks) may be considered.

Background: High bile acid concentration is associated with adverse perinatal outcomes (i.e., stillbirth and preterm birth) and experimental studies indicate that thyroid hormone regulates bile acid metabolism, but this has not yet been translated to clinical data in pregnant women. We aim to explore the association of thyroid function with bile acid concentrations and the risk of gestational hypercholanemia. Methods: This study comprised 68,016 singleton pregnancies without known thyroid or hepatobiliary diseases before pregnancy and thyroid medication based on a prospective cohort. Thyroid function and serum total bile acid (TBA) were routinely screened in both early (9–13 weeks) and late pregnancy (32–36 weeks). Hypercholanemia was defined as serum TBA concentration ≥10 μmol/L. Multiple linear regression models and multiple logistic regression models were performed. Results: A higher free thyroxine (fT4) during both early or late pregnancy was associated with a higher TBA concentration and a higher risk of hypercholanemia (all p < 0.01). A higher thyrotropin (TSH) in early pregnancy was associated with a higher TBA concentration in early pregnancy (p = 0.0155), but with a lower TBA concentration during later pregnancy (p < 0.0001), and there was no association of TSH with hypercholanemia. Overt hyperthyroidism in late pregnancy was associated with a 2.12-fold higher risk of hypercholanemia ([confidence interval; CI 1.12–4.03], p = 0.021) and subclinical hyperthyroidism during later pregnancy was associated with a 1.5-fold higher risk of hypercholanemia ([CI 1.14–1.97], p = 0.0034). Sensitivity analyses indicated that a high fT4 throughout pregnancy was associated with a higher risk of hypercholanemia rather than only in early or late pregnancy. Conclusions: A higher fT4 concentration during either early or late pregnancy, but not the TSH concentration, is associated with higher TBA and a higher risk of gestational hypercholanemia. Furthermore, hyperthyroidism during pregnancy could be a novel risk factor for hypercholanemia. [ABSTRACT FROM AUTHOR]

Abstract Background Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP). Methods We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients. Results Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777. Conclusions The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.

Background: Gluconeogenesis is stimulated by low blood glucose to maintain the glucose level; it involves lipolysis (breaking down of triglycerides), release of cortisol, and production of glycerol which can be converted into glucose. Hypoglycemia is associated with Plasmodium infection in children. Glucose homeostasis also involves glycogenolysis. This work was designed to determine the possible evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density to provide the information for useful direction in the management of Plasmodium infection in children. Methods: Thirty-five (2–5 years; female – 14, male – 11) Plasmodium-infected children were recruited as test patients, while fifty (n = 50; female – 25, male – 23) age-matched children (Plasmodium-noninfected children) were recruited from the same environment as controls. Plasma cortisol and cortisol-binding globulin were measured by the ELISA; total bile acid, glycerol by spectrophotometry, glucose, and total triglycerides were measured using Cobas C111, while Plasmodium identification and density were carried out by Leishman's thin blood film technique. Results: The results obtained showed a significant increase in plasma cortisol, cortisol-binding globulin, total bile acid, and glycerol with increase in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children (P < 0.05). There was also a significant decrease in plasma glucose and total triglycerides with decrease in parasite density and in children with the parasite densities of 512 ± 4.0 and 1014 ± 6.0 than the control children (P < 0.05). Conclusion: There was evidence of gluconeogenesis in Plasmodium-infected children in relationship with the parasite density, as the results showed increase in cortisol, cortisol-binding globulin, total bile acid, and glycerol and a decrease in plasma glucose and total triglycerides.

• Elevated serum TBA levels during pregnancy were associated with an increased risk of GDM. • A dose-dependent relationship was found between the concentration of TBA and the risk of developing PROM. • Higher TBA changes across the second and third trimester contributes to developing PROM and macrosomia. We aimed to investigate the association between total bile acid (TBA) concentrations changes during the second and third trimesters and the risk of developing adverse maternal and perinatal outcomes (AMPO). A total of 1569 pregnant Chinese women were enrolled. Serum TBA concentrations were measured during the 16–18th and 29–34th weeks of gestation. Logistic regression models were performed. After multivariable adjustment, each standard deviation increase in the TBA concentrations in the second trimester was associated with a 30% (odds ratio [OR] = 1.30, 95% confidence interval [CI]: 1.13, 1.50) increased risk of gestational diabetes mellitus (GDM) and a 22% (OR = 1.22, 95% CI: 1.07, 1.63) increased risk of premature rupture of membranes (PROM). When we compared the highest and lowest quartiles of changes in the TBA Z-scores across the second and third trimesters, the adjusted ORs were 1.84 (95% CI: 1.28, 2.65) for PROM and 1.47 (95% CI: 1.07, 2.28) for macrosomia. Elevated serum TBA concentrations during pregnancy were positively associated with increased risks of GDM and PROM. Women with more drastic changes in TBA concentrations across the second and third trimesters were at a higher risk of developing PROM and macrosomia. [ABSTRACT FROM AUTHOR]

Objective: To study Clinical study of single-hole and three-hole laparoscopic cholecystectomy and changes in serum Total bile acid（TBA), alanine aminotransferase（ALT), aspartate aminotransferase（AST), prealbumin（PA） after operation. Methods:102 patients who underwent laparoscopic cholecystectomy in our hospital from September 2019 to December 2020 were selected and divided into the single-hole group（n=52） and the three-hole group（n=50） by random number table method. The three-hole group was treated with conventional three-hole laparoscopic cholecystectomy, while the single-hole group was treated with single-hole laparoscopic cholecystectomy. The operative conditions, serum TBA, ALT, AST, PA, interleukin-6（IL-6), tumor necrosis factor（TNF-α), gastrointestinal function recovery and complications were compared between the two groups. Results: After treatment, there was no significant difference in operation time between the two groups. The incision length and intraoperative blood loss in the single-hole group were significantly lower than those in the three-hole group（P<). 05). Before treatment, there was no significant difference in TBA, ALT, AST and PA between the single-well group and the three-well group. After treatment, the serum TBA, ALT, AST, and PA levels of the monopole and triopole groups increased with the passage of time, and the serum TBA, ALT, and AST levels of the monopole group were lower than those of the triopole group, and the serum PA levels of the monopole group were higher than those of the triopole group, with significant differences（P<). 05). Before treatment, there was no significant difference in IL-6 and TNF-α between the single-well group and the three-well group. After treatment, serum IL-6 and TNF-of the monopole group and the triopole group decreased with the passage of time,and the monopole group was lower than the triopole group, with significant differences（P<). 05). Postoperative bowel sound recovery time, anal exhaust time and first defecation time in the single-hole group were significantly lower than those in the three-hole group（P<). 05).Postoperative complications in the single-hole group were significantly lower than those in the three-hole group（P<). 05). Conclusion:Single-port laparoscopic cholecystectomy can effectively improve postoperative serum TBA, ALT, AST and PA levels, shorten gastrointestinal recovery, and promote patients’ recovery. [ABSTRACT FROM AUTHOR]

Objective: To analyze the relationship between serum total bile acid (TBA) level and inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-6 (IL-6)], Th17/Treg balance and maternal and infant outcomes in patients with intrahepatic cholestasis during pregnancy (ICP). Methods: 94 patients with ICP in our hospital from January 2018 to December 2020 were selected as ICP group, 90 normal pregnant women who were examined in our hospital at the same time were selected as control group. Peripheral venous blood was extracted from pregnant women in the control group on the day of physical examination and in the ICP group on the day after admission on a fasting basis in the morning, the ratio of Th17 and Treg cells was measured by flow cytometry. The serum TBA level was detected and analyzed by automatic biochemical analyzer. TNF-α, IL-6 and IL-12 levels were detected by enzyme-linked immunosorbent assay. According to the serum TBA level of ICP pregnant women, the patients were divided into low TBA group (<40 μmol/L, 58 cases) and high TBA group (≥ 40 μmol/L, 36 cases). The perinatal outcome, maternal pregnancy outcome and incidence of neonatal complications were observed in the two groups. Results: TBA, TNF-α, IL-6, IL-12, Th17, Th17/Treg in ICP group were higher than those in control group, and Treg was lower than that in control group (P<0.05). The cesarean section rate in low TBA group was lower than that in high TBA group, and the vaginal natural delivery rate was higher than that in high TBA group (P<0.05). There was no significant difference in vaginal midwifery rate between the two groups (P>0.05). The rate of fetal intrauterine growth retardation and fetal distress in low TBA group were lower than those in high TBA group (P<0.05). There was no significant difference in neonatal asphyxia rate and perinatal mortality rate between the two groups (P>0.05). The total incidence of neonatal complications in low TBA group was lower than that in high TBA group (P<0.05). Pearson linear correlation analysis showed that serum TBA was positively correlated with TNF-α, IL-6, IL-12 and Th17/Treg ratio (P<0.05). Conclusion: The higher the TBA level of patients with ICP, the higher the incidence of adverse outcomes between maternal and infant. In addition, patients with ICP have obvious inflammatory response and Th17/Treg balance, which promotes the progress of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Bile acids, amphipathic cholesterol metabolites, have been reported to have cytoprotective and neuroprotective effects in humans and animal models. The relationship of physiological serum total bile acid (TBA) levels with diabetic peripheral neuropathy (DPN), however, has not been determined. The purpose of this study was to investigate the relationship between physiological serum TBA and DPN. Patients and Methods: In total, 856 patients with type 2 diabetes mellitus (T2DM) aged 20– 89 years were enrolled in this cross-sectional study. Serum TBA was measured, and its relationship with DPN and other parameters was analyzed. Results: T2DM patients with DPN had significantly lower serum TBA compared with those without (P< 0.01). Serum TBA was negatively associated with glycated hemoglobin A1C, plateletcrit, fibrinogen, urine albumin-to-creatinine ratio, vibration perception thresholds, and prevalence of DPN, peripheral arterial disease, and diabetic foot ulceration after adjustment for age, sex, and body mass index (P< 0.01 or P< 0.05). A graded association with prevalence of DPN and increase in serum TBA quartiles was observed (P for trend < 0.01), and there was an 48.2% decreased risk of DPN in the highest quartile of serum TBA versus the lowest quartile (95% CI 0.299– 0.617; P=0.000) after multivariate adjustment. Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum TBA to indicate DPN was 2.85 μmol/L (sensitivity 77.6% and specificity 45.6%). Conclusion: These findings suggest that lower physiological serum TBA level may be associated with the prevalence of DPN in T2DM patients and may be a potential biomarker for DPN. [ABSTRACT FROM AUTHOR]

Background: Reference intervals of clinical laboratory indexes are the basis of interpretation of test results. While intrahepatic cholestasis of pregnancy (ICP) could severely threaten maternal and fetal health, reference intervals of the biomarkers serum total bile acids (TBA) and glycocholic acid (GCA) are unsatisfactory. The purpose of this study was to derive gestational age-specific reference intervals for serum TBA and GCA in a Chinese population to promote early diagnosis of ICP. Methods: A total of 416 healthy pregnant Chinese were recruited and divided into three groups by gestational age: 140 in the first trimester (1 - 13 weeks) group, 136 in the second trimester (14 - 27 weeks) group, and 140 in the third trimester (≥ 28 weeks) group. Serum TBA and GCA levels were measured respectively by cyclic enzymatic method and latex enhanced immune turbidimetry. Reference intervals were calculated with non-parametric method. Results: The reference intervals of serum TBA are 0.90 - 6.60 μmol/L, 1.20 - 9.10 μmol/L, and 1.50 - 8.90 μmol/L respectively in the first, second, and third trimester. The reference intervals of serum GCA are 0.24 - 1.14 μg/mL in the first and second trimesters (combined) and 0.00 - 2.04 μg/mL in the third trimester. Conclusions: Gestational age-specific reference intervals of serum TBA and GCA for pregnant Chinese were derived in strict accordance with CLSI C28-A3 guidelines, which will be valuable for early diagnosis of ICP. [ABSTRACT FROM AUTHOR]

Objective　 To study the difference in the first liver function indexes of newborns with different gestational ages and birth weights. Methods 　We retrospectively analyzed the the first liver function indexes including total bilirubin （ TBIL）， direct bilirubin （ DBIL）， indirect bilirubin （ IBIL）， total protein （ TP） ， albumin （ ALB）， alanine aminotransferase （ ALT）， aspartate aminotransferase （ AST）， alkaline phosphatase （ALP），g-glutamyltransferase （GGT），total bile Changes in acid （ TBA），prealbumin （ PA），cholinesterase （CHE） of 204 premature infants with different gestational ages and 206 infants with different birth weights . Then we compared and analyzed the differences of each biochemical index in each group and between groups. Results 　There were differences in the first liver function indexes of newborns with different gestational ages and birth weights：（1） Late preterm infant group，mid-term preterm infant group and extremely preterm infant group，the levels of TP and ALB decreased sequentially with the decreasing gestational ages （P < 0.05）；the levels of CHE had no statistically significant difference （P > 0.05）. The levels of DBIL and GGT in late preterm infants and midterm preterm infants were better than extremely premature infants （P < 0.05） . （ 2） Compared with normal birth weight infants，only TBA increased in low birth weight infants （P < 0.05）；Compared with very low birth weight infants，DBIL and CHE increased in normal birth weight and low birth weight infants，however，only DBIL in low birth weight infants was statistically significant （P < 0.05）. Conclusions 　For newborns with different gestational ages and birth weights，the younger the gestational age，the lighter the weight，the worse the liver function. The influence of gestational age on liver function is far greater than the influence of body weight on liver function. [ABSTRACT FROM AUTHOR]

Background: Serum bilirubin and total bile acid (TBA) levels have been reported to be strongly associated with the risk and prognosis of certain cancers. Here, we aimed to investigate the effects of pretreatment levels of serum bilirubin and bile acids on the prognosis of patients with colorectal cancer (CRC).Methods: A retrospective cohort of 1474 patients with CRC who underwent surgical resection between January 2015 and December 2017 was included in the study. Survival analysis was used to evaluate the predictive value of pretreatment levels of bilirubin and bile acids. X-Tile software was used to identify optimal cut-off values for total bilirubin (TBIL), direct bilirubin (DBIL) and TBA in terms of overall survival (OS) and disease-free survival (DFS).Results: DBIL, TBIL, and TBA were validated as significant prognostic factors by univariate Cox regression analysis for both 3-year OS and DFS. Multivariate Cox regression analyses confirmed that high DBIL, TBIL and TBA levels were independent prognostic factors for both OS (HR: 0.435, 95% CI: 0.299-0.637, P < 0.001; HR: 0.436, 95% CI: 0.329-0.578, P < 0.001; HR: 0.206, 95% CI: 0.124-0.341, P < 0.001, respectively) and DFS (HR: 0.583, 95% CI: 0.391-0.871, P = 0.008; HR:0.437,95% CI: 0.292-0.655, P <0.001; HR: 0.634, 95% CI: 0.465-0.865, P = 0.004, respectively). In addition, nomograms for OS and DFS were established according to all significant factors, and the c-indexes were 0.819 (95% CI: 0.806-0.832) and 0.835 (95% CI: 0.822-0.849), respectively.Conclusions: TBIL, DBIL and TBA levels are independent prognostic factors in colorectal cancer patients. The nomograms based on OS and DFS can be used as a practical model for evaluating the prognosis of CRC patients. [ABSTRACT FROM AUTHOR]

Purpose: Confirmation of bile excretion into the gastrointestinal tract is important to exclude biliary atresia (BA). We compared the duodenal tube test (DTT) with hepatobiliary scintigraphy (HS) for their efficiency in detecting bile secretion. Methods: The subjects of this retrospective study were 47 infants who underwent both DTT and HS to diagnose or exclude BA between January 2000 and March 2018. Results: BA was diagnosed in 32 of the 47 patients, and 7 of the remaining 15 non-BA patients underwent intraoperative cholangiography. Among the various DTT parameters, the total bile acid in duodenal fluid (DF-TBA)/serum (S) gamma-glutamyl transferase (γGTP) ratio was found to be the most specific for BA, with sensitivity and specificity of 98.0–100%, respectively. One BA patient in whom cut off values were not met was a premature infant. The sensitivity and specificity of HS were 100–56.3%, respectively. The diagnostic accuracy of the DF-TBA/S-γGTP parameter was higher than that of HS (98.6% vs. 85.1%, respectively). Conclusions: The DTT could be more a specific method than HS to detect bile excretion. Thus, the DTT should be incorporated into the multidisciplinary diagnostic approach for the differential diagnosis of BA to prevent unnecessary intraoperative cholangiography in patients who do not have BA. [ABSTRACT FROM AUTHOR]

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Background: Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP).Methods: We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients.Results: Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777.Conclusions: The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients. [ABSTRACT FROM AUTHOR]

1. Voriconazole is known to display highly variable pharmacokinetics affecting treatment efficacy and safety. This study aimed to identify the factors causing the variation of voriconazole concentration in patients with allogeneic hematopoietic stem cell transplantation. 2. The data of patients was collected, including clinical characteristics and voriconazole concentrations. A total of 5 single nucleotide polymorphisms of 3 candidate genes (CYP2C19, ABCC2, ABCG2) related to voriconazole metabolism were genotyped by MassArray method. The correlation between polymorphisms and voriconazole concentration was analyzed. 3. A total of 244 voriconazole concentrations of 43 patients were included in this study. The voriconazole concentration was significantly correlated with patients' total bile acid (p = 0.001) and cyclosporin A (p < 0.001). The median concentration of the CYP2C19 normal metabolizers was remarkably lower than poor metabolizers (0.86 vs 2.27 μg/mL). The median concentration of ABCC2 rs2273697 GG genotype carriers was significantly higher than that of GA genotype carriers (p = 0.026). 4. The variability of voriconazole concentration is partially explained by total bile acid, metabolic types of CYP2C19. The voriconazole concentration of CYP2C19 normal metabolizers is likely to be lower than 1.0 μg/mL and thus at risk of infection due to inadequate treatment. [ABSTRACT FROM AUTHOR]

Objective: To analyze the clinical effect and safety of fluvoxamine maleate tablets combined with sulfamethoxalide on the patients with schizophrenia. Methods: 182 schizophrenic patients who were treated from February 2014 to February 2018 in our hospital were divided into 99 cases in the control group and 83 cases in the research group according to the random number table method. The control group was treated with sulfamethoxalide, and the research group was treated with fluvoxamine maleate tablets on the basis of control group. Then the clinical efficacy, changes of blood lipid metabolism, level of total bile acid (TBA), positive and negative symptom scale (PANSS) score, quality of life before and after treatment and the incidence of adverse events were compared between two groups. Results: After treatment, the total effective rate in the research group was 91.57%, which was significantly higher than that in the control group (P<0.05). The fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), triglycerides (TG), total cholesterol (TC), low-density lipoprotein C (LDL-c), high-density lipoprotein C (HLD-c), and levels of TBA of both groups showed no statistically significant difference before and after treatment (P>0.05). After treatment, the PANSS scores of both groups were significantly decreased compared with those before treatment, and the quality of life scores were significantly increased compared with those before treatment, The PANSS score in the research group were significantly lower than that in the control group, while the quality of life score was significantly higher than that in the control group(P<0.05). During treatment, the incidence of weight gain, thirst and constipation showed no statistically significant difference between the two groups (P>0.05). Conclusion: Fluvoxamine maleate tablets combined with sulfamethoxalide can improve the curative effect of patients with schizophrenia, it had little effect on the glucose and lipid metabolism and liver function with good drug safety. [ABSTRACT FROM AUTHOR]

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disease uniquely occurring during pregnancy. In this study we aimed to identify novel biomarker for the diagnosis of ICP in Chinese population. 50 healthy pregnant women, 50 mild ICP patients and 48 severe ICP patients were enrolled for this study. Liver function tests, including serum total bilirubin, direct bilirubin, alanine transami-nase, aspartate aminotransferase and cholyglycine, were performed in all participants. After an overnight fast serum levels of total bile acids (TBA), matrix metalloproteinase (MMP)-2 and MMP-9 were measured, and their correlation with liver function tests were analyzed. The observed increase in serum TBA in ICP patients was not statistically significant which made it unreliable for diagnosis of ICP in Chinese population. On the other hand, both MMP-2 and MMP-9 serum levels exhibited a progressive and significant elevation in mild and severe ICP patients compared with healthy pregnant women, which also positively correlated with liver function tests. Serum levels of both MMP-2 and MMP-9 could be reliably used as laboratory abnormalities for accurate diagnosis and sensitive grading of ICP in Chinese population.

Summary: This study is aimed to evaluate the hypocholesterolaemic effect of anthocyanin extracts of lingonberry (LAE) in vitro and vivo studies. In vitro, LAE can effectively inhibit the micellisation of cholesterol with significant dose–effect relationship. In animal experiments, after 10‐weeks of LAE administration, lower values of body mass, daily food intake, liver weight, visceral adipose content, TC level, LDL‐C level, fasting blood glucose level and higher HDL‐C level in serum, cholesterol content and total bile acid content in faeces are observed in HCD‐induced hypercholesterolaemic mice compared with model group. These observations suggest that LAE could promote the metabolism of serum cholesterol in HCD‐induced hypercholesterolaemic mice primarily via faecal excretion of cholesterol. Furthermore, LAE may reduce the inflammatory cell infiltration and attenuate steatosis and hepatocellular fat deposit in the liver. Our results indicate that LAE is a potential dietary supplement in cholesterol‐lowering or for hypercholesterolaemic treatment. These findings may provide important basis for further optimisation of dietary anthocyanins utilisation. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study was to investigate the predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with dichorionic diamniotic (DCDA) twin pregnancies.Methods: This study was a retrospective study of women diagnosed with ICP and DCDA twin pregnancies in Chengdu's women and children's central hospital. These patients were subdivided into mild and severe ICP groups according to total bile acid (TBA) level. The clinical characteristics and perinatal outcomes were collected and compared between the two groups. Logistic regression analysis was developed to evaluate predictors of adverse perinatal outcomes.Results: About 134 cases were included in the study. Eighty-four cases were in the mild ICP group, and the other 50 cases were in the severe ICP group. Level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and direct bilirubin (DBIL) in the severe ICP group were significant higher than those in the mild ICP group. The rate of delivery before 34 gestational weeks, meconium-stained amniotic fluid, and composite adverse neonatal outcome were higher in the severe ICP group than those in the mild ICP group. After adjusting for confounders, ICP onset gestational age (GA) <30 weeks and AST >200U/l were associated with GA at delivery <34 weeks. ALP >400U/l was an independent risk factor of meconium-stained amniotic fluid. ICP onset GA <30 weeks was an independent risk factor of composite adverse neonatal outcome.Conclusion: ICP onset GA <30 weeks, TBA >40 µmol/l, AST >200U/l, and ALP >400U/l were associated with composite adverse perinatal outcomes in ICP with DCDA twin pregnancies. For those patients with these characteristics, fetal surveillance and treatment should be enhanced. [ABSTRACT FROM AUTHOR]