Serum Bile Acid Levels Research Articles

English

BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a multifactorial pregnancy specific liver disorder which is also known as obstetric cholestasis. The purpose of this study was to establish the value of maternal serum bile acid in diagnosis of ICP, evaluate the treatment of ICP with UDCA (ursodeoxycholic acid) and its influence on maternal and neonatal outcome. METHODS It was a cross-sectional study. 90 women diagnosed with ICP were studied for a period of 2 years and 3 months at tertiary care government hospital. Statistical analysis was performed using chi square test. ‘P’ value of < 0.05 was considered as statistically significant in this observational study. RESULTS The present study evaluates that ICP is more common in multigravida and in age group of 26 years – 30 years. It recurs in subsequent pregnancies significantly. Itching, most common symptom is commenced at 34 weeks ± 2.85 weeks. Transaminases were normal with elevated serum bile acid levels in 32.33 % cases. The mean gestational age at delivery ranged between 35 to 39 weeks. Most common mode of delivery is lower segment caesarean section (LSCS) with commonest indication as meconium-stained amniotic fluid (MSAF) and 31 babies required neonatal intensive care unit (NICU). CONCLUSIONS Precise diagnosis, follow up, target medication and active management is required. Although maternal outcome for patients is good and without any long-term sequelae, fetal outcome can be devastating. Active management with close antenatal surveillance of the fetus is usually recommended for better perinatal outcome. KEYWORDS Intrahepatic Cholestasis of Pregnancy (ICP), Ursodeoxycholic Acid (UDCA), Neonatal Intensive Care Unit (NICU), Lower Segment Caesarean Section (LSCS)

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

Malnutrition, Frailty, and Sarcopenia in Patients With Cirrhosis: 2021 Practice Guidance by the American Association for the Study of Liver Diseases.

A Retrospective Clinical Analysis of the Serum Bile Acid Alteration Caused by Traumatic Brain Injury.

Traumatic brain injury (TBI) can cause damage to peripheral organ systems, such as digestive organ system, and alterations of gut microbiota in addition to brain injury. Our previous study found that TBI induced gastrointestinal dysfunction accompanied by alterations of bile acid metabolism. Bile acid and its receptors have been reported to play important roles in various neurological diseases. To further examine the changes of bile acid metabolism in TBI patients, we performed a retrospective clinical analysis. In this study, 177 patients were included, and the results showed that TBI patients had more frequent antibiotic use compared with a control group. Regression analysis identified TBI as an independent factor for reduction of serum bile acid level (B = −1.762, p = 0.006), even with antibiotic use taken into a regression model. Sub-group regression analysis of TBI patients showed that antibiotic use was negatively associated with bile acid level, while creatinine and triglyceride were positively associated with bile acid level. In conclusion, these data indicated that TBI could greatly reduce serum bile acid. This study provided preliminary but novel clinical evidence of TBI interfering with bile acid metabolism, and further studies with large sample sizes are needed to validate these findings in the future.

Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a rare but potentially serious complication of pregnancy, the main symptom of which is intense pruritus with elevated serum levels of bile acids. The elevated serum bile acid concentration is regarded as a predictor for poor perinatal outcome including intrauterine death. Ursodeoxycholic acid (UDCA) has become established as the treatment of choice in clinical management to achieve a significant improvement in symptoms and reduce the cholestasis. Pregnant women with severe intrahepatic cholestasis should always be managed in a perinatal centre with close interdisciplinary monitoring and treatment involving perinatologists and hepatologists to minimise the markedly increased perinatal morbidity and mortality as well as maternal symptoms.

Serum Bile Acid Levels in Women With Intrahepatic Cholestasis of Pregnancy in India

Intrahepatic cholestasis of pregnancy (ICP) manifests as unexplained intense pruritus in the third trimester of pregnancyand is often diagnosed based on elevated serum bile acid measurement. There are no data from India on serum bile acid levels in pregnant women with ICP. Pregnant women with significant pruritus during the third trimester of gestation and with elevated serum alanine aminotransferase and/or aspartate aminotransferase (normal: <40 IU/L) were taken as having ICP. Serum BA levels were measured in themand in nonpregnant women and healthy pregnant women without itching. Of the 3735 pregnant women screened, 105 (2.8%) had ICP (age 28 [26-32] years; gestational age 32 [30-36] weeks; primigravida 32.3%, and 95.3% normal fetal growth). Median (interquartile range) serum bile acid levels in nonpregnant women (n= 61; 28 [25-31] years) and pregnant women without ICP (n= 59; 28 [25-31] years) were similar (3.7 [1.6-5.1] μmol/L and 3.7 [2.2-5.8] μmol/L, respectively). By comparison, serum bile acid level in women with ICP (n= 105; 28 [26-32] years) was significantly higher (20.2 [12.7-39.5] μmol/L; P< 0.05 each), being above 10μmol/L in 88 (83.8%). The optimum cut-off for the diagnosis of ICP in our population was ≥8.6μmol/L, with sensitivity of 87.6%, specificity of 93.3% and area under the receiver-operator characteristics curve of 0.937 (95% CI: 0.904-0.970). Serum BA levels in healthy Indian nonpregnant and pregnant women are similar to those in other populationsand can be used to diagnose ICP with an optimal cut-off being 8.6μmol/L.

Assessment of intrahepatic cholestasis in pregnancy and the effect of disease severity on transient tachypnea in the newborn in uncomplicated fetuses.

Considering the effects of bile-acid levels on fetal lungs and pulmonary surfactants, we hypothesized that in the presence of intrahepatic pregnancy cholestasis (ICP), poor neonatal respiratory problems are observed in relation to the severity of the disease. Delivery timing with the presence of ICP is scheduled during late-preterm and early term gestational weeks. The aim of this study was to assess ICP and disease severity effects on transient tachypnea of the newborn (TTN) in uncomplicated fetuses. This study comprised 1,097 singleton pregnant women who were separated into three groups-control, mild ICP, and severe ICP. The pregnant women diagnosed with ICP between January 2010 and September 2020 was investigated using the hospital's database. For the control group, healthy pregnant women who met the same exclusion criteria and were similar in terms of maternal age, gestational age at delivery, and mode of delivery were analyzed. The TTN rate was 14.5% in the severe ICP group, 6.5% in the mild ICP group, and 6.2% in the control group. The TTN rate in the severe ICP group was significantly higher than that in the other groups (p<0.001). Similarly, the rate of admission to the neonatal intensive care unit was significantly higher in the severe ICP group than in the other groups (p<0.001). According to Pearson correlation analyses, maternal serum bile-acid levels were positively correlated with TTN (r=0.082; p=0.002). Severe ICP, but not mild ICP, and serum bile-acid levels were positively correlated with increased TTN risk and reduced pulmonary surfactant levels.

A Case Report of Severe Intrahepatic Cholestasis of Pregnancy with Severe Liver Damage as the Main Manifestation

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during pregnancy [1]. Among these patients, bile cannot flow from the liver. The frequency of ICP varies widely between 0.1% and 25% with the specificity of ethnicity and geographic location. More cases about 0.8-1.46% were discovered in South Asian. The greatest prevalence was discovered in South American populations with up to 25% in women of Araucanian Indian. In China, the incidence has been reported be 0.8%-12%. ICP often appears in the late second or third trimester of pregnancy. It is a reversible form of cholestasis and tends to dissolve quickly after birth. Its characters involve pruritus, elevated serum bile acid levels, and abnormal liver function. It has been associated with sudden fetal death and fetal distress, stillbirth, and respiratory distress syndrome of newborn.

Genetic Disorders of Bile Acid Transport.

Genetic Disorders of Bile Acid Transport.

SERUM BILE ACIDS LEVEL IN CASES OF MECONIUM STAINED LIQUOR IN ELECTIVE CESAREAN SECTIONS AT EL-SHATBY MATERNITY UNIVERSITY HOSPITAL

Hepatic disorders of pregnancy comprise an impressive list of diseases and complications. Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, is considered the most common pregnancy-related liver disease. It takes place in the second or third trimester of gestation and it spontaneously disappears after delivery.The condition of asymptomatic hypercholanemia of pregnancy (AHP) has recently been reported. AHP is defined as increased serum bile acids in pregnancy in the absence of symptoms and other biochemical markers of ICP or any other hepatobiliary disease.The prevalence of this condition usually increases with gestational ageBile acids can pose a highly significant risk for the fetus resulting in several adverse perinatal outcomes such as meconium stained amniotic fluid (MSAF), prematurity, fetal distress and stillbirth. In ICP, MSAF has been reported in 16%-58% of all cases and up to 100% of cases affected by intrauterine death. It has been found that the risk of MSAF is associated not only with the magnitude of hypercholanemia at diagnosis but also with the early gestational onset of raised maternal serum bile acids. The frequency of MSAF is greater in pregnancies with higher reported levels of maternal serum bile acids.

TGR5 protects against cholestatic liver disease via suppressing the NF-κB pathway and activating the Nrf2/HO-1 pathway.

BackgroundCharacterized by the presence of inflammation, fibrosis, and bile duct proliferation, cholestatic liver disease (CLD) affects people of all age groups. Takeda G-protein-coupled receptor (TGR5) has been implicated in the suppression of inflammation via toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB). Kupffer cells and their M1 polarization play important roles in inflammation and cholestatic liver injury via production of pro-inflammatory cytokines. Nevertheless, the function of TGR5 signaling in CLD is largely unknown.MethodsWe conducted liver tissue experiments, animal experiments, serum marker testing, liver histology analysis, Kupffer cell experiments, RNA extraction and Real-time PCR, western blotting, evaluation of ROS production by flow cytometry and statistical differences were analyzed by student t-test using GraphPad Prism.ResultsWe found that serum bile acid (BA) and TGR5 levels were elevated in patients with cholestasis cirrhosis. Knockout of TGR5 in animals significantly increased bile duct ligation (BDL)-caused liver injury through increasing oxidative stress, promoting M1-predominant polarization of Kupffer cells, and elevating the serum levels of inflammatory cytokines. In contrast, TGR5 activation inhibited ROS production, secretion of pro-inflammatory cytokines, and M1-predominant polarization of Kupffer cells. Moreover, results showed that TGR5 exerted its effects via suppressing NF-κB signaling and activating nuclear factor 2 (Nrf2)/HO-1 signaling. Finally, the effect of TGR5 on cholestatic liver damage was also confirmed in vivo.ConclusionsTGR5 activation protected against BDL-induced CLD by both suppressing inflammation via inhibiting the NF-κB pathway and reducing ROS production via activation of Nrf2/HO-1 signaling. These findings show the importance of TGR5 in CLD and provide new insight into therapeutic strategies for CLD.

Effects of odevixibat on pruritus and bile acids in children with cholestatic liver disease: Phase 2 study

PurposeIleal bile acid transporter inhibition is a novel therapeutic concept for cholestatic pruritus and cholestatic liver disease progression. Odevixibat, a potent, selective, reversible ileal bile acid transporter inhibitor, decreases enteric bile acid reuptake with minimal systemic exposure. Oral odevixibat safety, tolerability, and efficacy in pediatric patients with cholestatic liver disease and pruritus were evaluated. Patients and methodsIn this phase 2, open-label, multicenter study, children received 10‒200 μg/kg oral odevixibat daily for 4 weeks. Changes in serum bile acid levels (primary efficacy endpoint), pruritus, and sleep disturbance were explored. ResultsTwenty patients were enrolled (8 females; 1‒17 years; 4 re-entered at a different dose). Diagnoses included progressive familial intrahepatic cholestasis (n = 13; 3 re-entries), Alagille syndrome (n = 6), biliary atresia (n = 3), and other intrahepatic cholestasis causes (n = 2; 1 re-entry). Mean baseline serum bile acid levels were high (235 µmol/L; range, 26‒564) and were reduced in the majority (−123.1 μmol/L; range, −394 to 14.5, reflecting reductions of up to 98%). Patient-reported diary data documented improved pruritus (3 scales) and sleep. With 100 μg/kg, mean (SEM) decrease was 2.8 (1.1) points for pruritus (visual analogue itch scale 0−10) and 2.9 (0.9) points for sleep disturbance (Patient-Oriented Scoring Atopic Dermatitis scale 0−10). Reduced pruritus correlated significantly with reduced serum bile acids (P ≤ 0.007). Significant correlations were also observed between autotaxin levels and pruritus. All patients completed the study. No serious adverse events were treatment related; most adverse events, including increased transaminases, were transient. ConclusionsOrally administered odevixibat was well tolerated, reduced serum bile acids, and improved pruritus and sleep disturbance in children with cholestatic diseases.

Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy (ICP), Versus Pregnant and Nonpregnant Controls in Asian Indian Women and a Proposed Scoring to Optimize Management in ICP.

This prospective clinical trial was conducted to assess serum bile acids (BA) levels in women with intrahepatic cholestasis of pregnancy (ICP) compared to both pregnant and non-pregnant controls; and evaluate perinatal outcome in relation to bile acid levels. A scoring is proposed based on biochemical markers to optimize management in ICP cases. Serum bile-acids(BA) were assessed in 71 intrahepatic-cholestasis of pregnancy(ICP) cases (group-I), versus 50 pregnant (group-II) and 35 non-pregnant (group-III) controls. Ursodeoxycholic acid (UDCA) was administered in ICP group. Baseline bilirubin (SB), aminotransferases (AT), alkaline-phosphatase were sent in groups I & II. Investigations were repeated in group-I after 4weeks. Perinatal complications were noted. Mean BA in group-I was 75.92 ± 39.9µmol/L which reduced to 41.3 ± 15.4µmol/L(45.6%, p < 0.001) with UDCA. Mean BA was 29.2 ± 5.7 and 5.9 ± 1.8µmol/L in group-II and group-III. UDCA significantly reduced itching-score. Rate of fetal distress linearly increased with the increasing baseline levels of serum BA, AT and SB: from 2.5 to 100% at BA < 40 and ≥ 200µmol/L, (p = 0.008); from 16.1 to 100% at AT < 100 and ≥ 500IU/mL(p = 0.016); and from 6.8 to 100% at SB < 0.8 and > 5mg/dL (p = 0.001); respectively. Their baseline levels were divided into 5 groups in correlation to fetal distress. Serum BA < 40, 40-80, 80-120, 120-200, ≥ 200µmol/L; AT < 100,100-200,200-500, ≥ 500IU/mL; and SB < 0.8, 0.8-1.0, 1.1-2, 2.1-5 and > 5mg/dL. Nutan ICP scoring was proposed with a score 0 to 4 given to each parameter and score-based management protocol was suggested for fetal surveillance and delivery. SBA are higher in Asian Indian pregnant women. Levels > 30µmol/L can be taken as a cut off for diagnosing ICP in Asian-Indian women. Adopting higher cut-offs for this geographic part will avoid over-diagnosing ICP and iatrogenic early termination of pregnancy. Suggested scoring will help clinicians in optimizing the time of delivery on an individualized basis.

Evaluation of the role of bile acids and serotonin as markers of pruritus in children with chronic cholestatic liver disease

Background and study aimsPruritus is an annoying symptom with an unclear pathogenesis accompanied by chronic cholestasis. This cross-sectional study was conducted to define the relationship between serum levels of presumed pruritogens (bile acids (BAs) and serotonin) and severity of pruritus in pediatric patients with chronic cholestatic liver disease. Patients and methodsA total of 28 children suffering from pruritus due to chronic cholestatic liver disease and 29 age- and sex-matched healthy control subjects were examined. Scores obtained used the 5-D itch scale were evaluated among patients. Serum levels of BAs and serotonin were determined using enzymatic assays and high-performance liquid chromatography, respectively. ResultsPatients had higher serum BA levels and lower serotonin levels than control subjects. Serum BA levels were significantly elevated in 61% of patients. The 5-D itch scale scores were significantly higher in cholestatic individuals with normal γ-glutamyl transpeptidase levels. Neither BA nor serotonin levels correlated with the severity of the 5-Ditch scale score. ConclusionNeither BA nor serotonin levels correlated with the severity of pruritus, indicating that they may not be good laboratory markers for the intensity of itch in children with cholestasis. Our findings suggest that it is necessary to identify another potential pruritogenic mediator, most probably of a biliary origin.

Prenatal ethanol exposure increases maternal bile acids through placental transport pathway

High maternal serum bile acid level is common and sometimes harmful to the gravida. This study aimed to confirm the bile acid phenotypic change caused by prenatal ethanol exposure (PEE) and elucidate its placental mechanism. Pregnant Wistar rats were administered intragastrically with ethanol 4 g/kg⋅d from gestational day 9–20. Total bile acids (TBA) were detected in maternal, fetal serum and placental tissues, increasing significantly in the serum but no significant change in the placental tissues. Meta-analysis was performed and verified the efficacy of the PEE-induced model based on published data from several relevant studies. Mining of microarray data from human and rat placental sources identified the involvement of bile acid metabolism and its significant genes, which were verified by RT-qPCR and western blotting on tissues and treated BeWo cells with the administration of FXR/PXR siRNAs or FXR/PXR agonists. Our examination, consistent with microarray data and wet experiments, showed that organic anion transporter polypeptide-related protein 2B1 (Oatp2b1), multidrug resistance-associated proteins 3 (Mrp3) and breast cancer resistance protein (Bcrp) expression were increased, while nuclear receptor farnesoid X receptor (Fxr) was decreased but pregnane X receptor (Pxr) was increased. Furthermore, the interventional experiments confirmed that FXR regulated Bcrp while PXR regulated Oatp2b1 and Mrp3. In summary, PEE could induce high bile acid level in maternal serum and its mechanism is associated with the high expression of BCRP/MRP3/OATP2B1 in the placenta through up-regulating PXR and down-regulating FXR, thereby leading to an excessive bile acid transport to maternal blood via the placenta. Our study provides a novel perspective in terms of placenta, explaining the increased maternal blood bile acids under the toxicity of PEE.

Association between Pre-Diagnostic Serum Bile Acids and Hepatocellular Carcinoma: The Singapore Chinese Health Study.

Simple SummaryHepatocellular carcinoma (HCC) is a common cancer with poor prognosis. The increasing incidence rate of HCC in developed countries has been linked to increasing prevalence of metabolic dysfunction-associated fatty liver disease, which has characteristics of altered bile acid metabolism that may predate hepatocarcinogenesis. The aim of the present study was to assess the association of circulating bile acid levels in pre-diagnostic serum with the risk of developing HCC in a general population in Singapore. Primary conjugated bile acids were most strongly associated with increased risk of HCC whereas the ratios of secondary over primary bile acids were significantly associated with reduced risk. These results support a contributing role of dysmetabolism of bile acids in the development of HCC. The modulation of bile acid metabolism through alteration of gut microbiota may be an effective strategy for primary prevention against HCC in individuals with metabolic dysfunction-associated fatty liver disease.Hepatocellular carcinoma (HCC) is a commonly diagnosed malignancy with poor prognosis. Rising incidence of HCC may be due to rising prevalence of metabolic dysfunction-associated fatty liver disease, where altered bile acid metabolism may be implicated in HCC development. Thirty-five bile acids were quantified using ultra-performance liquid chromatography triple-quadrupole mass spectrometry assays in pre-diagnostic serum of 100 HCC cases and 100 matched controls from the Singapore Chinese Health Study. Conditional logistic regression was used to assess associations for bile acid levels with risk of HCC. Conjugated primary bile acids were significantly elevated whereas the ratios of secondary bile acids over primary bile acids were significantly lower in HCC cases than controls. The respective odds ratios and 95% confidence intervals of HCC were 6.09 (1.75–21.21) for highest vs. lowest tertile of cholic acid species and 30.11 (5.88–154.31) for chenodeoxycholic acid species. Doubling ratio of taurine-over glycine-conjugated chenodeoxycholic acid was associated significantly with 40% increased risk of HCC whereas doubling ratio of secondary over primary bile acid species was associated with 30–40% reduced risk of HCC. In conclusion, elevated primary bile acids and taurine over glycine-conjugated ratios were strongly associated with HCC risk whereas the ratios of secondary bile acids over primary bile acids were inversely associated with HCC risk.

Serum Bile Acid Profiles Improve Clinical Prediction of Nonalcoholic Fatty Liver in T2DM patients.

Background: The present study aimed to assess the ability of serum bile acid profiles to predict the development of nonalcoholic fatty liver (NAFL) in type 2 diabetes mellitus (T2DM) patients. Methods: Using targeted ultraperformance liquid chromatography (UPLC) coupled with triple quadrupole mass spectrometry (TQ/MS), we compared serum bile acid levels in T2DM patients with NAFL (n = 30) and age- and sex-matched T2DM patients without NAFL (n = 36) at the first time. Second, an independent cohort study of T2DM patients with NAFL (n = 17) and age- and sex-matched T2DM patients without NAFL (n = 20) was used to validate the results. The incremental benefits of serum biomarkers, clinical variables alone, or with biomarkers were then evaluated using receiver operating characteristic (ROC) curves and decision curve analysis. The area under the curve (AUC), integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used to evaluate the biomarker predictive abilities. Results: The serum bile acid profiles in T2DM patients with NAFL were significantly different from T2DM patients without NAFL, as characterized by the significant elevation of LCA, TLCA, TUDCA, CDCA-24G, and TCDCA, which may be potential biomarkers for the identification of NAFL in T2DM patients. Based on the improvement in AUC, IDI, and NRI, the addition of 5 bile acids to a model with clinical variables statistically improved its predictive value. Similar results were found in the validation cohort. Conclusions: These results highlight that the detected biomarkers may contribute to the progression of NAFL in T2DM patients, and these biomarkers particularly in combination may help in the diagnosis of NAFL and allow earlier intervention in T2DM patients.

IFT-A deficiency in juvenile mice impairs biliary development and exacerbates ADPKD liver disease.

Polycystic liver disease (PLD) is characterized by the growth of numerous biliary cysts and presents in patients with autosomal dominant polycystic kidney disease (ADPKD), causing significant morbidity. Interestingly, deletion of intraflagellar transport-B (IFT-B) complex genes in adult mouse models of ADPKD attenuates the severity of PKD and PLD. Here we examine the role of deletion of an IFT-A gene, Thm1, in PLD of juvenile and adult Pkd2 conditional knockout mice. Perinatal deletion of Thm1 resulted in disorganized and expanded biliary regions, biliary fibrosis, increased serum bile acids, and a shortened primary cilium on cytokeratin 19+ (CK19+) epithelial cells. In contrast, perinatal deletion of Pkd2 caused PLD, with multiple CK19+ epithelial cell-lined cysts, fibrosis, lengthened primary cilia, and increased Notch and ERK signaling. Perinatal deletion of Thm1 in Pkd2 conditional knockout mice increased hepatomegaly, liver necrosis, as well as serum bilirubin and bile acid levels, indicating enhanced liver disease severity. In contrast to effects in the developing liver, deletion of Thm1 alone in adult mice did not cause a biliary phenotype. Combined deletion of Pkd2 and Thm1 caused variable hepatic cystogenesis at 4 months of age, but differences in hepatic cystogenesis between Pkd2- and Pkd2;Thm1 knockout mice were not observed by 6 months of age. Similar to juvenile PLD, Notch and ERK signaling were increased in adult Pkd2 conditional knockout cyst-lining epithelial cells. Taken together, Thm1 is required for biliary tract development, and proper biliary development restricts PLD severity. Unlike IFT-B genes, Thm1 does not markedly attenuate hepatic cystogenesis, suggesting differences in regulation of signaling and cystogenic processes in the liver by IFT-B and -A. Notably, increased Notch signaling in cyst-lining epithelial cells may indicate that aberrant activation of this pathway promotes hepatic cystogenesis, presenting as a novel potential therapeutic target. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Colestasis intrahepática del embarazo. Un reto más para la obstetricia

Intrahepatic cholestasis of pregnancy, is the most common specific liver disorder during pregnancy, it is a multifactorial condition that appears in genetically susceptible women and, it is mainly characterized by palmoplantar itching predominantly at night. Its importance lies in the considerable fetal morbidity and mortality. Although the treatment is simple, we must know how to make the diagnosis. Objective: To carry out an updated and detailed review of the national and international bibliography of etiology, diagnostic tests, treatment, perinatal results, and their association with other pregnancy pathologies. Methodology: A search of the literature published in English and Spanish was conducted in databases such as PubMed / MEDLINE, Ovid, MD Consult, and others, using the keywords: intrahepatic cholestasis of pregnancy, etiology, diagnosis, treatment, perinatal adverse effects, preeclampsia, tween pregnancy. articles were selected from the obtained, which were classified and used as support to carry out this review. Results: An update regarding the diagnosis and treatment of this disease is provided, to act as a clinical guide for healthcare professionals. Conclusion: This disease is an important entity to diagnose in order to avoid the fetal adverse effects that implies., tThe main limitation is the lack of determination of serum bile acid levels in our country, therefore, clinical suspicion becomes the most useful tool for diagnosis and early treatment. Keywords: Intrahepatic cholestasis; pregnancy; bile acids; perinatal adverse outcomes.

A model based on routine liver tests can reliably exclude intrahepatic cholestasis of pregnancy

ObjectivesSerum bile acid (BA) levels testing is used for the diagnosis of intrahepatic cholestasis of pregnancy (ICP). We aimed to determine the performance of routine liver tests in the evaluation of ICP. MethodsA retrospective cohort study conducted at a university hospital, including all pregnant women who underwent serum BA levels testing due to suspected ICP during 2007–2019. Liver tests were performed in all women including: aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALK), gamma-glutamyl transferase (GGT), and total bilirubin (TB). The optimal combination of laboratory values was determined by an algorithm developed in the Python programming language. ResultsOf 640 women who met the inclusion criteria, 22% (n = 142) were diagnosed with ICP (serum BA>10 μmol/L). A combined laboratory score of: (TB>11 μmol/L) or (ALK>255 U/L) or (GGT>32 U/L) or (AST>31 U/L), had a sensitivity of 94%, negative predictive value (NPV) of 97%, specificity of 50%, positive predictive value of 35%, and a negative likelihood ratio of 0.11 for the diagnosis of ICP. The AUC of the laboratory model alone was 0.72 (95% CI: 0.69–0.75). The addition of history of ICP to the suggested laboratory score resulted in a sensitivity of 97%, NPV of 98% and a negative likelihood ratio of 0.06. The AUC of the final model was 0.76 (95% CI: 0.72–0.79). ConclusionsA combined laboratory score incorporating AST, GGT, ALK and TB was shown to reliably exclude the diagnosis of ICP. This may be particularly useful in settings with limited access to BA levels testing.

Serum bile acid levels assist the prediction of biliary stricture and survival after liver transplantation in children.

Biliary stricture is an important biliary complication after liver transplant in children. We aimed to investigate the utility of serum bile acid levels for prediction of biliary stricture in children after liver transplant. This study enrolled 60 children who underwent liver transplantation at a mean age of 2.04±0.30 years; serum bile acid levels were surveyed in a cross-sectional design. These patients were followed regularly at our institute, and the clinical data were collected prospectively. The major indication of liver transplant in this pediatric cohort was biliary atresia (78.33%). During the follow-up period (3.08±0.30 years), nine patients (15%) developed biliary stricture after the check of serum bile acid. A receiver operating characteristic curve analysis yielded a serum bile acid cutoff of >40 μM for the prediction of biliary stricture (P = 0.002). A serum bile acid level >40 is the most important predictor of a biliary stricture after liver transplant (odds ratio=65.65, P = 0.003) after adjusting for gender and GGT levels. The phenomenon remained on Cox's proportional hazard survival analysis (hazard ratio =15.42, P = 0.001). The mortality risk after liver transplant was significantly higher in subjects with serum bile acid levels >40 μM than in those with levels ≤40 μM (log-rank test, P = 0.004).Conclusion: Serum bile acid levels can be used for non-invasive screening and prediction of biliary stricture and mortality in children after liver transplantation. What is Known: • Biliary stricture is a major biliary complication after pediatric liver transplantation, and we showed the serum bile acid level significantly associates with biliary stricture. What is New: • In this study, we demonstrated the serum bile acid level may assist in the early detection of biliary stricture and mortality non-invasively.