Association of ABCB4 and ABCB11 nucleotide variants with intrahepatic cholestasis of pregnancy

2019 ◽  
Vol 88 (4) ◽  
pp. 209-217
Author(s):  
Milena Gruszczyńska-Losy ◽  
Adrianna Mostowska ◽  
Łukasz Adamczak ◽  
Paweł Jagodziński ◽  
Ewa Wender-Ożegowska ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Melting Curve ◽  
Liver Disorder ◽  
Melting Curve Analysis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during gestation. The exact pathogenesis of ICP is multifactorial and still unclear. Therefore, our study aimed to check whether the selected ABCB4and ABCB11nucleotide variants are associated with an increased risk of ICP. Methods:ICP was diagnosed based on clinical symptoms characteristic of this disease and confirmed by increase in serum bile acids and transaminases, spontaneous resolution of clinical symptoms and normalization of laboratory tests after delivery. The total of 86 pregnant women meeting the criteria were included into the study. Healthy pregnant women with uncomplicated pregnancy served as control group (n=310). Sixcommon nucleotide variants in theABCB11and ABCB4genes were genotypedwith the use of high-resolution melting curve analysis. Conclusion:Our study did not show any significant association of analysed ABCB4and ABCB11nucleotide variants with the increased risk of intrahepatic cholestasis of pregnancy.

scholarly journals Intrahepatic Cholestasis in Pregnancy: Review of the Literature

2020 ◽  
Vol 9 (5) ◽  
pp. 1361
Author(s):  
Joanna Piechota ◽  
Wojciech Jelski
Keyword(s):  
Intrahepatic Cholestasis ◽  
Clinical Symptoms ◽  
Clinical Signs ◽  
Serum Levels ◽  
Premature Delivery ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Perinatal Complications ◽  
Hepatic Disorder ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered.

scholarly journals Alpha-1 Antitrypsin Z Variant (AAT PI*Z) as a Risk Factor for Intrahepatic Cholestasis of Pregnancy

2021 ◽  
Vol 12 ◽  
Author(s):  
Przemyslaw Kosinski ◽  
Malgorzata Kedzia ◽  
Adrianna Mostowska ◽  
Pawel Gutaj ◽  
Michal Lipa ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Fetal Monitoring ◽  
Fold Increase ◽  
Liver Disorder ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Increased Risk ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin ◽  
Cholestasis Of Pregnancy ◽  
In Pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP; prevalence 0.2–15.6%) is the most common pregnancy-related liver disorder. It may have serious consequences for a pregnancy, including increased risk of preterm delivery, meconium staining of amniotic fluid, fetal bradycardia, distress, and fetal demise. In cases of high bile acids (>100μmol/L), patients have 10-fold increase in the risk of stillbirth. Biophysical methods of fetal monitoring, such as cardiotocography, ultrasonography, or Doppler have been proven unreliable for risk prediction in the course of intrahepatic cholestasis. Therefore, we believe extensive research for more specific, especially early, markers should be carried out. By analogy with cholestasis in children with inherited alpha-1 antitrypsin deficiency (AATD), we hypothesized the SERPINA1 Z pathogenic variant might be related to a higher risk of cholestasis in pregnancy. This study aimed to investigate the most common AATD variants (Z and S SERPINA1 alleles) in a group of cholestatic pregnant women.Results: The Z carrier frequency was calculated to be 6.8%, which is much higher compared to the general population [2.3%; the Chi-squared test with Yates correction is 6.8774 (p=0.008)].Conclusion: Increased prevalence of SERPINA1 PI*Z variant in a group of women with intrahepatic cholestasis may suggest a possible genetic origin of a higher risk of intrahepatic cholestasis in pregnancy.

scholarly journals Administration of Sex Hormone Preparations as a Risk Factor in the Development of Intrahepatic Cholestasis of Pregnancy and Biliary Sludge in Pregnant Women

2018 ◽  
Vol 28 (4) ◽  
pp. 55-65 ◽  
Author(s):  
Yu. B. Uspenskaya ◽  
I. V. Kuznetsova ◽  
A. A. Sheptulin ◽  
N. V. Goncharenko ◽  
A. N. Gerasimov ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Sex Hormones ◽  
Intrahepatic Cholestasis ◽  
Sex Hormone ◽  
Ultrasound Screening ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Art Programs ◽  
Biliary Sludge ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Sex hormone preparations are widely used in obstetrics for the treatment of infertility and miscarriage. Possible adverse effect of sex hormone preparations during pregnancy is their potential adverse impact on the hepatobiliary system. The most common pathology of the liver and gallbladder associated with pregnancy are intrahepatic cholestasis of pregnancy (ICP) and biliary sludge (BS).Aim.  The aim of the study is to evaluate the effect of female sex hormones on the course and effectiveness of treatment of ICP and BS during pregnancy. Materials and methods.  The study included 158 pregnant women (97 patients with ICP and 61 patients with BS). Exogenous hormonal effects were the use of assisted reproductive technologies (ARTs) and in vitro fertilization (IVF) for the onset of conception and/or the use of estrogen and progesterone preparations during pregnancy. ICP was diagnosed on the basis of detection of an elevated level of bile acids (above 8 μmol/L) in the blood serum. Patients underwent clinical, laboratory and instrumental studies (abdominal ultrasound, including the assessment of gallbladder motor-evacuator function initially and after 2 months of treatment, and pelvic ultrasound). Pruritus intensity associated with ICP was assessed using a 0–3 score scale. Patients with BS received treatment with ursodeoxycholic acid (UDCA) in a dose of 250–750 mg and choleretic herbal preparation (artichoke extract) for 2 months. Patients with ICP were treated with UDCA in a dose of 500–2000 mg until delivery. Biochemical laboratory parameters in the ICP group were evaluated after 1 and 2 weeks of treatment.Results.  More than half of patients with BS and ICP were taking sex hormone preparations or had a pregnancy that occurred after the application of ART programs. In patients who became pregnant after ART, the ICP developed at a significantly earlier time than in patients with a naturally occurring pregnancy (p < 0.001). The use of sex hormones proved to be interrelated with a high frequency of cholestasis recurrence after its regression in the course of the treatment (p < 0.001). Patients with pregnancy after ART programs, as well as taking sex hormones, had an increased risk of BS developement. The intake of sex hormones (p = 0.005) in patients with ICP was associated with a more frequent development of preeclampsia and the need for caesarean section (p = 0.003). The use of ART programs and hormonal therapy, as well as the presence of BS in patients with ICP, were interrelated with oxidative stress. BS on the ICP background was associated with the development of intrauterine fetal hypoxia. In pregnant women with BS, the reception of progestins was significantly (p = 0.004) correlated with functional impairment of the motor function of the biliary tract (BT). In the presence of BS, ICP occurs with more severe liver damage, and the patients are inferior to respond to UDCA treatment. Prognostic factors in the insufficient effectiveness of BS treatment: the use of sex hormone preparations during pregnancy, the presence of the polycystic ovary syndrome (PCOS) in the anamnesis, an older age at the time of pregnancy and conception after ART.Conclusion.The use of sex hormone preparations and ART programs are shown to be additional factors contributing to the emergence of ICP and BS during pregnancy. For the pregnant women taking sex hormone preparations and/or becoming pregnant after ART programs, it is important to conduct laboratory and ultrasound screening for early detection and timely treatment of ICP and BS. BC patients of older ages who have become pregnant after ART programs and take sex hormones preparations and/or have a PCOS in an anamnesis may need longer or repeated courses of BS treatment. 

scholarly journals The relationship of bile acid with biochemical tests in the diagnosis of intrahepatic cholestasis of pregnancy

2021 ◽  
Vol 38 (4) ◽  
pp. 485-489
Author(s):  
Cuma TAŞIN ◽  
Revan Sabri ÇİFTÇİ
Keyword(s):  
Bile Acid ◽  
Preterm Delivery ◽  
Sensitivity And Specificity ◽  
Intrahepatic Cholestasis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Biochemical Tests ◽  
Increased Risk ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

Intrahepatic pregnancy cholestasis (ICP) is associated with increased fetal complications. It is linked to an increased risk. Early diagnosis of this disease reduces these fetal complications. In this study, it was aimed to determine the sensitivity and specificity of biochemical tests according to cut off values. The values of 14 patients with bile acid ≥40 μmol / L diagnosed with intrahepatic cholestasis of pregnancy and 40 patients with bile acid <40 μmol / L were compared retrospectively with 60 control patients. In ICP patients, the ALT and AST values in patients with group 1 with bile acid ≥40 μmol / L and group 2 with bile acid <40 μmol / L were significantly higher than the control group (p = 0.0001 for both markers). Groups 1 and 2 with ICP patients have high sensitivity and specificity compared to the cut off value of ALT and AST. In our study, it was found that increased the risk of preterm delivery in ICP patients. Especially in cases where bile acid was ≥ 40 μmol / L, complications such as preterm delivery and low birth weight increased in proportion to the increase in bile acid. In the ICP patients, AST and especially ALT values increased in proportion to the increase in bile acid.

Assessment of Mechanical Fetal PR Interval in Intrahepatic Cholestasis of Pregnancy and Its Relationship with the Severity of the Disease

2019 ◽  
Vol 37 (14) ◽  
pp. 1476-1481
Author(s):  
Kadriye Yakut ◽  
Fatma Doğa Öcal ◽  
Merve Öztürk ◽  
Filiz Halici Öztürk ◽  
Yüksel Oğuz ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Control Group ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Positive Correlation ◽  
Severity Of Disease ◽  
Pr Interval ◽  
Fetal Complications ◽  
Severity Of The Disease ◽  
Cholestasis Of Pregnancy

Abstract Objective This study aimed to investigate the fetal atrioventricular conduction system in intrahepatic cholestasis of pregnancy (ICP) by measuring the fetal mechanical PR interval and to explore the significance of predicting the severity of the disease. Study Design Forty pregnant women diagnosed with ICP, classified as severe and mild, and 40 healthy pregnant women participated in the study. Fetal mechanical PR interval was calculated, and fetal mechanical PR interval and neonatal outcome were compared between the groups. The relationship between the mechanical PR interval and the severity of ICP was analyzed. Results The fetal mechanical PR interval was significantly longer in the ICP group than in the control group (p < 0.005). Likewise, laboratory parameters such as transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) and total bilirubin levels were significantly higher in the ICP group (p < 0.005).There were no statistically significant differences in the fetal complications. There was a positive correlation between the severity of disease and fetal PR interval. Conclusion A prolonged fetal mechanical PR interval in fetuses of mothers with ICP was demonstrated in this study. It was also shown that there was a positive correlation between fetal PR interval and severity of the disease. The study concluded that fetal mechanical PR interval measurement can be used to predict the severity of disease in ICP.

scholarly journals A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
William M. Hague ◽  
Leonie Callaway ◽  
Jennifer Chambers ◽  
Lucy Chappell ◽  
Suzette Coat ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Ursodeoxycholic Acid ◽  
Intrahepatic Cholestasis ◽  
Early Onset ◽  
Randomised Trial ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Spontaneous Preterm Birth ◽  
Open Label ◽  
Increased Risk ◽  
Cholestasis Of Pregnancy

Abstract Background Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. Methods We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. Discussion Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing “standard” UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. Trial identifiers Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018–004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

scholarly journals Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Rong Li ◽  
Xuehai Chen ◽  
Zhongzhen Liu ◽  
Yan Chen ◽  
Chuan Liu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Premature Delivery ◽  
Clinical Parameters ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Control Groups ◽  
And Control ◽  
Cholestasis Of Pregnancy

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease. Methods A total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified. Results Elevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray–Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups. Conclusions Our research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.

scholarly journals Comparative Proteomics Analysis of Placenta from Pregnant Women with Intrahepatic Cholestasis of Pregnancy

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e83281 ◽  
Author(s):  
Ting Zhang ◽  
Yueshuai Guo ◽  
Xuejiang Guo ◽  
Tao Zhou ◽  
Daozhen Chen ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Intrahepatic Cholestasis ◽  
Comparative Proteomics ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Proteomics Analysis ◽  
Cholestasis Of Pregnancy

Fetal complications due to intrahepatic cholestasis of pregnancy

2015 ◽  
Vol 43 (2) ◽  
Author(s):  
Patrik Šimják ◽  
Antonín Pařízek ◽  
Libor Vítek ◽  
Andrej Černý ◽  
Karolína Adamcová ◽  
...  
Keyword(s):  
Intrahepatic Cholestasis ◽  
Current Knowledge ◽  
Elevated Serum ◽  
Liver Function Tests ◽  
Liver Disorder ◽  
Intrauterine Fetal Death ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Management Options ◽  
Fetal Complications ◽  
Cholestasis Of Pregnancy

AbstractIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.

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