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Cholestatic liver diseases

Kouichi Sakamoto, Ngin Cin Khai, Yuqing Wang, Rie Irie, Hideo Takamatsu, Hiroshi Matsufuji, Ken-Ichiro Kosai
In contrast to hepatocyte growth factor (HGF), the therapeutic potential and pathophysiologic roles of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in liver diseases remain relatively unknown. To address the lack of effective pharmacologic treatments for cholestatic liver injuries, as well as to clarify the biologic features of these growth factors, we explored the effects of HB-EGF and HGF in mice with cholestatic liver injury induced by bile duct ligation (BDL). The mice were assessed 3, 5 and/or 14 days after BDL (acute, subacute and/or chronic phases, respectively) and intravenous injection of adenoviral vector expressing LacZ (control), HB-EGF, HGF, or HB-EGF and HGF...
October 20, 2016: International Journal of Molecular Medicine
Jonathan G Stine, Jennifer Wang, Brian W Behm
Drug-induced liver injury is a rare but clinically important diagnosis. Vedolizumab is an α4β7 integrin inhibitor recently approved for use in patients with moderate-to-severe inflammatory bowel disease. Cases of hepatoxicity due to vedolizumab in the pre-marketing stage were rare, and all cases resolved upon drug withdrawal. We present here the first reported case of hepatotoxicity attributable to vedolizumab, which despite drug cessation persisted with chronic cholestatic liver injury.
September 28, 2016: Journal of Clinical and Translational Hepatology
Deniz Koksal, Aydin Seref Koksal, Ahmet Gurakar
Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic liver disease caused by diffuse inflammation, destruction and fibrosis of the intrahepatic bile ducts, ultimately leading to cirrhosis, portal hypertension and liver failure. The pathogenesis of PBC is incompletely understood, but current data suggest roles for genetic susceptibility and environmental factors. PBC is often thought of as an organ-specific autoimmune disease, which mainly targets the liver; however, lung tissue is also a site for autoimmune involvement of PBC...
September 28, 2016: Journal of Clinical and Translational Hepatology
Jillian Reardon, Trana Hussaini, Majid Alsahafi, Vladimir Marquez Azalgara, Siegfried R Erb, Nilufar Partovi, Eric M Yoshida
Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase...
September 28, 2016: Journal of Clinical and Translational Hepatology
Pierre Russo, John C Magee, Robert A Anders, Kevin E Bove, Catherine Chung, Oscar W Cummings, Milton J Finegold, Laura S Finn, Grace E Kim, Mark A Lovell, Margret S Magid, Hector Melin-Aldana, Sarangarajan Ranganathan, Bahig M Shehata, Larry L Wang, Frances V White, Zhen Chen, Catherine Spino
The liver biopsy guides diagnostic investigation and therapy in infants with undiagnosed cholestasis. Histologic features in the liver may also have prognostic value in the patient with biliary atresia (BA). We assessed the relative value of histologic features in 227 liver needle biopsies in discriminating between BA and other cholestatic disorders in infants enrolled in a prospective Childhood Liver Disease Research Network (ChiLDReN) cohort study by correlating histology with clinical findings in infants with and without BA...
October 21, 2016: American Journal of Surgical Pathology
Christoph R Werner, Verena Wagner, Bence Sipos, Maike Büttner-Herold, Kerstin Amann, Michael Haap, Nisar P Malek, Michael Bitzer, Ferruh Artunc
History and admission findings: We report on a 76-year-old man presenting with painless jaundice who developed dialysis-dependent acute kidney injury. Investigations: Biliary tract was examined with endoscopy, in addition kidney biopsy was performed. Diagnosis, treatment and course: A stenosing process could be seen in the biliary tract, leading to stent implantation. However, jaundice did not resolve. Kidney biopsy revealed bile casts indicating cholemic nephropathy. After switch of concomitant medication, hyperbilirubinemia resolved and kidney function was completely restored...
October 2016: Deutsche Medizinische Wochenschrift
Xiaojiaoyang Li, Zihang Yuan, Runping Liu, Hozeifa M Hassan, Hang Yang, Rong Sun, Luyong Zhang, Zhenzhou Jiang
Estrogen-induced cholestasis, known as intrahepatic cholestasis of pregnancy (ICP), is an estrogen-related liver disease that is widely recognized as female or pregnancy-specific. Our previous findings showed that the synthetic estrogen, 17α-ethinylestradiol (EE), induced cholestatic injury through ERK1/2-LKB1-AMP-activated protein kinase (AMPK) signaling pathway and its mediated suppression of farnesoid X receptor (FXR). To investigate the role played by bile acids in EE-induced cholestasis, we evaluated the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) on sandwich cultured rat primary hepatocytes (SCRHs) and an in vivo rat model...
October 12, 2016: Toxicology and Applied Pharmacology
M Gastaca, M Prieto, A Valdivieso, P Ruiz, A Ventoso, I Palomares, A Matarranz, L Martinez-Indart, J Ortiz de Urbina
OBJECTIVE: The aim of this study was to determine whether a portal flow of <1,000 mL/min in orthotopic liver transplantation (OLT) is associated with a higher incidence of early graft dysfunction (EGD) and graft loss. METHODS: A retrospective study was performed of 540 OLTs carried out consecutively from December 2004 to December 2013. Patients were divided into 2 groups: group A, portal flow <1,000 mL/min; and group B, portal flow >1,000 mL/min. We studied the incidence of EGD and graft survival...
September 2016: Transplantation Proceedings
Mi Na Gil, Du Ri Choi, Kwang Sik Yu, Ji Heun Jeong, Dong-Ho Bak, Do-Kyung Kim, Nam-Seob Lee, Je-Hun Lee, Young-Gil Jeong, Chun Soo Na, Dae Seung Na, Ki-Hyun Ryu, Seung Yun Han
Cholestatic liver cirrhosis (CLC) eventually proceeds to end-stage liver failure by mediating overwhelming deposition of collagen, which is produced by activated interstitial myofibroblasts. Although the beneficial effects of Rhus verniciflua Stokes (RVS) on various diseases are well-known, its therapeutic effect and possible underlying mechanism on interstitial fibrosis associated with CLC are not elucidated. This study was designed to assess the protective effects of RVS and its possible underlying mechanisms in rat models of CLC established by bile duct ligation (BDL)...
September 2016: Anatomy & Cell Biology
Bruno Baudin, Arnaud Bruneel, Raoul Poupon, Michel Vaubourdolle
Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease considered as an autoimmune disease. To identify new biomarkers of PBC, serum profiling analysis using Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was employed. Twelve patients with either asymptomatic PBC (group 1, n=6) or PBC with a poor response to UDCA (group 2, n=6), were compared to healthy controls (group 3, n=6). Analysing the 18 sera by using four SELDI-TOF arrays under various conditions, we found four biomarkers of PBC at 5...
October 1, 2016: Annales de Biologie Clinique
Ren-Jie Lu, Yan Zhang, Feng-Lei Tang, Zhong-Wei Zheng, Zheng-Da Fan, Shan-Mei Zhu, Xian-Feng Qian, Na-Na Liu
Drug-induced liver injury (DILI) is often undiagnosed or misdiagnosed clinically because of diagnostic difficulties caused by lack of laboratory-specific serological markers. In this study, we comprehensively assessed the clinical characteristics, laboratory indices, hepatotoxic drugs, risk factors and outcomes concerning DILI, and explored the similarities in mechanisms between Chinese and Western drug-induced DILI. Patients with a first diagnosis of DILI and a Roussel Uclaf Causality Assessment Method (RUCAM) score >3 points were enrolled for systematic retrospective study...
October 2016: Experimental and Therapeutic Medicine
Marta B Afonso, Pedro M Rodrigues, André L Simão, Dimitry Ofengeim, Tânia Carvalho, Joana D Amaral, Maria M Gaspar, Helena Cortez-Pinto, Rui E Castro, Junying Yuan, Cecília M P Rodrigues
Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3(-/-)) mice subjected to common bile duct ligation (BDL)...
2016: Cell Death & Disease
Lesley De Pietri, Marcello Bianchini, Gianluca Rompianesi, Elisabetta Bertellini, Bruno Begliomini
AIM: To describe the thromboelastography (TEG) "reference" values within a population of liver transplant (LT) candidates that underline the differences from healthy patients. METHODS: Between 2000 and 2013, 261 liver transplant patients with a model for end-stage liver disease (MELD) score between 15 and 40 were studied. In particular the adult patients (aged 18-70 years) underwent to a first LT with a MELD score between 15 and 40 were included, while all patients with acute liver failure, congenital bleeding disorders, and anticoagulant and/or antiplatelet drug use were excluded...
September 24, 2016: World Journal of Transplantation
Victor Navarro, Ikhlas Khan, Einar Björnsson, Leonard B Seeff, Jose Serrano, Jay H Hoofnagle
Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide and HDS induced liver injury in the U.S. has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data...
September 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Jun Yang, Ya-Li Yu, Yu Jin, Ying Zhang, Chang-Qing Zheng
AIM: To summarize and compare the clinical characteristics of drug-induced liver injury (DILI) and primary biliary cirrhosis (PBC). METHODS: A total of 124 patients with DILI and 116 patients with PBC treated at Shengjing Hospital Affiliated to China Medical University from 2005 to 2013 were included. Demographic data (sex and age), biochemical indexes (total protein, albumin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, and gamma glutamyltransferase), immunological indexes [immunoglobulin (Ig) A, IgG, IgM, antinuclear antibody, anti-smooth muscle antibody, anti-mitochondrial antibody, and anti-mitochondrial antibodies] and pathological findings were compared in PBC patients, untyped DILI patients and patients with different types of DILI (hepatocellular type, cholestatic type and mixed type)...
September 7, 2016: World Journal of Gastroenterology: WJG
Tomohiro Katsumi, Masashi Ninomiya, Taketo Nishina, Kei Mizuno, Kyoko Tomita, Hiroaki Haga, Kazuo Okumoto, Takafumi Saito, Tooru Shimosegawa, Yoshiyuki Ueno
Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease characterized pathologically by destruction of intrahepatic bile ducts. PBC is largely classified into three subtypes based on clinical course: (i) gradually progressive, (ii) portal hypertension, and (iii) hepatic failure. Previous studies have indicated that serum levels of the pro-inflammatory cytokine TNF-α, is elevated in PBC patients with fibrosis. Although the severity of cholangitis might also be related to the PBC subtype, its etiology has been unclear...
September 26, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Maya Balakrishnan, Fernanda Souza, Carolina Muñoz, Salvador Augustin, Nicole Loo, Yanhong Deng, Maria Ciarleglio, Guadalupe Garcia-Tsao
OBJECTIVES: Measurements of liver stiffness and spleen stiffness are useful noninvasive ways to assess fibrosis and portal hypertension in patients with chronic liver disease. One method for assessing stiffness is by point shear wave elastography via acoustic radiation force impulse imaging (ARFI). Its advantage is that sites where stiffness is measured are visualized sonographically. However, its reliability has not been well established, and all studies done to date evaluating the use of ARFI in chronic liver disease have been performed outside the United States...
September 23, 2016: Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine
Einar S Björnsson, Jiezhun Gu, David E Kleiner, Naga Chalasani, Paul H Hayashi, Jay H Hoofnagle
OBJECTIVE: The objective of the study was to define the clinical, biochemical, and histologic features of liver injury from thiopurines. BACKGROUND: Azathioprine (Aza) and 6-mercaptopurine (6-MP) can cause liver injury, but no large series exist. METHODS: Clinical and laboratory data and 6-month outcomes of patients with thiopurine hepatotoxicity from the Drug-Induced Liver Injury Network Prospective Study were analyzed. RESULTS: Twenty-two patients were identified, 12 due to Aza and 10 due to 6-MP, with a median age of 55 years; the majority were female (68%)...
June 14, 2016: Journal of Clinical Gastroenterology
Anna Cieślak, Isabelle Kelly, Jocelyn Trottier, Mélanie Verreault, Ewa Wunsch, Piotr Milkiewicz, Guy Poirier, Arnaud Droit, Olivier Barbier
This study aimed at establishing a sensitive multiple reaction monitoring-mass spectrometry (MRM-MS) method for the quantification of the drug metabolizing cytochrome P450 (CYP)3A4 enzyme in human liver homogenates. Liver samples were subjected to trypsin digestion. MRM-MS analyses were performed using three transitions optimized on one purified synthetic peptide unique to CYP3A4 and the standardizing protein, calnexin. Coefficient of variations for the precision and reproducibility of the MRM-MS measurement were also determined...
September 16, 2016: Proteomics
Jijing Tian, Guoxiang Yang, Huan-Yuan Chen, Daniel K Hsu, Alexey Tomilov, Kristin A Olson, Ali Dehnad, Sarah R Fish, Gino Cortopassi, Bin Zhao, Fu-Tong Liu, M Eric Gershwin, Natalie J Török, Joy X Jiang
Macrophage activation is an important feature of primary biliary cholangitis (PBC) pathogenesis and other cholestatic liver diseases. Galectin-3 (Gal3), a pleiotropic lectin, is produced by monocytic cells and macrophages. However, its role in PBC has not been addressed. We hypothesized that Gal3 is a key to induce NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in macrophages and in turn to propagate proinflammatory IL-17 signaling. In liver tissues from patients with PBC and dnTGF-βRII mice, a model of autoimmune cholangitis, the expression of Gal3, NLRP3, and the adaptor protein adaptor apoptosis-associated speck-like protein was induced, with the downstream activation of caspase-1 and IL-1β...
September 14, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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