Serum Bile Acid Levels Research Articles

Comparison of composite adverse perinatal outcomes in early- and late-onset intrahepatic cholestasis of pregnancy

Comparison of composite adverse perinatal outcomes in early- and late-onset intrahepatic cholestasis of pregnancy

The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.

Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.

New insights into the regulation of bile acids synthesis during the early stages of liver regeneration: A human and experimental study

Background and aims: Liver regeneration is essential for the preservation of homeostasis and survival. Bile acids (BAs)-mediated signaling is necessary for liver regeneration, but BAs levels need to be carefully controlled to avoid hepatotoxicity. We studied the early response of the BAs-fibroblast growth factor 19 (FGF19) axis in healthy individuals undergoing hepatectomy for living donor liver transplant. We also evaluated BAs synthesis in mice upon partial hepatectomy (PH) and acute inflammation, focusing on the regulation of cytochrome-7A1 (CYP7A1), a key enzyme in BAs synthesis from cholesterol.Methods: Serum was obtained from twelve human liver donors. Mice underwent 2/3-PH or sham-operation. Acute inflammation was induced with bacterial lipopolysaccharide (LPS) in mice fed control or antoxidant-supplemented diets. BAs and 7α-hydroxy-4-cholesten-3-one (C4) levels were measured by HPLC-MS/MS; serum FGF19 by ELISA. Gene expression and protein levels were analyzed by RT-qPCR and western-blot.Results: Serum BAs levels increased after PH. In patients with more pronounced hypercholanemia, FGF19 concentrations transiently rose, while C4 levels (a readout of CYP7A1 activity) dropped 2 h post-resection in all cases. Serum BAs and C4 followed the same pattern in mice 1 h after PH, but C4 levels also dropped in sham-operated and LPS-treated animals, without marked changes in CYP7A1 protein levels. LPS-induced serum C4 decline was attenuated in mice fed an antioxidant-supplemented diet.Conclusions: In human liver regeneration FGF19 upregulation may constitute a protective response from BAs excess during liver regeneration. Our findings suggest the existence of post-translational mechanisms regulating CYP7A1 activity, and therefore BAs synthesis, independent from CYP7A1/Cyp7a1 gene transcription.

Intrahepatic cholestasis of pregnancy and its association with preeclampsia and gestational diabetes: a retrospective analysis.

To evaluate maternal and neonatal outcomes in patients with intrahepatic cholestasis of pregnancy (ICP). Patients who gave birth in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. The study comprised 1686 patients, 54 in the ICP group and 1632 controls. Patients who had ICP after 20weeks of gestation and were monitored and delivered at our facility were enrolled. Maternal demographic and obstetric characteristics data were examined. Perinatal outcomes were also assessed. Logistic regression analysis was used to determine adverse maternal outcomes. The mean age was 29years. ART, GDM, and preeclampsia were significantly higher in the ICP group. The mean serum bile acid level was 19.3 ± 3μmol/L in the ICP group. There was a higher risk of GDM and pre-eclampsia in women with ICP compared with those without and a significant association between ICP and adverse perinatal outcomes. There was a statistically significant relation between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th-minute Apgar scores < 7, and NICU requirement. No significant relationship was found between the presence of ICP and SGA and meconium. There was a significant relationship between the presence of ICP, mode of delivery, and PPH (p < 0.05). Those with ICP had a lower gestational week and birth weight, and higher rates of cesarean delivery and PPH. ICP should prompt close monitoring and management to mitigate the potential exacerbation of adverse outcomes, including preeclampsia, GDM, and preterm birth.

The Significance of Bile in the Biliopancreatic Limb on Metabolic Improvement After Duodenal-Jejunal Bypass

IntroductionDuodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreatic limb (BPL) in metabolic improvement after DJB caused by BA reabsorption. We established a new DJB procedure to prevent bile from flowing into the BPL and aimed to elucidate the importance of bile in the BPL after DJB.MethodsOtsuka Long-Evans Tokushima Fatty rats with diabetes were divided into three groups: two DJB groups and a sham group (n = 11). Duodenal-jejunal anastomosis was performed proximal to the papilla of Vater in the DJB group (n = 11). However, the DJB-D group (n = 11) underwent a new procedure with duodenal-jejunal anastomosis distal to the papilla of Vater for preventing bile flow into the BPL.ResultsGlucose metabolism improved and weight gain was suppressed in the DJB group, but not in the DJB-D and sham groups. Serum BA level and conjugated BA concentration were elevated in the DJB group. The gut microbiota was altered only in the DJB group; the abundance of Firmicutes and Bacteroidetes decreased and that of Actinobacteria increased. However, the DJB-D group exhibited no apparent change in the gut microbiota, similar to the sham group.ConclusionBAs are essential in the BPL for metabolic improvement after DJB; they can improve the gut microbiota in these processes.Graphical

Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of cesarean section and adverse fetal outcomes. Currently, ICP diagnosis depends largely on serum levels of bile acids and lacks sensitivity and specificity for accurate diagnosis. Tongue diagnosis is an important diagnostic tool in traditional Chinese medicine (TCM) and is used in our clinic as complementary treatment and personalized medicine for ICP. However, the molecular basis of the manifestation of greasy white tongue coatings in ICP remains unknown. In this study, we performed untargeted metabolomic profiling of the serum, tongue coating, and saliva of 66 pregnant women, including 22 with ICP. The metabolomic profiles of the serum and tongue coatings showed marked differences between the two clinical groups. Forty-six differentially abundant metabolites were identified, and their relative concentrations correlated with total bile acid levels. These differential metabolites included bile acids, lipids, microbiota- and diet-related metabolites, and exposomes. Conventional biochemical markers, including serum aminotransferases and bilirubin, were not significantly increased in the ICP group, whereas the total cholesterol and triglyceride levels were significantly increased as early as the first trimester. Our data provide insights into the pathophysiology of ICP and implicate the gut-liver axis and environmental exposure. Tongue coating has the potential to be a non-invasive diagnostic approach. Further studies are required to validate the clinical utility of these findings.

Bile acid profile associated with CSF and PET biomarkers in Alzheimer’s disease

BackgroundRecent studies have shown that gut microbiota can affect the development of Alzheimer’s disease (AD) through various mechanisms. Bile acids (BAs), which are the final byproducts of cholesterol metabolism created through both the human body and gut microbiome, appear to be influenced by gut microbiota and may impact AD pathological characteristics such as the accumulation of tau and amyloid-β. We aimed to investigate the associations between various serum BAs and CSF biomarkers (including Aβ, total tau, and p-tau). Additionally, we sought to examine the longitudinal changes in brain Aβ and tau through PET imaging in relation to BAs profile.MethodsThe data of 828 subjects including 491 diagnosed with mild cognitive impairment (MCI), 119 patients diagnosed with AD, and 267 cognitively normal (CN) participants were obtained from ADNI. The baseline and longitudinal [18F] florbetapir and [18F] flortaucipir PET standard uptake value ratios (SUVR) measures were obtained to assess the accumulation of tau and Aβ. Moreover, baseline levels of serum BAs and CSF Aβ1–42, tau, and p-tau were used.ResultsAfter FDR correction we observed that five BAs level and relevant calculated ratios were associated with CSF p-tau and tau, three with CSF Aβ1–42. Furthermore, three BAs level and relevant calculated ratios were associated with the tau-PET rate of change, and two with the Aβ rate of change.ConclusionThe findings from our study suggest a correlation between altered profiles of BAs and CSF and imaging biomarkers associated with AD. These results provide supporting evidence for the link between the gut microbiome and the pathological features of AD.

Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease

ABSTRACT Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.

High-Fat Diet-Induced Decreased Circulating Bile Acids Contribute to Obesity Associated with Gut Microbiota in Mice.

The altered circulating bile acids (BAs) modulate gut microbiota, energy metabolism and various physiological functions. BA profiles in liver, serum, ileum and feces of HFD-fed mice were analyzed with normal chow diet (NCD)-fed mice after 16-week feeding. Furthermore, gut microbiota was analyzed and its correlation analysis with BA was performed. The result showed that long-term HFD feeding significantly decreased hepatic and serum BA levels, mainly attributed to the inhibition of hepatic BA synthesis and the reduced reabsorption efficiency of BAs in enterohepatic circulation. It also significantly impaired glucose and lipid homeostasis and gut microbiota in mice. We found significantly higher bile salt hydrolase activity in ileal microbes and a higher ratio of free BAs to conjugated BA content in ileal contents in HFD groups compared with NCD group mice, which might account for the activated intestinal farnesoid X receptor signaling on liver BA synthesis inhibition and reduced ileal reabsorption. The decreased circulating BAs were associated with the dysregulation of the lipid metabolism according to the decreased TGR5 signaling in the ileum and BAT. In addition, it is astonishing to find extremely high percentages of taurocholate and 12-OH BAs in liver and serum BA profiles of both groups, which was mainly attributed to the high substrate selectivity for 12-OH BAs of the intestinal BAs transporter during the ileal reabsorption of enterohepatic circulation. This study revealed a significant effect of long-term HFD feeding on the decreased circulating BA pool in mice, which impaired lipid homeostasis and gut microbiota, and collectively resulted in metabolic disorders and obesity.

Alteration of serum bile acids in amyotrophic lateral sclerosis.

Hydrophilic endogenous bile acids ursodeoxycholic acid (UDCA), tauroursodeoxycholic acid (TUDCA), and glucourosodeoxycholic acid (GUDCA) have suggested neuroprotective effects. We performed a case-control study to examine the association between ALS diagnosis and serum levels of bile acids. Sporadic and familial ALS patients, age- and sex-matched healthy controls, and presymptomatic gene carriers who donated blood samples were included. Non-fasted serum samples stored at -80°C were used for the analysis. Serum bile acid levels were measured by liquid chromatography-mass spectrometry (LC-MS). Concentrations of 15 bile acids were obtained, 5 non-conjugated and 10 conjugated, and compared between ALS versus control groups (presymptomatic gene carriers + healthy controls) using the Wilcoxon-Rank-Sum test. In total, 80 participants were included: 31 ALS (17 sporadic and 14 familial ALS); 49 controls (22 gene carriers, 27 healthy controls). The mean age was 50 years old and 50% were male. In the ALS group, 45% had familial disease with a pathogenic variant in C9orf72 (29%), TARDBP (10%), FUS (3%), and CHCHD10 (3%) genes. In the control group, 43% carried pathogenic variants: C9orf72 (27%), SOD1 (10%), and FUS (6%). The serum levels of UDCA, TUDCA, and GUDCA trended higher in the ALS group compared to controls (median 27 vs. 7 nM, 4 vs. 3 nM, 110 vs. 47 nM, p-values 0.04, 0.06, 0.04, respectively). No significant group differences were found in other bile acids serum levels. In conclusion, the serum level of UDCA, TUDCA, GUDCA trended higher in ALS patients compared to controls, and no evidence of deficiencies was found.

Investigating the Protective Effect of Ellagic Acid on Cholemic Nephropathy in Cholestatic Rats

Background: Cholemic nephropathy (CN), a renal dysfunction caused by bile acids, is a severe complication of chronic liver damage and bile duct ligation (BDL), which may lead to complete kidney failure. Objectives: This study investigated the protective effect of ellagic acid on CN in cholestatic rats. Methods: Sixty male Wistar rats weighing about 180 - 200 g were randomly divided into 6 groups for in vivo investigation. The rats were randomly divided into 5 groups of 10. Cholestasis was induced in rats by closing the bile ducts; then, the animals were treated with different doses of ellagic acid (10, 25, and 50 mg/kg). Then, the induction effect of cholestasis and the protective effects of ellagic acid on serum and urinary factors, oxidative stress indices, and histopathological changes in liver and kidney tissue were investigated. Results: Bile duct ligation in rats led to an increase in serum and urinary factors. It was also associated with increased reactive oxygen species (ROS), lipid peroxidation, glutathione (GSH) oxide form, decrease in antioxidant systems, GSH and severe histopathological changes, and fibrosis of the liver and kidney tissues. Another finding of this research was the beneficial effect of ellagic acid in improving serum and urinary factors, oxidative stress indices, and histopathological changes. Conclusions: Due to its antioxidant properties, ellagic acid can potentially serve as a novel therapeutic approach for treating kidney damage caused by increased serum levels of bile acids.

Melatonin alleviates necrotizing enterocolitis by reducing bile acid levels through the SIRT1/FXR signalling axis

Bile acids (BAs) have increasingly been implicated in the onset and progression of necrotizing enterocolitis (NEC); multiple findings have demonstrated their ability to induce damage to the intestinal epithelium, thereby exacerbating disease severity. Although we previously showed that melatonin was able to treat NEC by correcting the Treg/Th17 imbalance, the modulatory effect of melatonin on BAs remains unclear. In this study, we conducted transcriptome analysis on intestinal tissues from patients with NEC and validated these findings. Subsequently, we treated mice with melatonin alone or in combination with an agonist/inhibitor of Sirtuin 1 (SIRT1) to assess faecal and serum BA levels, the expression levels of BA transporters and regulators, and the extent of intestinal injury. Our transcriptome results indicated dysregulation of BA metabolism and abnormal expression of BA transporters in patients with NEC, which were also observed in our NEC mouse model. Furthermore, exogenous BAs were found to aggravate NEC severity in mice. Notably, melatonin effectively restored the aberrant expression of BA transporters, such as apical membrane sodium-dependent bile acid transporters (ASBT), ileal bile acid-binding protein (IBABP), and organic solute transporter-alpha (OST-α), by upregulating SIRT1 expression while reducing farnesoid X receptor (FXR) acetylation, consequently leading to decreased serum and faecal BA levels and mitigated NEC severity. Thus, we propose a potential mechanism through which melatonin reduces BA levels via the SIRT1/FXR signalling axis in an NEC mouse model. Collectively, these results highlight that melatonin holds promise for reducing BA levels and represents a promising therapeutic strategy for treating NEC.

The utility of albumin-bilirubin score in patients with intrahepatic cholestasis of pregnancy: a retrospective comparative study.

The aim of this study was to examine the utility of the albumin-bilirubin score in cases of intrahepatic cholestasis of pregnancy. A total of 413 patients (182 intrahepatic cholestasis of pregnancy, 50 suspected intrahepatic cholestasis of pregnancy, 181 healthy controls) enrolled in this study. Patients with typical pruritus and bile acid levels >10 μmol/L are defined as the intrahepatic cholestasis of pregnancy group. Patients with pruritus have the same pattern as intrahepatic cholestasis of pregnancy, but who are ultimately diagnosed with other dermatoses of pregnancy are defined as suspected intrahepatic cholestasis of pregnancy. Demographic data, laboratory parameters, and albumin-bilirubin scores were compared between three groups. Correlation analysis was performed on the albumin-bilirubin score and bile acid levels. Also, receiver operating curve analyses were performed to evaluate the predictive performance of the albumin-bilirubin score for intrahepatic cholestasis of pregnancy diagnosis. The albumin-bilirubin score of the intrahepatic cholestasis of pregnancy group was significantly higher than the other groups. A positive, weak correlation was found between the albumin-bilirubin score and bile acid levels in the intrahepatic cholestasis of pregnancy group. The receiver operating curve curve analyses showed albumin-bilirubin score has significant performance for the prediction of intrahepatic cholestasis of pregnancy in all subjects (area under the curve: 0.726, 95%CI 0.679-0.774, p<0.001) (sensitivity: 69%, specificity: 64%). The detection rate for albumin-bilirubin score was calculated as 67.3%. The positive predictive value was 3.95% (CI 2.9-5.3%), and the negative predictive value was 98.9% (CI 98.6-99.2%). This study indicated higher albumin-bilirubin score levels in the intrahepatic cholestasis of pregnancy group and a positive relationship between serum bile acid levels and albumin-bilirubin score. Therefore, albumin-bilirubin score could be a cost-effective liver function test for pregnant women with intrahepatic cholestasis of pregnancy.

Analysis of gut microecological characteristics and differences between children with biliary atresia and non-biliary atresia in infantile cholestasis.

In infants with cholestasis, variations in the enterohepatic circulation of bile acids and the gut microbiota (GM) characteristics differ between those with biliary atresia (BA) and non-BA, prompting a differential analysis of their respective GM profiles. Using 16S rDNA gene sequencing to analyse the variance in GM composition among three groups: infants with BA (BA group, n=26), non-BA cholestasis (IC group, n=37), and healthy infants (control group, n=50). Additionally, correlation analysis was conducted between GM and liver function-related indicators. Principal component analysis using Bray-Curtis distance measurement revealed a significant distinction between microbial samples in the IC group compared to the two other groups. IC-accumulated co-abundance groups exhibited positive correlations with aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, and total bile acid serum levels. These correlations were notably reinforced upon the exclusion of microbial samples from children with BA. The varying "enterohepatic circulation" status of bile acids in children with BA and non-BA cholestasis contributes to distinct GM structures and functions. This divergence underscores the potential for targeted GM interventions tailored to the specific aetiologies of cholestasis.

Evaluating the Utility of Liver Transaminases as Predictors of Feto-Maternal Outcome in Lieu of Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy: A Prospective Observational Study.

Intrahepatic Cholestasis of Pregnancy (ICP) is a disorder of the second half of pregnancy causing pruritus and abnormal liver function tests (LFT). Incidence in India is 1.2-1.5%. ICP leads to adverse feto-maternal outcomes with early delivery indicated before serum bile acids (SBA) (gold standard) and hepatic transaminases are critically high. With paucity of evidence these levels are not well defined. To determine the association of liver transaminases with pregnancy outcomes in ICP and evaluate critical levels for prediction of adverse outcomes. A prospective observational study was conducted comprising 88 pregnant women with pruritus not associated with rash. After history and examination, LFT and SBA levels were done, treatment given and followed till pregnancy termination to determine the feto-maternal outcome. The mean age of participants was 26.43 ± 3.35 years. The mean SBA, ALT and AST levels were 18.97 ± 10.320 μmol/L, 206.06 ± 45.71units/litre and 175.37 ± 101.088 units/litre respectively. 39.7% of participants were symptomatic for ICP while 38.6% responded to treatment. 34.1% underwent LSCS majorly (43.3%) formeconiumand 23.3% had foetal distress. 33% had preterm delivery. 5.68% of the neonates needed NICU admission and 6.8% had respiratory distress syndrome. The cut off for ALT on ROC curve analysis was 151.5 units/litre with AUC as 0.905, sensitivity and specificity of 89.7 and 70% respectively. ICP leads to adverse pregnancy outcomes. ALT is a promising predictor of adverse outcome and termination of pregnancy can be planned accordingly.

Cholestasis gravidarum in women in the second and third trimester of gestation, clinical and specific pharmacological treatment and its benefits

Introduction: cholestasis gravidarum is a syndrome that usually occurs in pregnant women in the second or third trimester of pregnancy and ends in the puerperium. It is clinically characterized by the presence of predominantly nocturnal pruritus that is palmoplantar at first and then generalized. Alterations in liver function with or without jaundice and elevated serum bile acid levels, biochemical cholestasis is classified as mild to moderate in severity.This pathology does not have significant consequences for the mother, but it is associated with a high risk of affecting the newborn, such as premature delivery, fetal distress, fetal arrhythmias and intrauterine death. Objective: diagnostic methods and behaviors in their pharmacological treatments that provide the best results for those patients. Methods: systematic review with qualitative database from the PUBMED platform. The articles were downloaded from the PUBMED platform and Zotero was used to make the proper citations and references. In the investigation, the population will be composed of adult female patients who were admitted to any health care unit during the second and third trimesters. Results: the PUBMED database was used with the following MESH terms (cholestasis of pregnancy) that generated 2 597 results. 28 articles were analyzed in more depth, of which 12 articles were finally selected for the final analysis. Ursodeoxycholic acid (UDCA), a beta epimer of chenodeoxycholic acid, is a more polar bile acid than primary bile acids, with substantial choleretic and multiple other chemoprotective effects. The mechanism of action is not fully understood, but studies have shown that after treatment there is a reduction in total serum bile acids in both maternal and umbilical cord serum and a qualitative change in bile acid pool. serum. When compared to all controls, UDCA was also found to be associated with a decreased incidence of preterm birth, neonatal respiratory distress, and the number of neonatal intensive care unit admissions

Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner.

Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4219 samples collected from 1180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n=660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n=578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.

Serum bile acids associate with liver volume in polycystic liver disease and decrease upon treatment with lanreotide.

Polycystic liver disease (PLD) is a common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). Bile acids may play a role in PLD pathogenesis. We performed a post-hoc exploratory analysis of bile acids in ADPKD patients, who had participated in a trial on the effect of a somatostatin analogue. Our hypothesis was that serum bile acid levels increase in PLD, and that lanreotide, which reduces liver growth, may also reduce bile acid levels. Furthermore, in PLD, urinary excretion of bile acids might contribute to renal disease. With liquid chromatography-mass spectrometry, 11 bile acids in serum and 6 in urine were quantified in 105 PLD ADPKD patients and 52 age-, sex-, mutation- and eGFR-matched non-PLD ADPKD patients. Sampling was done at baseline and after 120 weeks of either lanreotide or standard care. Baseline serum levels of taurine- and glycine-conjugated bile acids were higher in patients with larger livers. In PLD patients, multiple bile acids decreased upon treatment with lanreotide but remained stable in untreated subjects. Changes over time did not correlate with changes in liver volume. Urine bile acid levels did not change and did not correlate with renal disease progression. In ADPKD patients with PLD, baseline serum bile acids were associated with liver volume. Lanreotide reduced bile acid levels and has previously been shown to reduce liver volume. However, in this study, the decrease in bile acids was not associated with the change in liver volume.

MATERNAL AND FETAL OUTCOMES IN WOMEN RECEIVING URSODEOXYCHOLEIC ACID (UDCA) AS TREATMENT FOR INTRAHEPATIC CHOLESTASIS OF PREGNANCY (IHCP), A SINGLE CENTER EXPERIENCE: ARE WE DOING ENOUGH?

Intrahepatic cholestasis of pregnancy (IHCP) is a common type of hormonally driven cholestasis in the late second or early third trimester of pregnancy. It's a reversible condition and has a genetic predisposition. This study aimed to analyze the maternal and fetal outcomes of women being treated with Ursodeoxycholic acid (UDCA) for IHCP. Seventy-five pregnant women with IHCP were included in this observational cross-sectional study, with a study duration of one year. SPSS software version 24.0 was used to analyze the data collected by the investigating officer. Laboratory and clinical parameters were assessed at presentation and after treatment. Results showed that 92% of pregnant women with IHCP had significantly raised serum bile acid levels. However, UDCA treatment caused complete resolution of itching in 57.7% of patients, reduced to mild in 40.4%, and moderate itching in 1.9% of patients. Mean Alkaline Phosphatase and ALT levels significantly decreased after UDCA treatment, with p-values of 0.001 and 0.004, respectively. The dose of UDCA required ranged from 10-25 mg/kg/day. A positive family history of IHCP was found in 36.5% of patients, while 33% had a history of IHCP in previous pregnancies, and 16% had twin pregnancies. The incidence of early delivery was high at 98%, with a mean gestational age of 36.4 weeks. Among these early deliveries, 8% had vaginal delivery, and 92% had C-sections. The indications of delivery were intractable itching and no improvement in LFTS in 15%, PROM and fetal distress in 21%, failed induction in 31%, previous cesarean in 23%, and other reasons in 10%. The study found that 99% of babies had good APGAR scores and no morbidity. However, 1% mortality was reported due to severe IHCP in the mother. In conclusion, UDCA treatment significantly improved physical and laboratory parameters and effectively treated IHCP. Early delivery had better maternal and fetal outcomes.

Evaluation of liver functional test values in women with intrahepatic cholestasis of pregnancy

Introduction. Intrahepatic cholestasis of pregnancy is a liver disease, the diagnosis of which is based on the assessment of serum bile acid levels and liver function tests. The study aimed to assess liver function test values in women with intrahepatic cholestasis of pregnancy. Materials and methods. The study was based on a prospective cohort study of 142 clinical cases, divided into two groups according to the complication of pregnancy with cholestasis gravidarum. The research was carried out by assessing the level of liver function tests as well as by studying medical documentation. Statistical data were processed using IBM Statistics SPSS 21, MedCalc and GraphPad software. To assess sensitivity and specificity in examining model efficiency, the ROC curve was used. Results. Increased ALT and AST values were found in women with intrahepatic cholestasis of pregnancy. Alkaline phosphatase and γ-glutamyltransferase values were increased in an insignificant number of pregnant women with cholestasis gravidarum. Based on ROC curves, the sensitivity of ALT indicator in diagnosis of intrahepatic cholestasis of pregnancy was 81.7%, specificity - 81.7%; for AST the sensitivity of the indicator was 80.3%, specificity - 81.7%. Conclusions. In the study it was demonstrated significant increase of ALT and AST values in women with cholestasis gravidarum, as well as high sensitivity and specificity of these indicators in the diagnosis of intrahepatic cholestasis of pregnancy.