Intrahepatic cholestasis of pregnancy: Molecular pathogenesis, diagnosis and management

Department of Internal Medicine III, Aachen University of Technology RWTH, Germany.
Journal of Hepatology (Impact Factor: 11.34). 01/2001; 33(6):1012-21. DOI: 10.1016/S0168-8278(00)80139-7
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Available from: Frank Lammert, Apr 25, 2015
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    • "It is characterized by elevated serum bile acids (SBA) and/or transaminases and pruritis. Genetic predisposition, ethnicity, raised steroid hormone levels, and environmental factors have been proposed to play a role in the pathogenesis of ICP [7] [16] . ICP has been found to be associated with an increased risk of adverse pregnancy outcomes, such as preterm delivery , meconium staining, low APGAR scores, increased neonatal unit admission, intrauterine fetal death (IUFD), gestational diabetes mellitus, and preeclampsia [1] [5] [27] . "
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    ABSTRACT: Abstract Aim: Our aim was to investigate whether any hematological changes readily detectable by simple complete blood count (CBC), as well as fasting and postprandial total serum bile acid (SBA) levels, have diagnostic values for the prediction of adverse pregnancy outcomes in intrahepatic cholestasis of pregnancy (ICP). Methods: A prospective, case control study was carried out including 217 pregnant women (117 women with ICP and 100 healthy controls). The main outcome measures investigated were preterm delivery, APGAR scores, and neonatal unit admission. A multivariate logistic regression model was used to identify the independent risk factors of adverse pregnancy outcomes. Results: Compared with controls, women with ICP had significantly higher mean platelet volume (MPV) (mean 10.2±1.0 vs. 11.0±1.3; P<0.001) and platelet distribution width (PDW) (mean 13.1±2.3 vs. 14.7±2.8; P<0.001) values. Analysis with logistic regression revealed that the probability of preterm delivery did not increase until MPV levels exceeded 11.2 fL [odds ratio (OR)=2.68, 95% confidence interval (CI)=1.13-6.32, P=0.025], and total bilirubin levels exceeded 0.6 mg/dL (OR=3.13, 95% CI=1.21-8.09, P=0.019). Considering the low APGAR scores, only increased postprandial total SBA levels of ≥51 μmol/L were found to be predictive significantly (OR=3.02, 95% CI=1.07-8.53, P=0.037). Conclusions: Our study suggests that increased MPV and total bilirubin levels are associated with preterm delivery, and increased postprandial total SBA levels are predictive for low APGAR in ICP patients.
    Journal of Perinatal Medicine 10/2014; DOI:10.1515/jpm-2014-0207 · 1.36 Impact Factor
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    • "It seems to be a multifactorial disease. The pathogenesis of ICP involves many factors, including genetic, hormonal, and environmental factors [3]. As yet, the pathogenesis and etiology of ICP remain elusive and incompletely understood. "
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    ABSTRACT: Objective To investigate differences in the placental proteomes of women with intrahepatic cholestasis of pregnancy (ICP) and those with a normal pregnancy. Methods Ten pregnant women diagnosed with ICP were recruited at the First People’s Hospital of Yuhang District from October 2011 to September 2012; 10 age-matched healthy pregnant women acted as controls. Total placental proteins were extracted and subjected to two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry to identify proteins that were differentially expressed in the two groups. Results In total, 37 protein spots with differentially expressed proteins were found. These comprised proteins involved in cytoskeleton activity, blood coagulation, and platelet activation as well as chaperones, heat shock proteins, RNA-binding and calcium-binding proteins, and various enzymes. Conclusion The placentas of women with ICP displayed significant proteome differences compared with women with a normal pregnancy. The results indicate that a variety of mechanisms and proteins may contribute to the development of ICP. Further verification and research are required to elucidate the exact roles of these proteins in ICP pathogenesis.
    International Journal of Gynecology & Obstetrics 09/2014; 126(3). DOI:10.1016/j.ijgo.2014.03.035 · 1.54 Impact Factor
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    • "ICP is more common in multiple pregnancies, probably due to the higher levels of estrogen and progesterone. Placental sex hormones affect the functions of membrane transport proteins of hepatocytes and thus affect biliary lipid secretion [20] . Environmental factors such as selenium deficiency might also contribute to the development of ICP [18] . "
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    ABSTRACT: Abstract Intrahepatic 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.
    Journal of Perinatal Medicine 08/2014; 43(2). DOI:10.1515/jpm-2014-0089 · 1.36 Impact Factor
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