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pathophysiology cholestasis of pregnancy

Maria Teresa Mella, Katherine Kohari, Richard Jones, Juan Peña, Lauren Ferrara, Joanne Stone, Luca Lambertini
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) affects 0.2-2% of pregnant women. While the maternal clinical course of ICP is usually benign, the fetal effects can be severe spanning from spontaneous preterm birth to fetal demise to long term effects on the health of the progeny. ICP is characterized by high maternal serum levels of bile acids and placental and hepatic bile acids accumulation. Intrahepatic cholestasis, in the non-pregnant state, has been also linked to alterations of the mitochondrial activity attributed to high oxidative stress rates driven by high intracellular bile acids concentrations...
September 2016: Placenta
Antonín Pařízek, Martin Hill, Michaela Dušková, Libor Vítek, Marta Velíková, Radmila Kancheva, Patrik Šimják, Michal Koucký, Zuzana Kokrdová, Karolína Adamcová, Andrej Černý, Zdeněk Hájek, Luboslav Stárka
Intrahepatic cholestasis of pregnancy (ICP) is a common liver disorder, mostly occurring in the third trimester. ICP is defined as an elevation of serum bile acids, typically accompanied by pruritus and elevated activities of liver aminotransferases. ICP is caused by impaired biliary lipid secretion, in which endogenous steroids may play a key role. Although ICP is benign for the pregnant woman, it may be harmful for the fetus. We evaluated the differences between maternal circulating steroids measured by RIA (17-hydroxypregnenolone and its sulfate, 17-hydroxyprogesterone, and cortisol) and GC-MS (additional steroids), hepatic aminotransferases and bilirubin in women with ICP (n = 15, total bile acids (TBA) >8 μM) and corresponding controls (n = 17)...
2016: PloS One
Caroline Ovadia, Catherine Williamson
Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, is a pruritic condition of pregnancy characterized by an underlying elevation in circulating bile acids and liver derangement, and associated with adverse fetal outcomes, such as preterm labor and stillbirth. Limited understanding of the underlying pathophysiology and mechanisms involved in adverse outcomes has previously restricted treatment options and pregnancy management. Recent advances in these research fields provide tantalizing targets to improve the care of pregnant women affected by this condition...
May 2016: Clinics in Dermatology
Jieying Gao, Biao Xu, Xiaoqing Zhang, Yue Cui, Linlin Deng, Zhenghu Shi, Yong Shao, Min Ding
BACKGROUND: Given the potential influence of aberrant bile acid metabolism on glucose homeostasis, we hypothesized that serum bile acid metabolism is altered in gestational diabetes mellitus (GDM). We characterized the metabolic profiling changes of serum bile acids in GDM and to find the potential biomarkers for the diagnosis and differential diagnosis of GDM. METHODS: Based on ultrahigh performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, a targeted metabolomics study that involved targeted and untargeted screening techniques was performed to explore the changes in serum bile acid metabolism of GDM cases, intrahepatic cholestasis of pregnancy (ICP) cases and healthy controls...
August 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
Serdar Başaranoğlu, Elif Ağaçayak, Feyzullah Uçmak, Senem Yaman Tunç, Aysegül Deregözü, Zeynep Meltem Akkurt, Nurullah Peker, Mustafa Acet, Hatice Yüksel, Talip Gül
AIM: The present study aimed to determine the levels of total cholesterol, triglycerides (TG), low-density lipoproteins (LDL), high-density lipoproteins (HDL), and vitamins B1 and B2 in intrahepatic cholestasis of pregnancy (ICP) patients, and to evaluate if these were involved in the pathophysiology of the disease. METHODS: The prospective randomized study included 35 pregnant patients who were admitted to the Gynecology and Obstetrics Polyclinic, Faculty of Medicine at Dicle University and who were diagnosed with ICP (Group 1), and 40 healthy pregnant women who were admitted in the same period and who had no systemic diseases that might complicate the pregnancy during the pregnancy follow-up (Group 2)...
April 6, 2016: Journal of Perinatal Medicine
Peter H Dixon, Catherine Williamson
A number of liver disorders are specific to pregnancy. Amongst these, intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis (OC), is the commonest, affecting approximately 1 in 140 UK pregnancies. Patients commonly present in the third trimester with severe pruritus and deranged serum liver tests; bile acids are elevated, in severe cases >40 μmol/L. Although the disease is considered relatively benign for the mother, increased rates of adverse fetal outcomes, including stillbirth, are associated with ICP...
April 2016: Clinics and Research in Hepatology and Gastroenterology
Ali Ozler, Derya Ucmak, Mehmet Siddik Evsen, Ibrahim Kaplan, Bilal Elbey, Mustafa Arica, Muhsin Kaya
INTRODUCTION: The purpose of this study was to investigate levels of inflammatory cytokines such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and neopterin and oxidative stress status in patients with intrahepatic cholestasis of pregnancy (ICP) as well as their potential role in the pathophysiology. MATERIAL AND METHODS: Thirty patients with ICP (Group 1) and 30 healthy pregnant women (Group 2) were included in this prospective case-control study. Levels of IL-6, TNF-α and neopterin were determined in both of the groups...
2014: Central-European Journal of Immunology
Yukihiro Nakanishi, Romil Saxena
CONTEXT: Diseases of the proximal pathways of the biliary system can be divided into those that affect the interlobular bile ducts and those that affect the bile canaliculi. The former include primary biliary cirrhosis, small-duct variant of primary sclerosing cholangitis, graft-versus-host disease, and drug-induced liver injury, whereas the latter include progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis, intrahepatic cholestasis of pregnancy, and drug-induced liver injury...
July 2015: Archives of Pathology & Laboratory Medicine
W Wei, Y Y Hu
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder unique to pregnancy that is associated with increased rates of fetal distress and demise. While acute hypoxia is believed to cause the pathophysiology of ICP, direct molecular evidence for this is lacking. Here, we analyzed expression of three hypoxia-regulated genes and several of their downstream target genes involved in glucose metabolism in placenta. METHODS: Placental tissue was collected from 20 women with normal pregnancies and 20 women with ICP...
September 2014: Placenta
B Moreno, A López Faraldo
Intrahepatic cholestasis of pregnancy is a reversible disease of variable frequency. The pathophysiology involves an increase of the bile acids in the fetal blood of the mother and the fetus. The high concentrations of the bile acids cause maternal pruritus and high perinatal morbimortality. Primary Care physicians in close contact with the patient must have a high index of suspicion when faced with typical symptoms of cholestasis, such as generalized pruritus in women in the second or third trimester of gestation to be able to act on the consequences...
October 2014: Semergen
Ting Zhang, Yueshuai Guo, Xuejiang Guo, Tao Zhou, Daozhen Chen, Jingying Xiang, Zuomin Zhou
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and associated with increased risks in fetal complications. Currently, the exact cause of this disease is unknown. In this study we aim to investigate the potential proteins in placenta, which may participate in the molecular mechanisms of ICP-related fetal complications using iTRAQ-based proteomics approach. METHODS: The iTRAQ analysis combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to separate differentially expressed placental proteins from 4 pregnant women with ICP and 4 healthy pregnant women...
2013: PloS One
Vinita Gurung, Philippa Middleton, Stephen J Milan, William Hague, Jim G Thornton
BACKGROUND: Obstetric cholestasis has been linked to adverse maternal and fetal/neonatal outcomes. As the pathophysiology is poorly understood, therapies have been empiric. The first version of this review, published in 2001, and including nine randomised controlled trials involving 227 women, concluded that there was insufficient evidence to recommend any of the interventions alone or in combination. This is the first update. OBJECTIVES: To evaluate the effectiveness and safety of therapeutic and delivery interventions in women with cholestasis of pregnancy...
2013: Cochrane Database of Systematic Reviews
Lauren P Rimoin, Shawn G Kwatra, Gil Yosipovitch
There have been considerable advances in our understanding of the pathophysiology of pruritus in recent years. The purpose of this review was to highlight itch entities in women, and in particular pruritic vulvar dermatoses that women experience among different age groups. Unique temporal shifts may contribute to the etiology of many of these conditions. These changes lead to cyclical changes in the skin's basic composition. Specifically, estrogen receptors have been detected on keratinocytes that respond to rising and falling levels of estrogen...
March 2013: Dermatologic Therapy
Annarosa Floreani, Diego Caroli, Roberta Lazzari, Alessia Memmo, Elisa Vidali, Davide Colavito, Antonello D'Arrigo, Alberta Leon, Roberto Romero, Maria Teresa Gervasi
AIM: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. METHODS: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. RESULTS: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0...
September 2013: Journal of Maternal-fetal & Neonatal Medicine
Y Yin, Q Y Zhu, S J Ren, D M Wang
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is a reversible cholestatic liver disease of undefined etiology and pathogenesis. It is likely associated with dyslipidemia. However, the explanation for the role of dyslipidemia is not clear. We hypothesized that an increased oxidized low-density lipoprotein (oxLDL) and lectin-like oxidized LDL receptor-1 (LOX-1) may play a crucial role in the development of the disease. Thus, the aim of this study was to investigate the plasma oxLDL level and LOX-1 expression in placentas from women with ICP...
2012: Clinical and Experimental Obstetrics & Gynecology
Ralf Kubitz, Carola Dröge, Jan Stindt, Katrin Weissenberger, Dieter Häussinger
The bile salt export pump (BSEP) is the major transporter for the secretion of bile acids from hepatocytes into bile in humans. Mutations of BSEP are associated with cholestatic liver diseases of varying severity including progressive familial intrahepatic cholestasis type 2 (PFIC-2), benign recurrent intrahepatic cholestasis type 2 (BRIC-2) and genetic polymorphisms are linked to intrahepatic cholestasis of pregnancy (ICP) and drug-induced liver injury (DILI). Detailed analysis of these diseases has considerably increased our knowledge about physiology and pathophysiology of bile secretion in humans...
December 2012: Clinics and Research in Hepatology and Gastroenterology
Huimin Wang, Ziru Yan, Minyue Dong, Xiaojun Zhu, Hanzhi Wang, Zhengping Wang
PURPOSE: To investigate whether bile acids transporters organic anion transporting polypeptides 1A2 (OATP1A2), organic anion transporting polypeptides 1B1 (OATP1B1), organic anion transporting polypeptides 1B3 (OATP1B3) were differently expressed in placenta of intrahepatic cholestasis of pregnancy (ICP). METHODS: Thirty pregnant women with ICP were recruited and 30 normal pregnant women served as control. The expression of mRNA and protein were analyzed by real-time PCR and Western blotting...
June 2012: Archives of Gynecology and Obstetrics
M P Beard, G W M Millington
During pregnancy, the mother undergoes changes to sustain and enable normal growth and development of the fetus. Common physiological changes include linea nigra, fibroepithelial polyps, striae, spider angioma, palmar erythema and pruritis gravidarum. However, there are some changes that are purely pathological, and these are termed the pregnancy-specific dermatoses (PSDs). The PSDs occur during pregnancy or in the immediate postpartum period. They do not include the various benign conditions or pre-existing dermatoses and tumours that may present or worsen with pregnancy...
January 2012: Clinical and Experimental Dermatology
Andreas E Kremer, Ronald P J Oude Elferink, Ulrich Beuers
Pruritus is frequently reported by patients with cholestatic hepatobiliary diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy and hereditary cholestatic syndromes, but may accompany almost any other liver disease. Increased concentrations of bile salts, histamine, progesterone metabolites or endogenous opioids have been controversially discussed as potential pruritogens in cholestasis in the past. Most recently, novel insights unravelled lysophosphatidic acid (LPA), a potent neuronal activator, as a potential pruritogen in pruritus of cholestasis...
February 2011: Clinics and Research in Hepatology and Gastroenterology
Bruno Stieger, Andreas Geier
INTRODUCTION: Drug-induced cholestasis, intrahepatic cholestasis of pregnancy and viral hepatitis are acquired forms of liver disease. Cholestasis is a pathophysiologic state with impaired bile formation and subsequent accumulation of bile salts in hepatocytes. The bile salt export pump (BSEP) (ABCB11) is the key export system for bile salts from hepatocytes. AREAS COVERED: This article provides an introduction into the physiology of bile formation followed by a summary of the current knowledge on the key bile salt transporters, namely, the sodium-taurocholate co-transporting polypeptide NTCP, the organic anion transporting polypeptides (OATPs), BSEP and the multi-drug resistance protein 3...
April 2011: Expert Opinion on Drug Metabolism & Toxicology
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