Diagnostic and therapeutic profiles of serum bile acids in women with intrahepatic cholestasis of pregnancy-a pseudo-targeted metabolomics study

Cui, Yue; Xu, Bo; Zhang, Xiaoqing; He, Yifan; Shao, Yina; Ding, Min

doi:10.1016/j.cca.2018.04.035

Cited by 46 publications

(49 citation statements)

References 25 publications

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“…Cui et al 37 Furrer et al 24 Kowalska-Kańka et al 38 Zhang et al 26 Ataalla et al 36 15 countries, from five continents, were included in the aggregate data meta-analysis, whereas IPD data were available from 14 countries, from five continents.…”

Section: Subtotalmentioning

confidence: 99%

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-Analyses

Ovadia¹,

Seed²,

Sklavounos³

et al. 2020

Obstetric Anesthesia Digest

121

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Background Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth. Methods We did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and populationbased studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134. Findings We assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0•91%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0•32%) of 163 947 control pregnancies (odds ratio [OR] 1•46 [95% CI 0•73-2•89]; I²=59•8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0•83 [95% CI 0•74-0•92]), but not alanine aminotransferase (ROC AUC 0•46 [0•35-0•57]). For singleton pregnancies, the prevalence of stillbirth was three (0•13%; 95% CI 0•02-0•38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 µmol/L versus four (0•28%; 0•08-0•72) of 1412 cases with total bile acids of 40-99 µ...

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Section: Subtotalmentioning

confidence: 99%

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-Analyses

Ovadia¹,

Seed²,

Sklavounos³

et al. 2020

Obstetric Anesthesia Digest

121

View full text Add to dashboard Cite

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“…In a serum targeted metabolomics ICP study, 60 BAs were detected of which most conjugated BAs were elevated in ICP. Metabolomics was also employed to monitor BAs during treatment with ursodeoxycholic acid [108]. Targeted metabolomics of urinary sulfated BAs was used to define biomarkers for the diagnosis and grading of ICP.…”

Section: Cholestasismentioning

confidence: 99%

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Beyoğlu

Idle

2020

Metabolites

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In recent years, there has been a plethora of attempts to discover biomarkers that are more reliable than α-fetoprotein for the early prediction and prognosis of hepatocellular carcinoma (HCC). Efforts have involved such fields as genomics, transcriptomics, epigenetics, microRNA, exosomes, proteomics, glycoproteomics, and metabolomics. HCC arises against a background of inflammation, steatosis, and cirrhosis, due mainly to hepatic insults caused by alcohol abuse, hepatitis B and C virus infection, adiposity, and diabetes. Metabolomics offers an opportunity, without recourse to liver biopsy, to discover biomarkers for premalignant liver disease, thereby alerting the potential of impending HCC. We have reviewed metabolomic studies in alcoholic liver disease (ALD), cholestasis, fibrosis, cirrhosis, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Specificity was our major criterion in proposing clinical evaluation of indole-3-lactic acid, phenyllactic acid, N-lauroylglycine, decatrienoate, N-acetyltaurine for ALD, urinary sulfated bile acids for cholestasis, cervonoyl ethanolamide for fibrosis, 16α-hydroxyestrone for cirrhosis, and the pattern of acyl carnitines for NAFL and NASH. These examples derive from a large body of published metabolomic observations in various liver diseases in adults, adolescents, and children, together with animal models. Many other options have been tabulated. Metabolomic biomarkers for premalignant liver disease may help reduce the incidence of HCC.

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“…Clinical assays for detecting bile acid profiles might be feasible non-invasive biomarkers [9]. Several studies have reported altered serum bile acid profiles, including intrahepatic cholestasis in pregnancy, [10] nonalcoholic fatty liver disease, [11] and neonatal intrahepatic cholestasis caused by citrin deficiency [12]. It was proposed that different types of serum bile acids could be found in circumstances where enterohepatic circulation of bile acids is obstructed.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of bile acid profile-based scoring system for identification of biliary atresia: a prospective study

et al. 2020

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Background: Early distinguishing biliary atresia from other causes of infantile cholestasis remains a major challenge. We aimed to develop and validate a scoring system based on bile acid for identification of biliary atresia. Methods: In a prospective study, a total of 141 infants with cholestasis were enrolled in two sets (derivation cohort, n = 66; validation cohort, n = 75) from 2014 to 2018. Variables with significant difference between biliary atresia and non-biliary atresia infants were selected in the derivation cohort. Then, a scoring system including those variables was designed and validated. Results: Among 66 patients in the derivation cohort, 34 (51.5%) had biliary atresia. A scoring system was proposed with the following variables: glycochenodeoxycholic acid/chenodeoxycholic acid, clay stool, and gamma-glutamyl transferase. The total score ranged from 0 to 41, and a cutoff value of 15 identified biliary atresia with an area under receiver operating characteristic curve of 0.87 (95% confidence interval, 0.77-0.94), sensitivity of 85.3%, and specificity of 81.3% in the derivation cohort; these values were also confirmed in a validation cohort with a sensitivity of 90.0% and specificity of 80.0%. Conclusions: The proposed simple scoring system had good diagnostic accuracy for estimating the risk of biliary atresia in infants with cholestasis.

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Diagnostic and therapeutic profiles of serum bile acids in women with intrahepatic cholestasis of pregnancy-a pseudo-targeted metabolomics study

Cited by 46 publications

References 25 publications

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-Analyses

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-Analyses

Metabolomic and Lipidomic Biomarkers for Premalignant Liver Disease Diagnosis and Therapy

Development and validation of bile acid profile-based scoring system for identification of biliary atresia: a prospective study

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