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 ◽  
...  

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.

Author(s):  
Wojciech Jelski ◽  
Joanna Piechota ◽  
Karolina Orywal ◽  
Barbara Mroczko

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum bile acids concentration and other liver function tests. ICP  is connected with increased risk of fetal mortality, but is unfortunately detected quite late. Therefore, it is important to recognize the disease in its early stages. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP. Methods: Serum samples were taken for routine investigation from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women in the same time of pregnancy. For measurement of class I activity we used the spectrofluorometric methods. The total ADH activitiy was measured by the photometric method. Results: The analysis of results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41.3%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and total bile acids (TBA) concentration. The total ADH activity was also positively correlated with ALT, AST and total bile acids. Conclusion: We can state that the activity of class I alcohol dehydrogenase isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during this disease and is comparable with the value of other markers.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Olawumi Adaramodu ◽  
Anthony Kodzo-Grey Venyo

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.


2017 ◽  
Vol 07 (04) ◽  
pp. e223-e225 ◽  
Author(s):  
Adam Covach ◽  
William Rose

Objectives We report on a patient suffering from intractable itching secondary to intrahepatic cholestasis of pregnancy (ICP) unresponsive to conventional medical therapies. She was started on a regimen of therapeutic plasma exchange (TPE), which is often efficacious in relieving patient's itching from all causes of cholestasis, including ICP. Methods We performed a retrospective review of a patient's medical record. Results Following initial TPE, the patient reported dramatic relief of her itching and consequent insomnia. However, this effect was short lived, as subsequent TPE provided minimal relief, and may have actually worsened her itching. Out of concern for poor fetal outcomes, delivery was induced at 34 weeks gestational age. The child had an uncomplicated neonatal intensive care unit stay following delivery, and the mother reported > 90% relief of her symptoms 2 weeks after delivery. Conclusion TPE often provides longer term relief of itching because of ICP; however, it is not a panacea for these symptoms, and sometimes only delivery of the fetus can relieve maternal symptoms. In addition to the refractoriness to TPE, the case is also unusual for the early onset of ICP symptoms and the comorbidity of hepatitis C.


2019 ◽  
Vol 88 (4) ◽  
pp. 209-217
Author(s):  
Milena Gruszczyńska-Losy ◽  
Adrianna Mostowska ◽  
Łukasz Adamczak ◽  
Paweł Jagodziński ◽  
Ewa Wender-Ożegowska ◽  
...  

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.


2015 ◽  
Vol 43 (2) ◽  
Author(s):  
Patrik Šimják ◽  
Antonín Pařízek ◽  
Libor Vítek ◽  
Andrej Černý ◽  
Karolína Adamcová ◽  
...  

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.


2016 ◽  
Vol 94 (4) ◽  
pp. 402-407 ◽  
Author(s):  
Zhong Chen ◽  
Lingqing Hu ◽  
Mudan Lu ◽  
Zongji Shen

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.


2021 ◽  
Author(s):  
Joanna Piechota ◽  
Wojciech Jelski ◽  
Karolina Orywal ◽  
Barbara Mroczko

Abstract Background: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum total bile acids concentration (TBA) and increased liver enzymes. It is important to recognize the disease in its early stage. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP..Methods: Serum samples were taken from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women. For measurement of ADH we used the spectrofluorometric and photometric methods. Results: The results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and TBA concentration. The total ADH activity was also positively correlated with ALT, AST and TBA. Conclusion: We can state that the activity of class I ADH isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during ICP and is comparable with the value of other markers.


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