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.

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 Obstetric Cholestasis: A Review and Update

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Olawumi Adaramodu ◽  
Anthony Kodzo-Grey Venyo
Keyword(s):  
Liver Function ◽  
Bile Acids ◽  
Intrahepatic Cholestasis ◽  
Liver Function Tests ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Third Trimester ◽  
Serum Bile Acids ◽  
Function Tests ◽  
Cholestasis Of Pregnancy ◽  
In Pregnancy

Obstetric cholestasis (OC) is a liver disorder that occurs in the late second and early third trimester of pregnancy characterized by pruritus with increased serum bile acids and other liver function tests. The pathophysiology of OC is still not completely understood. The symptoms and biochemical abnormality rapidly resolve after delivery. OC is associated with an increased risk of adverse obstetrical outcomes. The aetiology of obstetric cholestasis of pregnancy is poorly understood and is thought to be complicated and multifactorial.  OC typically occurs in the late second trimester when the oestrogen levels are the highest in pregnancy. The most common complaint is generalized intense pruritus, which usually starts after the 30th week of pregnancy. Pruritus can be more common in the palms and soles and is typically worse at night. Other symptoms of cholestasis, such as nausea, anorexia, fatigue, right upper quadrant pain, dark urine, and pale stool, can be present. Clinical jaundice is rare but may present in 14% to 25% of patients after 1 to 4 weeks of the onset of pruritus. Some patients also complain of insomnia as a result of pruritus. Generally, physical examination is unremarkable except for scratch marks on the skin from pruritus. Pruritus is a cardinal symptom of intra-hepatic cholestasis of pregnancy (ICP) and may precede biochemical abnormalities. The diagnosis of intrahepatic cholestasis of pregnancy is via the presence of clinical symptoms pruritus in the third trimester with elevated maternal total serum bile acids and excluding other diagnoses, which can cause similar symptoms and lab abnormalities. Fasting blood samples should be used to check for the total bile salt acid level as it can become elevated in the postprandial state. Once the diagnosis of OC of pregnancy is confirmed, immediate treatment is necessary, and the primary goal of therapy is to decrease the risk of perinatal morbidity and mortality and to alleviate maternal symptoms. Maternal pruritus can be alleviated with use of moisturisers and oral antihistamines. Ursodeoxycholic acid (UDCA) is the drug of choice for the treatment of ICP. Many authors have advocated elective early delivery of women with intrahepatic cholestasis of pregnancy to reduce the risk of sudden foetal death. The Royal College of Obstetricians and Gynaecologists recommends induction of labour after 37+0 weeks of gestation. Obstetric cholestasis of pregnancy is not an indication for Caesarean delivery. Postpartum pruritus typically disappears in the first 2 to 3 days following delivery, and serum bile acid concentrations will normalize eventually. ICP is not a contraindication to breastfeeding, and mothers with a history of ICP in pregnancy can breastfeed their infants. Postpartum monitoring and follow up of bile acids and liver function tests should be done in 4-6 weeks to ensure resolution. Women with the persistent abnormality of liver function test after 6 to 8 weeks require investigation for other aetiologies.

The skin in pregnancy

2010 ◽  
pp. 2149-2153
Author(s):  
Fenella Wojnarowska
Keyword(s):  
Pregnant Woman ◽  
Intrahepatic Cholestasis ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Cholestasis Of Pregnancy ◽  
In Pregnancy

Pregnancy dermatoses are common, and because they are usually very itchy may ruin the life of the pregnant woman. It is particularly important to recognize when itch is due to intrahepatic cholestasis of pregnancy, which has important implications for the health of both mother and fetus (see ...

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.

Resveratrol reduces matrix metalloproteinases and alleviates intrahepatic cholestasis of pregnancy in rats

2016 ◽  
Vol 94 (4) ◽  
pp. 402-407 ◽  
Author(s):  
Zhong Chen ◽  
Lingqing Hu ◽  
Mudan Lu ◽  
Zongji Shen
Keyword(s):  
Ursodeoxycholic Acid ◽  
Flow Rate ◽  
Intrahepatic Cholestasis ◽  
Bile Flow ◽  
Liver Disorder ◽  
Enzymatic Activities ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Resveratrol Treatment ◽  
Bile Flow Rate ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a severe liver disorder occurring specifically in pregnancy, and matrix metalloproteinase (MMP)-2 and MMP-9 were found to be elevated in ICP patients. Using ethinylestradiol-induced ICP rats as the model, we examined the effect of resveratrol on ICP symptoms such as bile flow rate, serum enzymatic activities, and TBA concentration, as well as MMP levels, and compared with the known ICP drug ursodeoxycholic acid. Both MMP-2 and MMP-9 were upregulated in ICP rats, and resveratrol treatment could inhibit the elevation of both MMPs, whereas ursodeoxycholic acid did not exhibit any effect. Although ursodeoxycholic acid alleviated ICP symptoms, resveratrol treatment in general exhibited better outcome in restoring bile flow rate, serum enzymatic activities, and TBA concentration. Our results for the first instance strongly supported the potential of RE as a new therapeutic agent in treating ICP, possibly through inhibiting MMP-2 and MMP-9.

scholarly journals Intrahepatic cholestasis of pregnancy

2021 ◽  
Vol 16 (S3) ◽  
pp. 50-55
Author(s):  
Ana Maria SCUTELNICU ◽  
◽  
Brînduşa Ana CIMPOCA-RAPTIS ◽  
Anca Marina CIOBANU ◽  
Nicolae GICĂ ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Intrahepatic Cholestasis ◽  
Perinatal Outcomes ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Fetal Asphyxia ◽  
Increased Risk ◽  
Adverse Perinatal Outcomes ◽  
Adverse Pregnancy ◽  
Cholestasis Of Pregnancy ◽  
Meconium Stained Amniotic Fluid

Intrahepatic cholestasis of pregnancy is the most common liver disease during pregnancy. The main features are maternal pruritus, in the absence of a rash, and raised serum bile acids. Intrahepatic cholestasis of pregnancy is associated with an increased risk of adverse perinatal outcomes, including preterm birth, meconium-stained amniotic fluid, fetal asphyxia with neonatal unit admission or even stillbirth. The main treatment option is ursodeoxycholic acid. We review the etiology, diagnosis, adverse pregnancy outcomes, focusing especially on management of this intriguing condition.

scholarly journals May Circulating Steroids Reveal a Predisposition to Intrahepatic Cholestasis of Pregnancy in Non-Pregnant Women?

2018 ◽  
pp. S499-S510
Author(s):  
P. ŠIMJÁK ◽  
M. HILL ◽  
A. PAŘÍZEK ◽  
L. VÍTEK ◽  
M. VELÍKOVÁ ◽  
...  
Keyword(s):  
Gestational Age ◽  
Intrahepatic Cholestasis ◽  
Liver Disorder ◽  
Maternal Blood ◽  
Gas Chromatography Mass Spectrometry ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Third Trimester ◽  
Umbilical Blood ◽  
Subject Factor ◽  
Cholestasis Of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5α/β-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.

scholarly journals Influence of severity of total bile acids and mode of delivery on the perinatal outcomes in intrahepatic cholestasis of pregnancy

2021 ◽  
Author(s):  
Chengcai Kong ◽  
Fenglin Mei ◽  
Pingping Xue ◽  
Jingyun Cao ◽  
Yong Li ◽  
...  
Keyword(s):  
Bile Acids ◽  
Cesarean Delivery ◽  
Vaginal Delivery ◽  
Intrahepatic Cholestasis ◽  
Mode Of Delivery ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Fetal Outcomes ◽  
Increased Risk ◽  
Total Bile Acids ◽  
Cholestasis Of Pregnancy

Abstract To assess the associations between mode of delivery and pregnancy outcomes in patients with intrahepatic cholestasis of pregnancy (ICP) based on the severity of maternal hypercholanemia. A hospital-based retrospective cohort study was performed between January 1, 2015, and December 31, 2019. Among the 177 women with mild total bile acids, 123 (69.5%) had a vaginal delivery and 54 (30.5%) underwent a cesarean delivery, of which 42 (23.7%) were planned and 12 (6.8%) were unplanned. Among the 50 severe ICP women, 13 (26.0%) had a vaginal delivery and 37 (74.0%) underwent a cesarean delivery, of which 26 (52.0%) were planned and 11 (22.0%) were unplanned. Severe ICP was associated with an increased risk of preterm delivery (P < 0.001), low birthweight (P=0.001), and neonatal intensive care unit admission (P < 0.001). Women with severe ICP (aOR, 5.017; 95% CI 1.848–13.622), planned cesarean delivery (aOR, 5.444; 95%CI 1.723–17.203), or unplanned cesarean delivery (aOR, 5.792; 95%CI 1.384–24.236) had increased risks of adverse fetal outcomes compared to controls. Both planned and unplanned cesarean delivery are associated with a higher incidence of adverse fetal outcomes and severe ICP than vaginal delivery.

scholarly journals Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine – Section on Maternal Disorders

2021 ◽  
Vol 81 (08) ◽  
pp. 922-939
Author(s):  
Carsten Hagenbeck ◽  
Amr Hamza ◽  
Sven Kehl ◽  
Holger Maul ◽  
Frank Lammert ◽  
...  
Keyword(s):  
Bile Acid ◽  
Intrahepatic Cholestasis ◽  
Perinatal Outcomes ◽  
Fetal Monitoring ◽  
Fetal Outcome ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Bile Acid Level ◽  
Cardinal Symptom ◽  
Cholestasis Of Pregnancy ◽  
Meconium Stained Amniotic Fluid

AbstractIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disease specific to pregnancy. The cardinal symptom of pruritus and a concomitant elevated level of bile acids in the serum and/or alanine aminotransferase (ALT) are suggestive for the diagnosis. Overall, the maternal prognosis is good. The fetal outcome depends on the bile acid level. ICP is associated with increased risks for adverse perinatal outcomes, including preterm delivery, meconium-stained amniotic fluid, and stillbirth. Acute fetal asphyxia and not chronic uteroplacental dysfunction leads to stillbirth. Therefore, predictive fetal monitoring is not possible. While medication with ursodeoxycholic acid (UDCA) improves pruritus, it has not been shown to affect fetal outcome. The indication for induction of labour depends on bile acid levels and gestational age. There is a high risk of recurrence in subsequent pregnancies.

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