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Cholestasis

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https://www.readbyqxmd.com/read/29330965/intra-hepatic-bile-duct-primary-cilia-in-biliary-atresia
#1
Roberta Frassetto, Filippo Parolini, Salvatore Marceddu, Giulia Satta, Valeria Papacciuoli, Maria Antonia Pinna, Alessandra Mela, Giannina Secchi, Grazia Galleri, Roberto Manetti, Luisa Bercich, Vincenzo Villanacci, Antonio Dessanti, Roberto Antonucci, Francesco Tanda, Daniele Alberti, Kathleen B Schwarz, Maria Grazia Clemente
AIM: The etiopathogenesis of non-syndromic biliary atresia (BA) is obscure. The primary aim was to investigate intra-hepatic bile duct cilia (IHBC) in BA at the diagnosis and correlation with clinical outcome. The secondary aim was to analyze IHBC in routine paraffin-embedded liver biopsies using conventional scanning electron microscopy (SEM). METHODS: Surgical liver biopsies taken at the diagnosis from 22 BA infants (age range: 39 - 116 days) and from 8 children with non-BA chronic cholestasis (age range: 162 days -16,8 years) were evaluated for IHBC, both by immunofluorescence (IF) and by SEM...
January 13, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29328070/nerve-growth-factor-upregulates-sirtuin-1-expression-in-cholestasis-a-potential-therapeutic-target
#2
Ming-Shian Tsai, Po-Huang Lee, Cheuk-Kwan Sun, Ting-Chia Chiu, Yu-Chun Lin, I-Wei Chang, Po-Han Chen, Ying-Hsien Kao
This study investigated the regulatory role of nerve growth factor (NGF) in sirtuin 1 (SIRT1) expression in cholestatic livers. We evaluated the expression of NGF and its cognate receptors in human livers with hepatolithiasis and the effects of NGF therapy on liver injury and hepatic SIRT1 expression in a bile duct ligation (BDL) mouse model. Histopathological and molecular analyses showed that the hepatocytes of human diseased livers expressed NGF, proNGF (a precursor of NGF), TrkA and p75NTR, whereas only p75NTR was upregulated in hepatolithiasis, compared with non-hepatolithiasis livers...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29328026/clinical-efficacy-of-s-adenosylmethionine-in-patients-with-non-alcoholic-steatohepatitis-and-chronic-kidney-disease-i-ii-stage
#3
A Antoniv, N Antofiychuk, T Danylyshina, I Trefanenko, V Shuper
The article presents a theoretical generalization of the results of the clinical efficacy of S-adenosylmethionine in patients with non-alcoholic steatohepatitis (NASH) in comorbidity with obesity and chronic kidney disease (CKD) of the 1st-2nd stages. The objective of the article was to determine the likely effect of S-adenosylmethionine and Meldonium on the clinical course of non-alcoholic steatohepatitis (NASH) and chronic kidney disease (CKD) of the I-II stages. We examined 75 patients with NASH with comorbid obesity I degree and CKD I and II dgrees...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29321478/reprogramming-of-pro-inflammatory-human-macrophages-to-an-anti-inflammatory-phenotype-by-bile-acids
#4
Marianne Wammers, Anna-Kathrin Schupp, Johannes G Bode, Christian Ehlting, Stephanie Wolf, René Deenen, Karl Köhrer, Dieter Häussinger, Dirk Graf
Cholestasis is caused by autoimmune reactions, drug-induced hepatotoxicity, viral infections of the liver and the obstruction of bile ducts by tumours or gallstones. Cholestatic conditions are associated with impaired innate and adaptive immunity, including alterations of the cellular functions of monocytes, macrophages, NK cells and T-cells. Bile acids act as signalling molecules, affecting lipopolysaccharide (LPS)-induced cytokine expression in primary human macrophages. The present manuscript investigates the impact of bile acids, such as taurolithocholic acid (TLC), on the transcriptome of human macrophages in the presence or absence of LPS...
January 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29317337/heart-and-bile-acids-clinical-consequences-of-altered-bile-acid-metabolism
#5
REVIEW
Tharni Vasavan, Elisa Ferraro, Effendi Ibrahim, Peter Dixon, Julia Gorelik, Catherine Williamson
Cardiac dysfunction has an increased prevalence in diseases complicated by liver cirrhosis such as primary biliary cholangitis and primary sclerosing cholangitis. This observation has led to research into the association between abnormalities in bile acid metabolism and cardiac pathology. Approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy. Bile acids are directly implicated in this, causing QT interval prolongation, cardiac hypertrophy, cardiomyocyte apoptosis and abnormal haemodynamics of the heart...
January 6, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29317077/the-pruritus-of-cholestasis-from-bile-acids-to-opiate-agonists-relevant-after-all-these-years
#6
Nora V Bergasa
The pruritus of cholestasis is a maddening complication of liver disease. Increased opioidergic tone contributes to the pruritus of cholestasis, as evidenced by the amelioration of the symptom by opiate antagonists. Obeticholic acid, an agonist of the farnesoid receptor, has been approved for the treatment of primary biliary cholangitis, a disease characterized by cholestasis; this drug is associated with pruritus, the cause of which is unknown. In animal models, bile acids, which accumulate in the body as a result of cholestasis, have been reported to cause scratching behavior mediated by the TGR5 receptor, in an opioid-dependent manner, in laboratory animals...
January 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29316097/splicing-analysis-of-rare-novel-synonymous-or-intronic-variants-identified-in-abcb11-heterozygotes-presenting-as-progressive-intrahepatic-cholestasis-with-low-%C3%AE-glutamyltransferase
#7
Neng-Li Wang, Yi-Ling Qiu, Wen-Cai Guan, Gang Li, Yi Lu, Mei-Hong Zhang, Wei-Sha Luan, Jian-She Wang
AIM: To analyze the pathogenicity of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low γ-glutamyltransferase (GGT). METHODS: The enrolled variants were identified in ABCB11 between October 2009 and June 2016. The effects on pre-RNA splicing were analyzed by in silico tools and minigene splicing assay. RESULTS: There were 3 intronic (c.908+5G>A, c.2815-8A>G, and c...
January 9, 2018: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/29310470/new-therapies-target-the-toxic-consequences-of-cholestatic-liver-disease
#8
Peter L M Jansen
Introduction In most cholestatic liver diseases the primary cholestasis-causing lesions are located in the biliary tree and may be of (auto)immune origin. Bile salts are responsible for the secondary toxic consequences. Bile salt and nuclear hormone directed therapies primarily aim at improving this secondary toxic injury. In primary biliary cholangitis, trials show statistically significant responses on biochemical endpoints. Preclinical studies suggest that FXR- and PPAR-agonists, inhibitors of the apical sodium-dependent bile salt transporter (ASBT-inhibitors) and the C23 UDCA derivative nor-UDCA are promising agents for the treatment of primary sclerosing cholangitis (PSC)...
January 9, 2018: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29309877/development-of-a-mechanistic-biokinetic-model-for-hepatic-bile-acid-handling-to-predict-possible-cholestatic-effects-of-drugs
#9
Sylvia Notenboom, Karl M Weigand, Johannes H Proost, Marola M van Lipzig, Evita van de Steeg, Petra H H van den Broek, Rick Greupink, Frans G M Russel, Geny M M Groothuis
Drug-induced liver injury (DILI) is a common reason for drug withdrawal from the market. An important cause of DILI is drug-induced cholestasis. One of the major players involved in drug-induced cholestasis is the bile salt efflux pump (BSEP; ABCB11). Inhibition of BSEP by drugs potentially leads to cholestasis due to increased (toxic) intrahepatic concentrations of bile acids with subsequent cell injury. In order to investigate the possibilities for in silico prediction of cholestatic effects of drugs, we developed a mechanistic biokinetic model for human liver bile acid handling populated with human in vitro data...
January 5, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29307496/dithiothreitol-supplementation-mitigates-hepatic-and-renal-injury-in-bile-duct-ligated-mice-potential-application-in-the-treatment-of-cholestasis-associated-complications
#10
Reza Heidari, Vahid Ghanbarinejad, Hamidreza Mohammadi, Asrin Ahmadi, Athena Esfandiari, Negar Azarpira, Hossein Niknahad
Cholestasis is a disorder characterized by impaired bile flow and accumulation of cytotoxic bile acids in the liver. On the other hand, oxidative stress and its deleterious consequences seem to have a significant role in cholestasis-induced organ injury. Hence, antioxidants and thiol-reducing agents could have potential protective effect against this complication. The current investigation was designed to evaluate the effect of dithiothreitol (DTT) as a safe and clinically applicable thiol-reductant in cholestatic animals...
January 4, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29304564/unexplained-cholestasis-in-adults-and-adolescents-diagnostic-benefit-of-genetic-examination
#11
Luise Aamann, Nikolaj Ørntoft, Ida Vogel, Henning Grønbaek, Naja Becher, Hendrik Vilstrup, Peter Ott, Dorte Launholt Lildballe
OBJECTIVES: A few adult and adolescent patients with even severe cholestatic liver disease remain unexplained after standard diagnostic work-up. We studied the value of genetic examination in such patients and developed a panel of eight genes with known cholestatic associations. MATERIALS AND METHODS: Thirty-three patients with unexplained cholestasis despite a thorough clinical work-up were examined for sequence variations in the coding regions of the ABCB4, ABCB11, ABCC2, ABCG5, ATP8B1, JAG1, NOTCH2, and UGT1A1 genes and the promoter region of UGT1A1 by massive parallel sequencing of DNA extracted from whole blood...
January 5, 2018: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/29302103/babesia-odocoilei-as-a-cause-of-mortality-in-captive-cervids-in-canada
#12
Amélie Mathieu, Adriana R Pastor, Charlene N Berkvens, Carolyn Gara-Boivin, Michel Hébert, Alexandre N Léveillé, John R Barta, Dale A Smith
Nine cases of fatal infection with Babesia odocoilei were confirmed in reindeer (Rangifer tarandus tarandus) and elk (Cervus canadensis) housed in zoological institutions located in southern Quebec, Ontario, and Manitoba, Canada between 2013 and 2016. All animals died of a hemolytic crisis. Frequent postmortem findings were extensive hemorrhage, pigmenturia, and intrahepatic cholestasis. The described ante- and postmortem signs are consistent with those of previously reported cases in the United States. Diagnosis was confirmed in all cases by polymerase chain reaction performed on DNA extracted from whole blood or frozen spleen...
January 2018: Canadian Veterinary Journal. la Revue Vétérinaire Canadienne
https://www.readbyqxmd.com/read/29300488/atp-binding-cassette-transporter-a-subfamily-8-is-a-sinusoidal-efflux-transporter-for-cholesterol-and-taurocholate-in-mouse-and-human-liver
#13
Kazunari Sasaki, Masanori Tachikawa, Yasuo Uchida, Satoshi Hirano, Fumito Kadowaki, Michitoshi Watanabe, Sumio Ohtsuki, Tetsuya Terasaki
The ATP-binding cassette (ABC) transporter A subfamily 8 (ABCA8) belongs to the ABCA6-like transporters subgroup, which is distinct from the ABCA1-like subgroup in the ABCA family. The expression and function of the short-size human ABCA8 lacking one of the two ATP-binding domains for ATP hydrolysis, which are regularly present in the other ABCA transporters, have been reported. However, the functional differences between the short-size human ABCA8 and full-size human ABCA8 which has the two ATP-binding domains, remain unknown...
January 4, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29297778/chronic-cholestasis-is-associated-with-hypogonadism-and-premature-ovarian-failure-in-adult-rats-cholestasis-causes-ovarian-hypogonadism
#14
Yomna I Mahmoud
Hypogonadism is a well-known complication in males with chronic liver diseases. However, the consequences of chronic hepatopathies on female reproductive capacities have received relatively little attention. The present study evaluates the effect of chronic obstructive jaundice on the ovary of adult cycling rats. Estrous cyclicity was monitored to check the functional status of the hypothalamic-pituitary-ovarian axis. Ovarian changes were assessed using histomorphometric, immunohistochemical, and ultrastructural techniques...
January 2018: Ultrastructural Pathology
https://www.readbyqxmd.com/read/29287028/hbv-or-hcv-coinfection-in-hiv-1-infected-pregnant-women-in-france-prevalence-and-pregnancy-outcomes
#15
Valérie Benhammou, Roland Tubiana, Sophie Matheron, Pierre Sellier, Laurent Mandelbrot, Jérôme LE Chenadec, Emmanuelle Marel, Babak Khoshnood, Josiane Warszawski
BACKGROUND: Chronic HBV or HCV infection is frequent in HIV- infected persons but their impact on pregnant HIV-infected women is understudied. We explored whether these coinfections are associated with adverse pregnancy outcomes and lower response to antiretroviral therapy (ART). METHODS: Pregnancies in HIV-1-infected women included in the ANRS French Perinatal Cohort between 2005 and 2013 were analyzed if HBV and HCV infection statuses were available. RESULTS: Among 4236 women, the prevalence of HBV (HBs Ag+) and HCV (RNA+) were 6...
December 27, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29286519/comparative-characteristics-of-hepatoprotectors-used-for-the-treatment-of-non-alcoholic-steatohepatitis-associated-with-herpesvirus-infection-in-sufferers-of-the-chornobyl-accident
#16
O V Gasanova, E O Sarkisova, A A Chumak, L M Ovsyannikova, O V Nosach, L M Alohina, V A Gasanov, V V Kryzhanivska
Objective of the study was to determine the effectiveness of various groups of hepatoprotectors in the treatment of patients with nonalcoholic steatohepatitis (NASH) sufferers of the accident at the Chornobyl NPP following the assessment of metabolic changes and control of persistent infections. MATERIALS AND METHODS: The study included 104 males with NASH, who were sufferers of the Chornobyl disaster and underwent examination and treatment in the conditions of the clinics of the National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine...
December 2017: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/29286017/a-case-of-invasive-infection-caused-by-a-highly-virulent-strain-of-klebsiella-pneumoniae-displaying-hypermucoviscosity-in-a-patient-with-hepatic-involvement-without-liver-abscess
#17
Margherita Scapaticci, Marta Biscaro, Francesco Burelli, Lucio Cadamuro, Renzo Biscaro, Andrea Bartolini
Klebsiella pneumoniae is an opportunistic nosocomial pathogen belonging to the Enterobacteriaceae family that is associated with a wide range of infections. In the 1980s a new hypervirulent (hypermucoviscous) variant of Klebsiella pneumoniae (hvKP) emerged in southeast Asia and is now increasingly spreading to Western countries due to an invasive syndrome. hvKP isolates can cause serious, life-threatening community-acquired infections in younger healthy hosts, including liver abscess, pneumonia, meningitis and endophthalmitis...
December 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/29284646/a-drug-regimen-for-progressive-familial-cholestasis-type-2
#18
J Jeffrey Malatack, Daniel Doyle
Progressive familial cholestasis type 2 is caused by a genetically determined absence or reduction in the activity of the bile salt export pump (BSEP). Reduction or absence of BSEP activity causes a failure of bile salt excretion, leading to accumulation of bile salts in hepatocytes and subsequent hepatic damage. Clinically, patients are jaundiced, suffer from severe intractable pruritus, and evidence progressive liver dysfunction. A low level of serum γ-glutamyl transpeptidase, when associated with the described signs and symptoms, is often an early identifier of this condition...
December 28, 2017: Pediatrics
https://www.readbyqxmd.com/read/29278002/cholestasis-after-tips-placement-in-a-patient-with-primary-sclerosing-cholangitis-an-uncommon-complication
#19
Alejandro Salagre García, Carolina Muñoz Codoceo, Elena Gómez Domínguez, Inmaculada Fernández Vázquez, Gregorio Castellano Tortajada
We present the case of a patient with primary sclerosing cholangitis who presented a rapidly evolving cholestatic syndrome, with severe hyperbilirubinemia after placing a TIPS. It was resolved with a biliary prosthesis inserted by ERCP. To date, no similar cases have been described in the literature, as it is a rare complication and, on the other hand, the experience with TIPS in patients with PSC is limited. The causes of hyperbilirubinemia after TIPS placement are very varied and it is crucial to perform a differential diagnosis to establish an early treatment...
December 26, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29275233/synthesis-physicochemical-properties-and-biological-activity-of-bile-acids-3-glucuronides-novel-insights-into-bile-acid-signalling-and-detoxification
#20
Serena Mostarda, Daniela Passeri, Andrea Carotti, Bruno Cerra, Carolina Colliva, Tiziana Benicchi, Antonio Macchiarulo, Roberto Pellicciari, Antimo Gioiello
Glucuronidation is considered an important detoxification pathway of bile acids especially in cholestatic conditions. Glucuronides are less toxic than the parent free forms and are more easily excreted in urine. However, the pathophysiological significance of bile acid glucuronidation is still controversial and debated among the scientific community. Progress in this field has been strongly limited by the lack of appropriate methods for the preparation of pure glucuronides in the amount needed for biological and pharmacological studies...
December 11, 2017: European Journal of Medicinal Chemistry
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