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Intrahepatic Cholestasis

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https://www.readbyqxmd.com/read/28805978/obeticholic-acid-a-selective-farnesoid-x-receptor-agonist-regulates-bile-acid-homeostasis-in-sandwich-cultured-human-hepatocytes
#1
Yuanyuan Zhang, Jonathan P Jackson, Robert L St Claire, Kimberly Freeman, Kenneth R Brouwer, Jeffrey E Edwards
Farnesoid X receptor (FXR) is a master regulator of bile acid homeostasis through transcriptional regulation of genes involved in bile acid synthesis and cellular membrane transport. Impairment of bile acid efflux due to cholangiopathies results in chronic cholestasis leading to abnormal elevation of intrahepatic and systemic bile acid levels. Obeticholic acid (OCA) is a potent and selective FXR agonist that is 100-fold more potent than the endogenous ligand chenodeoxycholic acid (CDCA). The effects of OCA on genes involved in bile acid homeostasis were investigated using sandwich-cultured human hepatocytes...
August 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28799842/midterm-safety-and-efficacy-of-irreversible-electroporation-of-malignant-liver-tumors-located-close-to-major-portal-or-hepatic-veins
#2
Martina Distelmaier, Alexandra Barabasch, Philipp Heil, Nils A Kraemer, Peter Isfort, Sebastian Keil, Christiane K Kuhl, Philipp Bruners
Purpose To investigate the efficacy and safety of irreversible electroporation (IRE) in the treatment of hepatic tumors not suitable for thermal ablation (radiofrequency ablation [RFA] or microwave ablation). Materials and Methods This was an institutional review board-approved prospective study in 29 patients (15 men, 14 women; mean age, 63 years ± 12 [standard deviation]) with 43 primary (n = 8) or secondary (n = 35) malignant liver tumors who underwent computed tomography (CT)-guided IRE. All target tumors were located immediately adjacent to major hepatic veins, portal veins, or both; thus, they were not considered suitable for RFA or microwave ablation...
August 11, 2017: Radiology
https://www.readbyqxmd.com/read/28798896/pregnancy-outcomes-in-hiv-infected-women-experience-from-a-tertiary-care-center-in-india
#3
Vatsla Dadhwal, Aparna Sharma, Kavita Khoiwal, Dipika Deka, Plaboni Sarkar, P Vanamail
BACKGROUND AND OBJECTIVES: There is conflicting data on the effect of HIV infection as well as antiretroviral therapy (ART) on pregnancy outcome. The objectives of this study were to compare pregnancy outcomes in women with and without HIV infection, and to evaluate the effect of HAART on pregnancy in HIV-infected women. METHODS: This is a prospective case record analysis of 212 HIV-infected women delivering between 2002 and 2015, in a tertiary health care center in India...
2017: International Journal of MCH and AIDS
https://www.readbyqxmd.com/read/28759700/interventions-for-treating-intrahepatic-cholestasis-in-people-with-sickle-cell-disease
#4
REVIEW
Arturo J Martí-Carvajal, Cristina Elena Martí-Amarista
BACKGROUND: Sickle cell disease is the most common hemoglobinopathy occurring worldwide and sickle cell intrahepatic cholestasis is a complication long recognized in this population. Cholestatic liver diseases are characterized by impaired formation or excretion (or both) of bile from the liver. There is a need to assess the clinical benefits and harms of the interventions used to treat intrahepatic cholestasis in people with sickle cell disease. This is an update of a previously published Cochrane Review...
July 31, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28757171/genetic-determinants-of-cholangiopathies-molecular-and-systems-genetics
#5
REVIEW
Matthias C Reichert, Rabea A Hall, Marcin Krawczyk, Frank Lammert
Familial cholangiopathies are rare but potentially severe diseases. Their spectrum ranges from fairly benign conditions as, for example, benign recurrent intrahepatic cholestasis to low-phospholipid associated cholelithiasis and progressive familial intrahepatic cholestasis (PFIC). Many cholangiopathies such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) affect first the bile ducts ("ascending pathophysiology") but others, such as PFIC, start upstream in hepatocytes and cause progressive damage "descending" down the biliary tree and leading to end-stage liver disease...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754450/pathogenesis-of-biliary-fibrosis
#6
REVIEW
Massimo Pinzani, Tu Vinh Luong
Chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, and, ultimately, to the development of cirrhosis. However, the precise relationship between cholestasis, in its broad meaning, and liver tissue fibrosis is still poorly defined. Fibrogenesis is currently viewed as a dynamic process that appears strictly related to the extent and duration of parenchymal injury. This relationship is clearly evident in the presence of reiterative hepatocellular necrosis due to viral infection or alcohol abuse...
July 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28733223/sequencing-of-fic1-bsep-and-mdr3-in-a-large-cohort-of-patients-with-cholestasis-revealed-a-high-number-of-different-genetic-variants
#7
Carola Dröge, Michele Bonus, Ulrich Baumann, Caroline Klindt, Elke Lainka, Simone Kathemann, Florian Brinkert, Enke Grabhorn, Eva-Doreen Pfister, Daniel Wenning, Alexander Fichtner, Daniel N Gotthardt, Karl Heinz Weiss, Patrick McKiernan, Ratna Dua Puri, I C Verma, Stefanie Kluge, Holger Gohlke, Lutz Schmitt, Ralf Kubitz, Dieter Häussinger, Verena Keitel
BACKGROUND&AIMS: The bile salt export pump (BSEP, ABCB11), multidrug resistance protein 3 (MDR3, ABCB4) and the ATPase familial intrahepatic cholestasis 1 (FIC1, ATP8B1) mediate bile formation. Mutations in these genes underlie cholestatic liver diseases ranging from intrahepatic cholestasis of pregnancy, benign recurrent intrahepatic cholestasis or low phospholipid-associated cholelithiasis to progressive familial intrahepatic cholestasis. METHODS: Coding exons with flanking intron regions of ATP8B1, ABCB11, and ABCB4 were sequenced in cholestatic patients with assumed genetic cause...
July 19, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28730136/early-diagnosis-of-abcb11-spectrum-liver-disorders-by-next-generation-sequencing
#8
Su Jeong Lee, Jung Eun Kim, Byung-Ho Choe, An Na Seo, Han-Ik Bae, Su-Kyeong Hwang
PURPOSE: The goal of this study was the early diagnosis of ABCB11 spectrum liver disorders, especially those focused on benign recurrent intrahepatic cholestasis and progressive familial intrahepatic cholestasis. METHODS: Fifty patients presenting neonatal cholestasis were evaluated to identify underlying etiologies. Genetic analysis was performed on patients suspected to have syndromic diseases or ABCB11 spectrum liver disorders. Two families with proven ABCB11 spectrum liver disorders were subjected to genetic analyses to confirm the diagnosis and were provided genetic counseling...
June 2017: Pediatric Gastroenterology, Hepatology & Nutrition
https://www.readbyqxmd.com/read/28710680/development-of-a-novel-tool-to-assess-the-impact-of-itching-in-pediatric-cholestasis
#9
Binita M Kamath, Linda Abetz-Webb, Ciara Kennedy, Bonnie Hepburn, Martha Gauthier, Nathan Johnson, Sharon Medendorp, Alejandro Dorenbaum, Lora Todorova, Benjamin L Shneider
OBJECTIVES: The aim was to develop a clinical outcome assessment (COA) for itching in children with cholestatic pruritus. METHODS: This prospective study aimed to enroll patients aged 4-30 years with Alagille syndrome (ALGS) or progressive familial intrahepatic cholestasis type 1 and caregivers of patients aged 5 months to 14 years. Eligible patients experienced itching during ≥3 of the 7 days before enrollment and had not undergone liver transplant or surgical interruption of the enterohepatic circulation...
July 14, 2017: Patient
https://www.readbyqxmd.com/read/28697498/effect-of-histone-deacetylase-hdac3-on-cytokines-il-18-il-12-and-tnf-%C3%AE-in-patients-with-intrahepatic-cholestasis-of-pregnancy
#10
Yong Shao, Jing Chen, Jiao Zheng, Cai-Ru Liu
BACKGROUND/AIMS: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is poorly understood. OBJECTIVE: This study aimed to explore the possible effect of HDAC3 (histone deacetylase) on cytokines IL-18, IL-12 and TNF-α in ICP. METHODS: Serum levels of cytokines IL-18, IL-12 and TNF-α, bile acids and hepatic function parameters were measured. The expression of HDAC3 in the placenta was determined by immunohistochemistry (IHC), western blotting and RT-PCR...
July 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28696845/decompensated-cirrhosis-and-sickle-cell-disease-case-reports-and-review-of-the-literature
#11
Roberta D'Ambrosio, Marco Maggioni, Maria F Donato, Pietro Lampertico, Maria D Cappellini, Giovanna Graziadei
Although its prevalence is unknown, liver involvement by sickle cell disease is not uncommon and encompasses different clinical spectra including non cholestatic and cholestatic disorders. Few data have been provided on chronic sickle cell intrahepatic cholestasis (SCIC) clinical course, although cirrhosis has been reported in sickle cell disease. However, no effective therapeutic approaches have been recognized either to prevent or treat this condition. Here we present two cases of adult sickle cell disease patients with decompensated cirrhosis...
March 2017: Hemoglobin
https://www.readbyqxmd.com/read/28691322/bile-acid-levels-and-risk-of-adverse-perinatal-outcomes-in-intrahepatic-cholestasis-of-pregnancy-a-meta-analysis
#12
Donghua Cui, Yongxing Zhong, Lin Zhang, Hechun Du
AIM: We aimed to determine the association between maternal total bile acid (TBA) levels and the risks of adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) based on a meta-analysis study. METHODS: We searched PubMed for articles published from 2000 to 2015 with a focus on ICP and restriction to the English language. The main perinatal outcomes were preterm birth (PTB), meconium-stained amniotic fluid (MSAF), asphyxia, or respiratory distress syndrome (RDS)...
July 10, 2017: Journal of Obstetrics and Gynaecology Research
https://www.readbyqxmd.com/read/28688656/notch-signaling-promotes-ductular-reactions-in-biliary-atresia
#13
Jessica A Zagory, William Dietz, Alex Park, Michael Fenlon, Jiabo Xu, Sarah Utley, Nirmala Mavila, Kasper S Wang
BACKGROUND: Biliary atresia (BA) is a congenital, progressive, fibro-obliterative disease of the extrahepatic biliary tree and the most common cause of end-stage liver disease in children. BA is characterized by extensive intrahepatic proliferating ductular reactions that may contribute to biliary fibrosis. Lineage tracing during experimental cholestasis indicates that cells within ductular reactions derive from PROM1-expressing hepatic progenitor cells. Given the role of Notch signaling in normal biliary development, we hypothesize that activated Notch signaling promotes the formation of ductular reactions in BA...
July 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28683534/a-case-of-alagille-syndrome-presenting-with-chronic-cholestasis-in-an-adult
#14
Jihye Kim, Bumhee Yang, Namyoung Paik, Yon Ho Choe, Yong-Han Paik
Alagille syndrome (AGS) is a complex multisystem disorder that involves mainly the liver, heart, eyes, face, and skeleton. The main associated clinical features are chronic cholestasis due to a paucity of intrahepatic bile ducts, congenital heart disease primarily affecting pulmonary arteries, vertebral abnormalities, ocular embryotoxon, and peculiar facies. The manifestations generally become evident at a pediatric age. AGS is caused by defects in the Notch signaling pathway due to mutations in JAG1 or NOTCH2...
July 7, 2017: Clinical and Molecular Hepatology
https://www.readbyqxmd.com/read/28680707/intrahepatic-cholestasis-of-pregnancy-leading-to-severe-vitamin-k-deficiency-and-coagulopathy
#15
Maria Maldonado, Ali Alhousseini, Michael Awadalla, Jay Idler, Robert Welch, Karoline Puder, Manasi Patwardhan, Bernard Gonik
Intrahepatic cholestasis of pregnancy is seldom associated with significant vitamin K deficiency. We report a case of a 16-year-old primigravid patient at 24 weeks and 3 days of gestation who presented with pruritus, hematuria, and preterm labor. Laboratory work-up showed severe coagulopathy with Prothrombin Time (PT) of 117.8 seconds, International Normalized Ratio (INR) of 10.34, and elevated transaminases suggestive of intrahepatic cholestasis of pregnancy. Her serum vitamin K level was undetectable (<0...
2017: Case Reports in Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28669684/urinary-metabolomic-analysis-of-intrahepatic-cholestasis-of-pregnancy-based-on-high-performance-liquid-chromatography-mass-spectrometry
#16
Li Ma, Xiaoqing Zhang, Feng Pan, Yue Cui, Ting Yang, Linlin Deng, Yong Shao, Min Ding
BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP), a pregnancy-related liver disease, leads to complications for both mothers and fetuses. Metabolomic approach has been applied to maternal-fetal medicine. The global metabolomic alterations that are specific in ICP as yet have not been investigated. METHODS: Based on high performance liquid chromatography/hybrid quadrupole time-of-flight (HPLC/Q-TOF) mass spectrometry, the untargeted metabolomics was used to analyze the changes of urinary metabolites between ICP group and the control group...
August 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#17
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28660384/increased-hepatic-abca1-transporter-is-associated-with-hypercholesterolemia-in-a-cholestatic-rat-model-and-primary-biliary-cholangitis-patients
#18
Yasuaki Takeyama, Yuko Uehara, Akira Anan, Daisuke Morihara, Keiji Yokoyama, Kazuhide Takata, Takashi Tanaka, Makoto Irie, Kaoru Iwata, Satoshi Shakado, Tetsuro Sohda, Shotaro Sakisaka
Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls (P < 0...
June 28, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28647962/-effect-of-endoplasmic-reticulum-stress-in-trophocytes-on-the-pathogenesis-of-intrahepatic-cholestasis-of-pregnancy
#19
Y Yu, C L Zhou, T T Yu, X J Han, H Y Shi, H Z Wang, J J Shen, J He
Objective: To evaluate the effect of endoplasmic reticulum stress in trophocytes, in patients with intrahepatic cholestasis of pregnancy (ICP). Methods: Sixty-one pregnant women who were hospitalized in Women's Hospital, School of Medicine, Zhejiang University from January to December 2015 were recruited. Thirty-one women who were diagnosed as ICP were defined as the ICP group and 30 healthy pregnant women were defined as the control group. The localization and expression intensity of glucose regulated protein 78 (GRP-78) in placental tissues were detected by immunohistochemistry technique...
June 25, 2017: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/28646549/inhibition-of-jnk-signaling-mediates-ppar%C3%AE-dependent-protection-against-intrahepatic-cholestasis-by-fenofibrate
#20
Manyun Dai, Julin Yang, Minzhu Xie, Jiao Lin, Min Luo, Huiying Hua, Gangming Xu, Hante Lin, Danjun Song, Yuqing Cheng, Bin Guo, Jinshun Zhao, Frank J Gonzalez, Aiming Liu
BACKGROUND AND PURPOSE: Fenofibrate, a PPARα agonist, is the most widely prescribed drug for the treatment of hyperlipidemia. Although fibrate drugs were reported to be beneficial for cholestasis, the underlying mechanism has not been determined. EXPERIMENTAL APPROACH: Wild-type mice and Pparα-null mice were orally pretreated with fenofibrate for three days, following which ANIT was administered to induce cholestasis. The potent experimental PPARα agonist WY14643 was used to validate the role of PPARα, and the JNK inhibitor SP600125 was employed to explore the role of the JNK pathway in cholestatic liver injury...
June 23, 2017: British Journal of Pharmacology
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