Molecular pathogenesis of intrahepatic cholestasis of pregnancy

Author(s):  
Marco Arrese ◽  
Rocio I.R. Macias ◽  
Oscar Briz ◽  
Maria J. Perez ◽  
Jose J.G. Marin

Intrahepatic cholestasis of pregnancy (ICP) occurs mainly in the third trimester and is characterised by pruritus and elevated serum bile acid levels. ICP is associated with an increased perinatal risk and higher rates of foetal morbidity and mortality. Although the pathogenesis of this disease is unknown, a genetic hypersensitivity to female hormones (oestrogen and/or progesterone) or their metabolites is thought to impair bile secretory function. Recent data suggest that mutations or polymorphisms of genes expressing hepatobiliary transport proteins or their nuclear regulators may contribute to the development and/or severity of ICP. Unidentified environmental factors may also influence pathogenesis of the disease. This review summarises current knowledge on the potential mechanisms involved in ICP at the molecular level.

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 22 (1) ◽  
Author(s):  
Cem Yaşar Sanhal ◽  
Korkut Dağlar ◽  
Özgür Kara ◽  
Ayşe Kırbaş ◽  
Dilek Uygur ◽  
...  

<p>Objective: To evaluate the presence of any seasonal variation in the frequency of intrahepatic cholestasis of pregnancy (ICP).<br />Study Design: A total of 126 cases with ICP were compared with a cohort of 37614 pregnant women who delivered. The diagnosis ICP was performed on the basis of severe itching and the absence of dermal rash and any other hepatic disease, with the co-existence of elevated serum aminotransferase levels and/or serum bile acid concentration. For each month and season, observed and expected ICP rates were analysed and compared by using chi-square statistics. Multivariate logistic regression was performed to investigate certain parameters on cumulative risk. <br />Results: A significantly lower frequency of ICP in winter (6/126 (4.8%), p=0.001) and a significantly higher frequency in spring (44/126 (34.9%), p=0.034) were detected. A 2.1 and 3.8-fold higher risk were found for the nulliparity and the twin pregnancy, respectively. Logistic regression analysis confirmed the significant (10-fold) decrease in the frequency of ICP in winter. The significance of spring did not persist after the adjustment.<br />Conclusion: Main outcome of the study points at seasonality in ICP frequency. Future studies in different populations may reveal data about factors that interact with seasonality and playing roles in ICP. <br /><br /></p>


2016 ◽  
Vol 06 (02) ◽  
pp. 063-065
Author(s):  
Precilla D'silva ◽  
Jasmine Maria Lobo ◽  
Akhila Mol Babu

AbstractIntrahepatic cholestasis of pregnancy (ICP) is a cholestatic disorder characterized by pruritus, elevated serum aminotransferases and bile acid levels with gradual onset in the second or third trimester of pregnancy, and spontaneous relief of signs and symptoms within two to three weeks after delivery.


2021 ◽  
Vol 81 (08) ◽  
pp. 940-947
Author(s):  
Stanisław M. Jurk ◽  
Andreas E. Kremer ◽  
Ekkehard Schleussner

AbstractIntrahepatic 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.


Author(s):  
Sangeeta Yadav ◽  
Amit Goel ◽  
Raghavendra Lingaiah ◽  
Mandakini Pradhan ◽  
Harshita Katiyar ◽  
...  

Author(s):  
Bhawna Sharma ◽  
Neetu Arora ◽  
Kusum Dogra ◽  
Kamal S. Negi

Background: Maternal, fetal, and neonatal outcomes in parturients with intrahepatic cholestasis of pregnancy (ICP) have been retrospectively documented. We aimed to present pregnancy outcomes of parturients with ICP who underwent delivery. The study was conducted during a 1-year period in a tertiary care centre.Methods: Data from 1 January to 31 December 2017 were collected to identify parturients with ICP.Results: Almost 3/4th of births came to a vaginal delivery (76.74%) and only 10 parturients had cesarean delivery. 4 of 10 parturients underwent nonelective cesarean section, while 6 had elective cesarean delivery. 15.15 % vaginal deliveries were instrumental. The most common indications for emergency LSCS and instrumental deliveries was fetal distress followed by failure to progress of labour. Most births occurred at or after 37 weeks of gestation (65%).  Regarding neonatal outcomes in terms of birth weight and Apgar scores at 1 and 5 min, they were positive, as well.  None of the babies had Apgar score < 7 at 5 minutes. No case of perinatal death was observed.Conclusions: Although the results were generally positive, larger studies need to be conducted to evaluate the maternal and fetal outcomes in ICP and correlation with serum bile acid levels.


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.


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