Serum Total Bile Acid Research Articles

Association of Serum and Fecal Bile Acid Patterns With Liver Fibrosis in Biopsy-Proven Nonalcoholic Fatty Liver Disease: An Observational Study.

No reports on both blood and fecal bile acids (BAs) in patients with nonalcoholic fatty liver disease (NAFLD) exist. We simultaneously assessed the serum and fecal BA patterns in healthy participants and those with NAFLD. We collected stool samples from 287 participants from 5 hospitals in Japan (healthy control [HC]: n = 88; mild fibrosis: n = 104; and advanced fibrosis group: n = 95). Blood samples were collected and analyzed for serum BAs and 7α-hydroxy-4-cholesten-3-one (C4)-a surrogate marker for BA synthesis ability-from 141 patients. Concentrations of BAs, including cholic acid (CA), deoxycholic acid (DCA), chenodeoxycholic acid, ursodeoxycholic acid, and lithocholic acid (LCA), were measured using liquid chromatography-mass spectrometry. The total fecal BA concentration was significantly higher in the NAFLD group with worsening of fibrosis than in the HC group. Most of the fecal BAs were secondary and unconjugated. In the fecal BA fraction, CA, DCA, chenodeoxycholic acid, ursodeoxycholic acid, and LCA were significantly higher in the NAFLD than in the HC group. The total serum BA concentration was higher in the NAFLD group with worsening of fibrosis than in the HC group. In the serum BA fraction, CA, LCA, and C4 concentrations were significantly higher in the NAFLD than in the HC group. Fecal and serum BA and C4 concentrations were high in patients with NAFLD with worsening of fibrosis, suggesting involvement of abnormal BA metabolism in NAFLD with fibrosis progression. Abnormalities in BA metabolism may be a therapeutic target in NAFLD with fibrosis.

The role of bile acid measurement in the management of intrahepatic cholestasis of pregnancy

Introduction: Intrahepatic cholestasis of pregnancy complicates 1% of pregnancies. It increases the risk of severe fetal complications significantly, including preterm delivery and stillbirth. Objective: To summarize our experience with serum total bile acid level measurement that has recently become available for clinical routine in Hungary, and to present the way of gestational cholestasis care at our university. Patients and method: In a retrospective case series, we analyse the data of 12 patients suffering from severe cholestasis of pregnancy treated between September 2020 and September 2021 at the Department of Obstetrics and Gynecology, University of Debrecen. We also determine the statistical correlation between bile acid, transaminase and bilirubin levels in severe cholestasis. Results: 1258 serum samples of 758 patients were measured. 5 of them (0.7% of all cases, 6.4% of cholestasis cases) had severe (total bile acid 40-99 mu mol/L), 7 (0.9% of all cases and 9.0% of cholestasis cases) had very severe (total bile acid >= 100 mu mol/L) disease. The average age of the 12 cases was 30.6 (21-43) years, 7 of them were primigravid. 5 of the patients had a predisposing disease in their history. 6/12 patients received ursodeoxycholic acid treatment, resulting in significant decrease in the bile acid concentrations. Bile acid and GOT (R-2 = 0,14) and bile acid and GPT (R-2 = 0,17) correlations were found to be week in severe cholestasis (n = 45). Postpartum bile acid levels showed rapid improvement. So far, 11 of the patients have delivered and 13 neonates were born, 2/12 were multiple pregnancies. Average gestational age at delivery was 37 (33-40) weeks. 3/11 (27%) were preterm deliveries. 7/8 (88%) of term deliveries were induced. Elective cesarean delivery was not indicated in any of the cases, and in only 2/11 (18%) of the cases did emergency cesarean sections become necessary during labour. No stillbirth occurred. Conclusion: Serum total bile acid measurement is an effective tool in the diagnosis and follow-up of intrahepatic cholestasis of pregnancy, and is inevitable for the protocoll-based obstetrical management of patients. We also present the local protocol of our Department for the management of obstetrical cholestasis.

Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study.

ObjectiveTo establish pregnancy‐specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations.DesignCross‐sectional study.SettingTertiary‐care university hospital.PopulationHealthy pregnant women at term admitted to the Obstetrics Department over a period of 1 year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any coexisting condition of increased risk for ICP.MethodsBoth fasting (after 8–14 h of fasting) and postprandial (2 h after meal) TSBA concentrations were measured in 612 women (with 528 fasting samples and 377 postprandial samples) by automated enzymatic spectrophotometric assay.Main outcome measuresFasting and postprandial TSBA concentrations in 612 women.ResultsReference intervals of 4.4–14.1 μmol/L for fasting TSBA and 4.7–20.2 μmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting values, with a median increase of 1.0 μmol/L (p < 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as correlations with fetal sex, parity and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values measured in the winter season (p < 0.01 and 0.02, respectively)ConclusionsNormal pregnancy is associated with mild hypercholanaemia, and therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limits observed in our healthy pregnant population (14 μmol/L for fasting TSBA and 20 μmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial measurement is essential for the assessment of severity, it is recommended to measure both values rather than use random sampling.Tweetable abstractNormal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP.

The Association of Serum Total Bile Acids With Bone Mineral Density in Chinese Adults Aged 20-59: A Retrospective Cross-Sectional Study.

ObjectiveAccording to a recent study, serum total bile acids (TBA) may preserve lumbar bone mineral density (BMD) in Cushing syndrome patients, and BMD is directly linked to bone health. We were interested in examining the association between TBA and in Chinese adults aged 20–59 years.MethodsWe retrospectively analyzed the physical examination results of 2,490 general healthy subjects in Hainan West Central Hospital. Femoral neck BMD and TBA were measured, and the relationship between TBA and femoral neck BMD was evaluated by curve fitting, a generalized additive model, and multiple linear regression analysis.ResultsThe fitted smooth curve and generalized additive model showed a nonlinear relationship between TBA and femoral neck BMD, and a positive correlation between TBA and femoral neck BMD was found after we made adjustments for the potential confounders.ConclusionTBA is positively associated with femoral neck BMD in Chinese adults aged 20–59 years.

Microbial Characteristics of Common Tongue Coatings in Patients with Precancerous Lesions of the Upper Gastrointestinal Tract.

The tongue coating (TC) microbiota, a crucial component of the tongue coating, illustrates a huge microbial percentage of the body that mostly includes actinobacteria, bacteroides, firmicutes, and fusobacteria. The TC microbiota is closely related to the development of upper gastrointestinal malignancies, such as oral, gastric, and esophageal cancer. Nonetheless, the microbiological characteristics of common TCs in individuals with precancerous lesions of the upper gastrointestinal tract are still unclear. Herein, we designed a case-control study, recruiting 153 PLUGT patients with four different types of TCs, including 47 white-thin, 19 white-thick, 47 yellow-thin, and 40 yellow-thick, as well as 47 volunteers as controls. To analyze microbial characteristics, 16S rRNA microbiome approaches were used. An enzyme-linked immunosorbent assay (ELISA) was employed to assess serum IL-17A and total bile acid (TBA). According to the obtained results, Leptotrichia was found to be a promising biomarker for thin as well as thick yellow coatings. In comparison to the control TC microbiota, 39 different genera developed commensal networks in common TCs. Lachnoanaerobaculum and pseudonocardia were the most striking core bacteria. Lachnoanaerobaculum positively correlated with Leptotrichia in W-thin and Y-thick coatings, with actinomyces and methylobacterium in Y-thin coatings, with Campylobacter in Y-thick coatings, and with Bradyrhizobium in W-thick and Y-thick coatings. Serum IL-17A levels were greater in cases with W-thin coating than in controls, and serum IL-17A was positively linked with Parvimonas in patients with W-thick or Y-thin coating. In Y-thin coating, the oral dominating bacteria Streptococcus was negatively linked with serum TBA. Taken together, the promoted bacteria were found to be synergistically proliferative in the TCs of PLUGT patients. The diverse TCs had distinct bacterial commensal networks, whereas the common TCs were linked by specific bacteria to serum IL-17A and TBA.

Tectorigenin ameliorated high-fat diet-induced nonalcoholic fatty liver disease through anti-inflammation and modulating gut microbiota in mice

Nonalcoholic fatty liver disease (NAFLD) is a complex pathogenesis of liver disease combined with liver inflammation and gut microbiota dysbiosis. Tectorigenin (Tg) is derived from many plants with excellent anti-inflammation activity. However, the beneficial effect of Tg on NAFLD associated with gut microbiota remained unclear. This study aimed to investigate the underlying beneficial effect of Tg on NAFLD in high-fat diet (HFD)-fed mice. Results showed that Tg alleviated lipid profiles and liver steatosis, and reduced serum lipopolysaccharide (LPS) and total bile acid (TBA) levels. Besides, RT-qPCR and Western blot suggested that Tg alleviated hepatic lipid accumulation through inhibiting the lipogenesis and promoting the lipolysis, prevented gut-derived LPS-induced liver inflammatory via restoring intestinal barrier and restraining pro-inflammatory cytokines release, meanwhile, promoted the BA circulation via activating BA receptor and promoting BA synthesis. Moreover, Tg reverted the HFD-induced gut microbial dysbiosis by promoting the growth of beneficial Akkermansia, and inhibiting the proportions of harmful microbes, including Blautia, Lachnoclostridium, Lachnospiraceae_UCG-006, Roseburia, Romboutsia and Faecalibaculum, which were highly correlated with NAFLD-related parameters in serum and liver. Thus, Tg could attenuate NAFLD through mediating the liver-gut axis, and it could be used as a dietary supplement for NAFLD treatment via its anti-inflammatory and prebiotic effects.

Serum bile acid response to oral glucose is attenuated in patients with early type 2 diabetes and correlates with 2-hour plasma glucose in individuals without diabetes.

AimTo determine the serum bile acid (BA) response to 75‐g oral glucose in individuals without diabetes, and whether this is attenuated in patients with ‘early’ type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group.MethodsForty newly diagnosed, treatment‐naïve Han Chinese T2D subjects and 40 age‐, gender‐, and body mass index‐matched controls without T2D ingested a 75‐g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor‐19 (FGF‐19), total glucagon‐like peptide‐1 (GLP‐1), and insulin, were measured before and 2 hours after oral glucose.ResultsFasting total BA levels were higher in T2D than control subjects (P < .05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF‐19 levels in control (both P < .05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects (r = −0.42, P = .006). Total GLP‐1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects.ConclusionsThe serum BA response to a 75‐g oral glucose load is attenuated in patients with ‘early’ T2D, as is the secretion of FGF‐19 and GLP‐1, while in individuals without T2D it correlates with 2‐hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism.

Effect of intrahepatic cholestasis of pregnancy on infantile food allergy: A retrospective longitudinal study cohort in Southwest China

IntroductionIntrahepatic cholestasis of pregnancy has been consistently associated with a higher incidence of adverse pregnancy outcomes. Previous studies mainly focused on the effects of intrahepatic cholestasis of pregnancy on pregnant mothers and fetuses, and few studies reported the postpartum growth and development of fetuses in pregnant women with intrahepatic cholestasis of pregnancy. The aim of this study was to investigate impact of maternal serum total bile acid levels on maternal and neonatal outcomes as well as child growth and food allergy. Material and methodsA retrospective longitudinal cohort investigation was carried out among 751 pregnant women with intrahepatic cholestasis of pregnancy at 30-32 weeks of gestation from the Longitudinal Intrahepatic Cholestasis of Pregnancy Study (LoICPS). Data on the characteristics of the mothers and neonates were collected. Infant growth data and food sensitivities were also collected. ResultsIn our cohort, the average maternal serum total bile acid level was 35.09±30.02 μmol/L, with 58.8% of mothers suffering from mild intrahepatic cholestasis of pregnancy and 29.2% suffering from severe intrahepatic cholestasis of pregnancy. Positive correlations were found between maternal serum total bile acid levels and twin pregnancy (beta-value: 11.55, 95% CI: 2.89 - 20.20. P = 0.009) and meconium stained amniotic fluid (beta-value: 14.64, 95% CI: 9.41 - 19.87. P < 0.001). In addition, the infants of mothers with severe intrahepatic cholestasis of pregnancy were more likely to be allergic to foods at 6 months. ConclusionsThis study suggested that despite pregnant women with intrahepatic cholestasis of pregnancy taking ursodeoxycholic acid tablets and cesarean section before expected date of childbirth, the perinatal outcome of newborns partially improving, the incidence of infantile food allergy was still increased.

MicroRNA-185 modulates CYP7A1 mediated cholesterol-bile acid metabolism through post-transcriptional and post-translational regulation of FoxO1

Background and aimsCholesterol 7alpha-hydroxylase (CYP7A1) is the rate limiting enzyme of the bile acid biosynthetic pathway to convert cholesterol to bile acids, which is a major output pathway for cholesterol catabolism. In this study, we aimed to assess the potential regulatory mechanisms of microRNA-185 (miR-185) in cholesterol and bile acid homeostasis. MethodsEight-week-old male ApoE KO mice fed a high-fat diet (HFD) were injected with lentiviruses encoding antisense miR-185 (miR-185-inh). Microarrays were applied to profile miR-185-regulated genes involved in bile acid metabolism. The expression of potential targets of miR-185 was validated using qPCR and Western blotting assay in human hepatoma HepG2 cells. ResultsThe administration of miR-185-inh correlated with decreased serum total bile acids levels in ApoE KO mice. Microarray gene profiling revealed that inhibition of miR-185 upregulated hepatic CYP7A1 expression in vivo, which was further validated in HepG2 cells and primary hepatic cells in vitro by overexpression or inhibition of miR-185. Furthermore, it was revealed that miR-185 regulated CYP7A1 expression via a FoxO1-involved indirect pathway and that miR-185 directly modulated FoxO1 expression by binding to its mRNA 3′UTR in a traditional post-transcriptional manner. Besides, we also observed that miR-185 regulated CYP7A1 expression by increasing p-AKT/AKT level, which induced the phosphorylation of FoxO1 and promoted FoxO1 degradation at a post-translational level. ConclusionsThis study provides convincing evidence on the critical role of miR-185 in FoxO1 modulation at both post-transcriptional and post-translational levels, which accounts for the effects on CYP7A1 gene and its mediated cholesterol-bile acid metabolism. These results suggest an important role of miR-185 as a novel atherosclerosis-protective target for drug discovery.

Study on regulation of CYP450 enzyme system to reduce liver toxicity through compatibility of Aconiti Kusnezoffii Radix Cocta with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma

Aconiti Kusnezoffii Radix Cocta is one of the most commonly used medicinal materials in Mongolian medicine. Due to the strong toxicity of Aconiti Kusnezoffii Radix Cocta, Mongolian medicine often uses Chebulae Fructus, Glycyrrhizae Radix et Rhizoma to reduce the toxicity, so as to ensure the curative effect of Aconiti Kusnezoffii Radix Cocta while ensuring its clinical curative effect, but the mechanism is not clear. The aim of this study was to investigate the effects of Chebulae Fructus, Glycyrrhizae Radix et Rhizoma and Aconiti Kusnezoffii Radix Cocta on the mRNA transcription and protein translation of cytochrome P450(CYP450) in the liver of normal rats. Male SD rats were randomly divided into negative control(NC) group, phenobarbital(PB) group(0.08 g·kg~(-1)·d~(-1)), Chebulae Fructus group(0.254 2 g·kg~(-1)·d~(-1)), Glycyrrhizae Radix et Rhizoma group(0.254 2 g·kg~(-1)·d~(-1)), Aconiti Kusnezoffii Radix Cocta group(0.254 2 g·kg~(-1)·d~(-1))and compatibility group(0.254 2 g·kg~(-1)·d~(-1),taking Aconiti Kusnezoffii Radix Cocta as the standard). After continuous administration for 8 days, the activities of total bile acid(TBA), alkaline phosphatase(ALP), amino-transferase(ALT) and aspartate aminotransferase(AST)in serum were detected, the pathological changes of liver tissue were observed, and the mRNA and protein expression levels of CYP1 A2, CYP2 C11 and CYP3 A1 were observed. Compared with the NC group, the serum ALP, ALT and AST activities in the Aconiti Kusnezoffii Radix Cocta group were significantly increased, and the ALP, ALT and AST activities were decreased after compatibility. At the same time, compatibility could reduce the liver injury caused by Aconiti Kusnezoffii Radix Cocta. The results showed that Aconiti Kusnezoffii Radix Cocta could inhibit the expression of CYP1 A2, CYP2 C11 and CYP3 A1, and could up-regulate the expression of CYP1 A2, CYP2 C11 and CYP3 A1 when combined with Chebulae Fructus and Glycyrrhizae Radix et Rhizoma. The level of translation was consistent with that of transcription. The compatibility of Chebulae Fructus and Glycyrrhizae Radix et Rhizoma with Aconiti Kusnezoffii Radix Cocta could up-regulate the expression of CYP450 enzyme, reduce the accumulation time of aconitine in vivo, and play a role in reducing toxicity, and this effect may start from gene transcription.

320 Intrahepatic cholestasis of pregnancy and associated maternal-fetal morbidity –experience of six years (2015-2020) of a terciary hospital

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is a multifactorial condition with an unknown aetiology, unique to pregnancy and typically develops in the late second or third trimester. It is characterized by generalized pruritus, associated with elevation of total serum bile acids levels (BAL) and/or aminotransferases, both resolving after delivery. Ursodeoxycholic acid is used as a first line therapy improving overall prognosis. Methods: Retrospective descriptive study was based on the analysis of the clinical processes of pregnant women diagnosed with ICP in the last six years at the Prof.

The effectiveness of small heterodimer partner and FGF 19 levels in prediction of perinatal morbidity in intrahepatic cholestasis of pregnancy

Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules responsible for controlling serum bile acid levels. We designed this study for evaluating the effects of FGF 19 and SHP in intrahepatic cholestasis of pregnancy (ICP). Fifty-six pregnant women having ICP and 20 healthy pregnant women were included in the study. The patients were followed up until delivery in terms of pregnancy-related morbidity/mortality. Serum FGF 19 and SHP levels were determined by enzyme-linked immunosorbent assay (ELISA). Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group (p: .04, p: .003, respectively). In ROC analysis, SHP level above 1995 ng/L was found effective in predicting the need for neonatal intensive care unit (ICU) follow-up with 53.8% sensitivity and 77.8% specificity. High SHP levels were correlated with perinatal morbidity, mortality and neonatal ICU hospitalisation. Impact Statement What is already known on this subject? Itching, elevated serum transaminase and serum total bile acid (TBA) levels are the most important clinical and biochemical findings of intrahepatic cholestasis of pregnancy (ICP). Fibroblast growth factor 19 (FGF19) and small heterodimer partner (SHP) are molecules – responsible for controlling serum bile acid levels. ICP is associated with preterm labour, asphyxia, foetal distress, stillbirth and preeclampsia. What do the results of this study add? Serum FGF 19 and SHP levels were significantly higher in the patient group compared to the control group. High SHP level was found effective in predicting the need for neonatal intensive care unit and showed a negative correlation with birth week and birth weight. What are the implications of these findings for clinical practice and/or further research? Checking SHP levels can help to predict perinatal mortality and morbidity. Treatments to be developed through the mechanism of action of FGF 19 and SHP can be promising in the treatment of ICP and other cholestatic liver diseases.

A novel NAD(H)-dependent 3alpha-HSDH with enhanced activity by magnesium or manganese ions

3α-Hydroxysteroid dehydrogenase (3α-HSDH) plays a crucial role in the metabolism of sex hormones and bile acids. In this study, we heterologously expressed and characterized a novel 3α-HSDH (named Sa 3α-HSDH). Substrate specificity tests showed that Sa 3α-HSDH could catalyze Glycochenodeoxycholic acid (GCDCA) and Glycoursodeoxycholic acid (GUDCA) with catalytic efficiency (kcat/Km) 40.815 and 14.616 s−1 mM−1, respectively. Sa 3α-HSDH is NAD(H) dependent according to the results of coenzyme screening, and one of mesophilic enzymes with optimum temperature 40 °C. Additionally, Sa 3α-HSDH displayed the highest activity at pH 8.5. In this study, effect of metal ions on activity was investigated, and the results showed Mn2+ (10 mM) and Mg2+ (50 mM) could significantly enhance the activity by nearly 140% and 100%, respectively. Fe2+, Cu2+, Fe3+ and K+ could enhance the activity of Sa 3α-HSDH at different levels. Meanwhile, Na+ only displayed activity-declining effect. The three-dimensional structure of Sa 3α-HSDH was predicted and displayed the well-conserved α/β folding patterns (Rossman-fold) with a central β-sheet. These results indicated that Sa 3α-HSDH would contribute to the quantitative determination of serum total bile acids and associated bioconversion.

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.

Study on plasma exosome biomarkers of pregnant women with intrahepatic cholestasis of pregnancy

Objective and aims Serum total bile acid (TBA) level as the main index for the diagnosis of intrahepatic cholestasis of pregnancy (ICP) has some limitations. The early diagnosis and new treatment of ICP still need to be further strengthened. Materials and methods Plasma samples were collected, and exosomes were isolated. Key differential proteins were screened by bioinformatics methods. ELISA method was used to detect the concentration of the key differential protein in plasma samples, and the receiver operating characteristic curve (ROC) curve was drawn to find out the best critical value. Results There were 138 differentially expressed proteins between the ICP and the normal groups by quantitative analysis. Cluster protein (CLU) was screened as a clinical validation index. The CLU concentration of plasma exosomes in the ICP group was significantly higher than that in the normal group (p < .0001). ROC curve analysis showed that the best critical point for diagnosing ICP according to the plasma exosomes CLU concentration of pregnant women was 255.28 ng/ml. In the ICP group, the best crucial point for predicting ICP with premature delivery is 286.72 ng/ml. Conclusions The plasma exosomes CLU in pregnant women with ICP is an important biomarker for clinical diagnosis and prediction of premature delivery of ICP.

Increased admission serum total bile acids can be associated with decreased 3-month mortality in patients with acute ischemic stroke

BackgroundBile acids (BAs) not only play an important role in lipid metabolism and atherosclerosis but also have antiapoptotic and neuroprotective effects. However, few studies have focused on the relationship of the total bile acid (TBA) levels with the severity and prognosis of acute ischemic stroke (AIS).ObjectivesThe aim of this study was to investigate the potential associations of the fasting serum TBA levels on admission with the stroke severity, in-hospital complication incidence and 3 -month all-cause mortality in patients with AIS.MethodsA total of 777 consecutive AIS patients were enrolled in this study and were divided into four groups according to the quartiles of the serum TBA levels on admission. Univariate and multivariate logistic regression analyses were used to explore the relationship between the fasting TBA levels and the stroke severity, in-hospital complications, and 3-month mortality in AIS patients.ResultsPatients in group Q3 had the lowest risk of severe AIS (NIHSS > 10) regardless of the adjustments for confounders (P < 0.05). During hospitalization, 115 patients (14.8%) had stroke progression (NIHSS score increased by ≥ 2), and 222 patients (28.6%) developed at least one complication, with no significant difference among the four groups (P > 0.05). There was no significant difference in the incidence of pneumonia, urinary tract infection (UTI), hemorrhagic transformation (HT), gastrointestinal bleeding (GIB), seizures or renal insufficiency (RI) among the four groups (P > 0.05). A total of 114 patients (14.7%) died from various causes (including in-hospital deaths) at the 3-month follow-up, including 42 (21.3%), 26 (13.3%), 19 (9.9%) and 27 (13.9%) patients in groups Q1, Q2, Q3 and Q4 respectively, with significant differences (P = 0.013). After adjusting for confounding factors, the risk of death decreased (P -trend < 0.05) in groups Q2, Q3, and Q4 when compared with group Q1, and the OR values were 0.36 (0.16-0.80), 0.30 (0.13-0.70), and 0.29 (0.13-0.65), respectively.ConclusionsTBA levels were inversely associated with the 3-month mortality of AIS patients but were not significantly associated with the severity of stroke or the incidence of complications.

Correlation between serum total bile acid and nonalcoholic fatty liver disease: A cross-sectional study.

Background:Nonalcoholic fatty liver disease (NAFLD) is a common component of chronic liver disease. Total bile acid (TBA) may influence the NAFLD progression through its signaling pathways. We attempted to find out if there is a correlation between TBA and NAFLD.Methods:427,507 subjects were enrolled in health examinations conducted by The First Affiliated Hospital of Wenzhou Medical University. Among them, only 67616 met the inclusion criteria. Demographic, clinical, and laboratory data were gathered from all subjects. We used multivariate logistic regression model to find the correlation between serum TBA and NAFLD after adjusting for acknowledged risk factors for NAFLD.Results:A negative correlation was found between the TBA and NAFLD after adjusting for confounders in the multivariate logistic regression model (OR: 0.80; 95% CI: 0.72, 0.88, P < 0.001). After subgroup analysis, we found the interaction between NAFLD and diabetes was significant (P = 0.043). In patients with NAFLD without diabetes, TBA showed a protective effect in NAFLD (OR: 0.75; 95% CI: 0.67, 0.85).Conclusion:TBA is protective for NAFLD, but not in patients with NAFLD and diabetes. Further studies are urgently required to completely explore the underlying mechanisms of TBA in the pathogenesis of NAFLD.

Influence of Oral Intaking Habit on Tongue Coating Microbiota in Patients with Esophageal Precancerous Lesions.

Background: Esophageal cancer (EC) is a common digestive tract tumor in China, and oral intaking habit has a great influence on the development of EC. The present study explored the correlation between oral intaking habit and tongue coating (TC) microbiota in patients with esophageal precancerous lesions (EPL) to provide a reasonable interpretation of the influence of oral intaking habit on microbial alterations in the EPL.Methods: A case-control study was designed with 123 EPL patients and 176 volunteers with mild esophagitis, and they were well matched using sex, age, and body mass index. The TC microbiota was profiled using high-throughput sequencing of the V3-V4 region of the 16S rRNA gene, and the serum levels of total bile acid (TBA) and interleukin-17α (IL-17α) were measured using enzyme-linked immunosorbent assay. Alpha diversity, community structure, and linear discriminant analysis were conducted, and Spearman correlation analysis was used to build the symbiotic network.Results: No significant differences were observed in the diversity and richness of the TC microbiota between the cases and controls (P > 0.05). TC Peptostreptococcus and Capnocytophaga were enriched in EPL patients. Stratified analysis showed that TC microbial composition was affected by both EPL and oral intaking habit; for example, Atopobium and Actinomyces were positively related to oral intaking habit scores in both the cases and controls, while Simonsiella was negatively correlated with oral intaking habit status in cases but positively correlated with oral intaking habit status in controls. Although serum TBA and IL-17α were not associated with EPL (P > 0.05), the daily-drinking cases had a higher level of serum TBA than the nondrinking cases (P < 0.05), and Helicobacter pylori (Hp) negative controls had a higher level of serum TBA than the Hp-positive controls (P < 0.05). The symbiotic networks were comprised of 71 significant correlations in the controls and 52 significant correlations in the cases.Conclusions: The development of EPL changed the TC microbiota and decreased the symbiotic complexity of the TC bacteria, which were also influenced by the cancer-related oral intaking habit. Bile acid may be a key factor mediating changes in TC microbiota.

Perinatal Outcomes of Using Ursodeoxycholic Acid to Treat Monochorionic and Dichorionic Twin Pregnancy Complicated by Intrahepatic Cholestasis of Pregnancy

To study the effect of using ursodeoxycholic acid (UDCA) to treat monochorionic and dichorionic twin pregnancies complicated by intrahepatic cholestasis of pregnancy (ICP) and to examine the differences in perinatal outcomes. A total of 406 twin-carrying pregnant women who had ICP and received care at West China Second Hospital, Sichuan University between January 1, 2015 and November 1, 2018 were included in the study. The clinical data of monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twins with ICP were analyzed. Analysis was done to compare the treatment effect for lowering serum total bile acid (TBA) and the perinatal outcomes with simple UDCA medication or combination medication. There were no statistically significant differences in TBA levels, early-onset ICP, simple UDCA medication or combination medication, neonatal Apgar score, birth weight, length of hospital stay, C-section rate, and perinatal mortality between the MCDA and the DCDA twin groups with ICP. However, maternal age, BMI, scarred uterus, in vitro fertilization-embryo transfer, preeclampsia, twin comorbidity rate of the two groups showed statistical differences. Further comparison between twin pregnancies with mildly-elevated TBA and those with severely-elevated TBA showed significant difference in preterm birth rate ( P<0.05). Simple UDCA medication or combination medication may have the same therapeutic effect on MCDA and DCDA twin pregnancies with ICP. Monochorionic twin pregnancy, twin comorbidities and pregnancy complications were still important factors affecting pregnancy outcomes of twin pregnancies with ICP. Twin pregnancies with slightly elevated TBA have been managed as severe ICP, which may be associated with increased iatrogenic preterm births.

Intrahepatic cholestasis of pregnancy: Case series of a rare disease in an African setting

Intrahepatic cholestasis of pregnancy commonly presents in the second and third trimester with unexplained pruritus sine materia, abnormal liver function tests, and/or elevated serum total bile acid concentration. Its incidence ranges from less than 1% to 27.6%, with Araucana Indians from Chile being the highest affected. Intrahepatic cholestasis of pregnancy complicates pregnancy, hence influencing its outcomes. Our series involves three cases of pruritus in pregnancy ending with one elective cesarean delivery and two emergency cesarean deliveries without any significant complications to babies as well as immediate resolution of maternal symptoms. High index of suspicion for intrahepatic cholestasis of pregnancy is of paramount importance among clinicians even in primary care setup. Prompt treatment and intervention will prevent poor perinatal outcome.