DOCSLIB.ORG

Expression of Specific Hepatocyte and Cholangiocyte Transcription Factors

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Laboratory Investigation (2008) 88, 865–872 & 2008 USCAP, Inc All rights reserved 0023-6837/08 $30.00 Expression of specific hepatocyte and cholangiocyte transcription factors in human liver disease and embryonic development Pallavi B Limaye, Gabriela Alarco´n, Andrew L Walls, Michael A Nalesnik, George K Michalopoulos, Anthony J Demetris and Erin R Ochoa Transcription factors are major determinants of cell-specific gene expression in all cell types. Studies in rodent liver have shown that alterations in transcription factor expression determine lineage specification during fetal liver development and signify transdifferentiation of cells of the biliary compartment into ‘oval’ cells and eventually hepatocytes in adult liver. We examined the cellular localization of hepatocyte- or BEC-associated transcription factors in human fetal and adult liver and in diseases in which transdifferentiation between hepatocytes and biliary cells may play a role. In the normal adult human liver, hepatocyte nuclear factor (HNF)4a and HNF6 appeared exclusively in hepatocytes; HNF1b, HNF3a, and HNF3b were observed only in BEC. During fetal development both BEC and hepatocytes expressed HNF3a, HNF3b, and HNF6. HNF1a was expressed only in fetal hepatocytes. We further examined expression of transcription factors in massive hepatic necrosis and in specific types of chronic liver disease. Hepatocyte-associated transcription factors HNF4a and HNF6 also appeared in BEC in massive hepatic necrosis and chronic hepatitis C virus infection. Similarly, HNF3b that is expressed only in BEC in normal adult liver was also observed in hepatocytes in primary biliary cirrhosis and chronic biliary obstruction. These data mimic previous findings in rodents in which hepatocyte-associated transcription factors appear in biliary cells prior to emergence of oval cells, which function as progenitor cells for hepatocytes when the regenerative capacity of the latter is compromised. Laboratory Investigation (2008) 88, 865–872; doi:10.1038/labinvest.2008.56; published online 23 June 2008 KEYWORDS: transcription factors; embryonic human liver; transdifferentiation; hepatocytes; biliary epithelial cells Hepatocytes and biliary epithelial cells (BEC) are distinctly specific cell types, cells with promiscuous expression of both different cell types in the adult liver. In addition to trans- hepatocytic and BEC single-gene markers are often seen in cription factors expressed commonly in many cell types, chronic liver disease.3–7 The appearance of ‘marker genes’ there are transcription factors expressed (in the adult liver) from the other (hepatocyte or BEC) cell type suggests that a only in hepatocytes or BEC. Expression of transcription reprogramming in gene expression is taking place, as an factors is crucial in determining specificity of cell differ- adaptation to a specific pathobiologic or physiological chal- entiation. Cellular specificity in gene expression is in large lenge. Although the appearance of single-gene markers of part controlled by nuclear protein complexes, which include alternate specificity is well documented, changes in trans- transcription factors. The latter impart specificity to gene cription factors controlling in human liver have not been expression based on cell type. Thus, emergence of new characterized. transcription factors in fully differentiated cells transcends The regenerative capacities of hepatocytes and BEC have the appearance of mere single-gene markers and is inter- been tested in many experimental studies in rodents. In preted to signify large-scale reprogramming in gene expres- uncomplicated liver regeneration after partial hepatectomy or sion.1,2 Whereas in normal adult liver, the expression of during BEC proliferation following bile duct ligation, hepato- hepatocyte- or BEC-associated single genes is localized to the cytes or BEC respectively proliferate to generate more cells Department of Pathology, Division of Transplantation Pathology, Montefiore University Hospital, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Correspondence: Dr ER Ochoa, MD, Department of Pathology, Division of Transplantation Pathology, UPMC Montefiore, University of Pittsburgh School of Medicine, Suite E-739, 200 Lothrop Street, Pittsburgh, PA 15213-2582, USA. E-mail: [email protected] Received 29 January 2008; accepted 02 April 2008 www.laboratoryinvestigation.org | Laboratory Investigation | Volume 88 August 2008 865 Transcription factors in human liver disease PB Limaye et al of their type.8–10 If, however, the capacity of hepatocytes or mediate differentiation between hepatocytes and BEC. BEC to regenerate more of their own is impaired, then (in Structures containing hepatocytes, BEC and intermediate rodent systems) hepatocytes and BEC can transdifferentiate cell types were recently described in a ‘bipolar’ ductular into each other. BEC (from canals of Hering and/or portal reaction.4–6,32 The above studies have well documented the ductules) proliferate transiently to generate ‘oval’ cells which appearance of alternate single-gene markers in hepatic cells in undergo gradual morphologic and biochemical changes to different disease states. Expression of genes specific to cell become hepatocytes.11–15 Oval cells express both biliary- and types (markers) has always been used as basis for assessing hepatocyte-associated genes. There are two pieces of evidence differentiation status of a given cell. However, gene expres- supporting the biliary origin of the oval cells. In the first piece sion patterns (including cell-specific markers) in any cell type of evidence, oval cells do not appear when BEC are subjected are determined in large part by the expression of specific to lethal toxic injury prior to the induction of the oval cell transcription factors, which, in synergy with epigenetic protocol.16 The second piece of evidence is the appearance of changes, determine cell differentiation and define cell lineage. hepatocyte-associated transcription factors in BECs very Thus we investigated expression of hepatocyte- or BEC- soon after the initiation of the oval cell protocol.17 We have associated transcription factors in both hepatocytes and BEC also shown in rats that when the capacity of BEC to pro- in human liver, as a tool to determine initiation of liferate is impaired by delivering a toxic injury by DAPM, promiscuous altered gene expression patterns between more BEC can be formed by transdifferentiation of periportal hepatocytes and biliary cells during chronic liver disease, hepatocytes.18 comparable to the changes seen in impaired regeneration Hepatocytic and BEC lineage is specified in part by a set of models in rodents. specific liver-enriched transcription factors.1,2,19,20 Studies with knockout mice have shown that hepatocyte nuclear MATERIALS AND METHODS factor (HNF)1a and HNF4a regulate transcription of genes Case Selection essential for the hepatocytic cell lineage,21–23 whereas HNF1b With approval from the IRB of the University of Pittsburgh and HNF6 are involved in development of the gallbladder (IRB no. 0501051), paraffin-embedded liver sections were and bile ducts.24–26 Previous studies with rodents have shown obtained from the archives of the Department of Pathology, that the earliest step in the generation of the oval cells is the University of Pittsburgh Medical Center. Specimens appearance of hepatocyte-associated transcription factors in were obtained from five cases each of first, second, and BEC of portal ductules and canals of Hering.17,27 This is third trimester fetal liver tissue, and normal adult (NL). direct evidence of initiation of large-scale gene reprogram- Data presented in this article were collected from four ming, as transcription factors affect expression of multiple cases of end-stage cirrhosis from chronic HCV infection, genes associated with differentiation of specific cell types. In five cases of massive hepatic necrosis (causes included HBV this model, appearance of hepatocyte-associated transcrip- infection, autoimmune hepatitis, acetaminophen), five cases tion factors in biliary cells suggests initiation of expression of of chronic biliary obstruction (none of the cases included genes associated with hepatocyte differentiation in biliary cell pancreatic cancer), and three cases of late-stage PBC. types. This is perfectly consistent with the large-scale ex- The specimens related to specific liver diseases all represent pression of hepatocyte-associated genes in oval cells, as they end-stage liver disease in their type. They were obtained gradually transform to small and eventually regular hepato- from livers explanted for the purpose of orthotopic cytes in the AAF-hepatectomy protocol.11–13 liver transplantation. The normal adult liver tissue samples As most of the literature of expression of transcription were selected from liver specimens resected for metastatic factors in hepatic cell types derives from studies in rodents, colorectal carcinoma. we first assessed transcription factor expression in hepato- cytes versus BEC in human fetal and normal adult liver, to Immunohistochemistry provide a comparison standard with literature derived from Immunohistochemical localization studies of HNF1a, rodent-based experimental studies. We also examined the HNF1b, HNF3a, HNF3b, HNF4a, HNF6 were conducted on presence of specific transcription factors in liver diseases in formalin-fixed paraffin-embedded liver sections (4-mm which hepatocytes or biliary cells are selectively affected. thick). Corresponding
Recommended publications
  • Papilla with Separate Bile and Pancreatic Duct Orifices

    Papilla with Separate Bile and Pancreatic Duct Orifices

    JOP. J Pancreas (Online) 2013 May 10; 14(3):302-303. MULTIMEDIA ARTICLE – Clinical Imaging Papilla with Separate Bile and Pancreatic Duct Orifices Surinder Singh Rana, Deepak Kumar Bhasin Department of Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER). Chandigarh, India A 32-year-old male, a known case of alcohol related Conflict of interest The authors have no potential chronic non calcific pancreatitis, was referred to us for conflicts of interest pancreatic endotherapy for relief of intractable abdominal pain. The cross sectional imaging studies References had revealed an irregularly dilated main pancreatic duct. The examination of the major duodenal papilla 1. Silvis SE, Vennes JA, Dreyer M. Variation in the normal duodenal papilla. Gastrointest Endosc 1983; 29:132-133 [PMID; revealed the presence of two separate orifices at 6852473] endoscopic retrograde cholangiopancreatography (ERCP) (Image). The cranial orifice was located at 11- 12 clock position whereas the caudal orifice was located at 4-5 clock position. The caudal orifice was selectively cannulated and the injection of the contrast revealed presence of an irregularly dilated main pancreatic duct. The cannula and the guide wire introduced through the caudal orifice selectively entered the pancreatic duct and did not come out through the cranial orifice. During ERCP, bile could be seen coming out of the cranial orifice, confirming it to be the orifice of common bile duct. Following selective cannulation of the main pancreatic duct, a 5-Fr stent was placed into the pancreatic duct. Following this, the patient had complete pain relief and is planned for further sessions of pancreatic endotherapy along with pancreatic sphincterotomy.
  • Fact Sheet - Symptoms of Pancreatic Cancer

    Fact Sheet - Symptoms of Pancreatic Cancer

    Fact Sheet - Symptoms of Pancreatic Cancer Diagnosis Pancreatic cancer is often difficult to diagnose, because the pancreas lies deep in the abdomen, behind the stomach, so tumors are not felt during a physical exam. Pancreatic cancer is often called the “silent” cancer because the tumor can grow for many years before it causes pressure, pain, or other signs of illness. When symptoms do appear, they can vary depending on the size of the tumor and where it is located on the pancreas. For these reasons, the symptoms of pancreatic cancer are seldom recognized until the cancer has progressed to an advanced stage and often spread to other areas of the body. General Symptoms Pain The first symptom of pancreatic cancer is often pain, because the tumors invade nerve clusters. Pain can be felt in the stomach area and/or in the back. The pain is generally worse after eating and when lying down, and is sometimes relieved by bending forward. Pain is more common in cancers of the body and tail of the pancreas. The abdomen may also be generally tender or painful if the liver, pancreas or gall bladder are inflamed or enlarged. It is important to keep in mind that there are many other causes of abdominal and back pain! Jaundice More than half of pancreatic cancer sufferers have jaundice, a yellowing of the skin and whites of the eyes. Jaundice is caused by a build-up bilirubin, a substance which is made in the liver and a component of bile. Bilirubin contains a lot of yellow pigment, and gives bile it’s color.
  • Mft•] ~;;I~ [I) I~ T?L3 ·Ilr!F·S; [,J ~ M

    Mft•] ~;;I~ [I) I~ T?L3 ·Ilr!F·S; [,J ~ M

    Mft•] ~;;I~ [I) I~ t?l3 ·ilr!f·S; [,j ~ M Hepatobiliary Imaging Update Maggie Chester and Jerry Glowniak Veterans Affairs Medical Center and Oregon Health Sciences University, Portland, Oregon and the gallbladder ejection fraction (EF) after the injection This is the first article in a four-part series on interventional of cholecystokinin (CCK) (Kinevac®, Squibb Diagnostics, nuclear medicine. Upon completion, the nuclear medicine New Brunswick, NJ). A brief description of the hepatic ex­ technologist should be able to (1) list the advantages of using traction fraction (HEF) was given; the technique used quan­ interventional hepatic imaging, (2) identify the benefit in tifies hepatocyte function more accurately than does excretion calculating HEF, and (3) utilize the HEF calculation method when appropriate. half-time. Since publication of the previous article (5), the HEF has become more widely used as a measure of hepatocyte function, and nearly all the major nuclear medicine software vendors include programs for calculating the HEF. Scintigraphic assessment of hepatobiliary function began in In this article, we will describe new observations and meth­ the 1950s with the introduction of iodine-131 C31 1) Rose ods used in hepatobiliary imaging. The following topics will bengal (1). Due to the poor imaging characteristics of 1311, be discussed: ( 1) the use of morphine as an aid in the diagnosis numerous attempts were made to find a technetium-99m 99 of acute cholecystitis, (2) the rim sign in the diagnosis of acute ( mTc) labeled hepatobiliary agent (2). The most useful of cholecystitis, and (3) methods for calculating the HEF. the several 99mTc-labeled agents that were investigated were the iminodiacetic acid (IDA) analogs, which were introduced MORPHINE-AUGMENTED CHOLESCINTIGRAPHY in the mid 1970s (3).
  • Progress Report Cholestasis and Lesions of the Biliary Tract in Chronic Pancreatitis

    Progress Report Cholestasis and Lesions of the Biliary Tract in Chronic Pancreatitis

    Gut: first published as 10.1136/gut.19.9.851 on 1 September 1978. Downloaded from Gut, 1978, 19, 851-857 Progress report Cholestasis and lesions of the biliary tract in chronic pancreatitis The occurrence of jaundice in the course of chronic pancreatitis has been recognised since the 19th century" 2. But in the early papers it is uncertain whether the cases were due to acute, acute relapsing, or to chronic pan- creatitis, or even to pancreatic cancer associated with pancreatitis or benign ampullary stenosis. With the introduction of endoscopic retrograde cholangiopancreato- graphy (ERCP), there has been a renewed interest in the biliary complica- tions of chronic pancreatitis (CP). However, papers published recently by endoscopists have generally neglected the cholangiographic aspect of the lesions and are less precise and less well documented than papers published just after the second world war, following the introduction of manometric cholangiography3-5. Furthermore, the description of obstructive jaundice due to chronic pancreatitis, classical 20 years ago, seems to have been forgotten until the recent papers. Radiological aspects of bile ducts in chronic pancreatitis http://gut.bmj.com/ If one limits the subject to primary diseases of the pancreas, particularly chronic calcifying pancreatitis (CCP)6, excluding chronic pancreatitis secondary to benign ampullary stenosis7, cancer obstructing the main pancreatic duct8 9 and acute relapsing pancreatitis secondary to gallstones'0 radiological aspect of the main bile duct" is type I the most.common on September 25, 2021 by guest. Protected copyright. choledocus (Figure). This description has been repeatedly confirmed'2"13. It is a long stenosis of the intra- or retropancreatic part of the main bile duct.
  • Bile Duct Cancer Causes, Risk Factors, and Prevention Risk Factors

    Bile Duct Cancer Causes, Risk Factors, and Prevention Risk Factors

    cancer.org | 1.800.227.2345 Bile Duct Cancer Causes, Risk Factors, and Prevention Risk Factors A risk factor is anything that affects your chance of getting a disease such as cancer. Learn more about the risk factors for bile duct cancer. ● Bile Duct Risk Factors ● What Causes Bile Duct Cancer? Prevention There's no way to completely prevent cancer. But there are things you can do that might help lower your risk. Learn more. ● Can Bile Duct Cancer Be Prevented? Bile Duct Risk Factors A risk factor is anything that affects your chance of getting a disease like cancer. Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed. But having a risk factor, or even many risk factors, does not mean that a person will get 1 ____________________________________________________________________________________American Cancer Society cancer.org | 1.800.227.2345 the disease. And many people who get the disease have few or no known risk factors. Researchers have found some risk factors that make a person more likely to develop bile duct cancer. Certain diseases of the liver or bile ducts People who have chronic (long-standing) inflammation of the bile ducts have an increased risk of developing bile duct cancer. Certain conditions of the liver or bile ducts can cause this, these include: ● Primary sclerosing cholangitis (PSC), a condition in which inflammation of the bile ducts (cholangitis) leads to the formation of scar tissue (sclerosis). People with PSC have an increased risk of bile duct cancer.
  • Suppression of Hepatocyte CYP1A2 Expression by Kupffer Cells Via Ahr Pathway: the Central Role of Proinflammatory Cytokines

    Suppression of Hepatocyte CYP1A2 Expression by Kupffer Cells Via Ahr Pathway: the Central Role of Proinflammatory Cytokines

    339-346 29/6/06 12:40 Page 339 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE 18: 339-346, 2006 339 Suppression of hepatocyte CYP1A2 expression by Kupffer cells via AhR pathway: The central role of proinflammatory cytokines RONGQIAN WU1, XIAOXUAN CUI1, WEIFENG DONG1, MIAN ZHOU1, H. HANK SIMMS2 and PING WANG1 1Department of Surgery, North Shore University Hospital and Long Island Jewish Medical Center, Manhasset, NY 11030, USA Received February 6, 2006; Accepted March 23, 2006 Abstract. The hepatic cytochrome P-450 (CYP) enzyme such downregulation. Inhibition of proinflammatory cytokines system provides a major aspect of liver function, yet alterations by curcumin may provide a novel approach to modulate the of CYP in sepsis remain largely unknown. Although we have hepatic CYP function in sepsis. recently shown that CYP1A2, one of the major isoforms of CYP in rats, is downregulated in sepsis, the underlying mech- Introduction anism and possible therapeutic approaches warrant further investigation. The aim of this study was to determine whether Sepsis is the leading cause of death in non-cardiac intensive Kupffer cells (KCs) play any role in suppressing CYP1A2 in care units with >210,000 people succumbing to overwhelming the hepatocytes (HCs) and if so, how to modulate CYP1A2 infection (or the resultant multiple organ failure) in the US expression in sepsis. To study this, primary KCs and HCs annually (1). Although experimental studies using cell and were cultured separately or together with or without transwells. animal models have greatly improved our understanding of Cells and supernatant samples were collected after various the pathophysiology of sepsis, there remains a remarkable stimulations.
  • Hepatocyte Growth Factor Signaling Pathway As a Potential Target in Ductal Adenocarcinoma of the Pancreas

    Hepatocyte Growth Factor Signaling Pathway As a Potential Target in Ductal Adenocarcinoma of the Pancreas

    JOP. J Pancreas (Online) 2017 Nov 30; 18(6):448-457. REVIEW ARTICLE Hepatocyte Growth Factor Signaling Pathway as a Potential Target in Ductal Adenocarcinoma of the Pancreas Samra Gafarli, Ming Tian, Felix Rückert Department of Surgery, Medical Faculty Mannheim, University of Heidelberg, Germany ABSTRACT Hepatocyte growth factor is an important cellular signal pathway. The pathway regulates mitogenesis, morphogenesis, cell migration, invasiveness and survival. Hepatocyte growth factor acts through activation of tyrosine kinase receptor c-Met (mesenchymal epithelial transition factor) as the only known ligand. Despite the fact that hepatocyte growth factor is secreted only by mesenchymal origin cells, the targets of this multifunctional pathway are cells of mesenchymal as well as epithelial origin. Besides its physiological role recent evidences suggest that HGF/c-Met also plays a role in tumor pathophysiology. As a “scatter factor” hepatocyte growth factor stimulates cancer cell migration, invasion and subsequently promote metastases. Hepatocyte growth factor further is involved in desmoplastic reaction and consequently indorse chemo- and radiotherapy resistance. Explicitly, this pathway seems to mediate cancer cell aggressiveness and to correlate with poor prognosis and survival rate. Pancreatic Ductal Adenocarcinoma is a carcinoma with high aggressiveness and metastases rate. Latest insights show that the HGF/c-Met signal pathway might play an important role in pancreatic ductal adenocarcinoma pathophysiology. In the present review, we highlight the role of HGF/c-Met pathway in pancreatic ductal adenocarcinoma with focus on its effect on cellular pathophysiology and discuss its role as a potential therapeutic target in pancreatic ductal adenocarcinoma. INTRODUCTION activation causes auto-phosphorylation of c-Met and subsequent activation of downstream signaling pathways Hepatocyte growth factor (HGF) is a multifunctional such as mitogen-activated protein kinases (MAPKs), gene.
  • Hepatic Toxicity

    Hepatic Toxicity

    Hepatic Toxicity MSc in Molecular Pathology and Toxicology 2001 Andy Smith MRC Toxicology Unit THE LIVER • The liver constitutes about 5% of the body mass of a rodent or human. • It has many functions eg. Carbohydrate storage and metabolism Synthesis of fibrinogen and albumin etc. Fat metabolism Synthesis of bile acids Metabolism of hormones Formation of urea from amino acids • Blood supply is about 20% arterial-80% venous. • May contain 10-15% of blood volume INFLUENCE OF TOXIC CHEMICALS ON THE LIVER • The liver is the most common site of damage in laboratory animals administered drugs and other chemicals. There are many reasons including the fact that the liver is the first major organ to be exposed to ingested chemicals due to its portal blood supply. • Although chemicals are delivered to the liver to be metabolized and excreted, this can frequently lead to activation and liver injury. • Study of the liver has been and continues to be important in understanding fundamental molecular mechanisms of toxicity as well as in assessment of risks to humans. VENA CAVA HEPATIC VEIN LIVER HEPATIC PORTAL VEIN BILE DUCT SMALL AND LARGE INTESTINE LOBULE PORTAL VEIN BLOOD FLOW HEPATIC ARTERY III I BILE FLOW BILE DUCT CENTRAL VEIN PORTAL TRIAD TYPES OF LIVER CELLS Hepatocytes- Not all the same; depends on lobular site Zone I Higher in respiratory enzymes (periportal) Zone III Higher in cytochrome P450 (centrilobular) Endothelial cells Bile duct cells Oval cells- Possibly stem cells Kupffer cells- Phagocytic cells Important role in inflammation Ito cells- Fat storing or stellate cells TYPES OF HEPATIC INJURY OR RESPONSES Each of the different cell types may respond to a toxic insult.
  • Nomina Histologica Veterinaria, First Edition

    Nomina Histologica Veterinaria, First Edition

    NOMINA HISTOLOGICA VETERINARIA Submitted by the International Committee on Veterinary Histological Nomenclature (ICVHN) to the World Association of Veterinary Anatomists Published on the website of the World Association of Veterinary Anatomists www.wava-amav.org 2017 CONTENTS Introduction i Principles of term construction in N.H.V. iii Cytologia – Cytology 1 Textus epithelialis – Epithelial tissue 10 Textus connectivus – Connective tissue 13 Sanguis et Lympha – Blood and Lymph 17 Textus muscularis – Muscle tissue 19 Textus nervosus – Nerve tissue 20 Splanchnologia – Viscera 23 Systema digestorium – Digestive system 24 Systema respiratorium – Respiratory system 32 Systema urinarium – Urinary system 35 Organa genitalia masculina – Male genital system 38 Organa genitalia feminina – Female genital system 42 Systema endocrinum – Endocrine system 45 Systema cardiovasculare et lymphaticum [Angiologia] – Cardiovascular and lymphatic system 47 Systema nervosum – Nervous system 52 Receptores sensorii et Organa sensuum – Sensory receptors and Sense organs 58 Integumentum – Integument 64 INTRODUCTION The preparations leading to the publication of the present first edition of the Nomina Histologica Veterinaria has a long history spanning more than 50 years. Under the auspices of the World Association of Veterinary Anatomists (W.A.V.A.), the International Committee on Veterinary Anatomical Nomenclature (I.C.V.A.N.) appointed in Giessen, 1965, a Subcommittee on Histology and Embryology which started a working relation with the Subcommittee on Histology of the former International Anatomical Nomenclature Committee. In Mexico City, 1971, this Subcommittee presented a document entitled Nomina Histologica Veterinaria: A Working Draft as a basis for the continued work of the newly-appointed Subcommittee on Histological Nomenclature. This resulted in the editing of the Nomina Histologica Veterinaria: A Working Draft II (Toulouse, 1974), followed by preparations for publication of a Nomina Histologica Veterinaria.
  • Guideline for the Evaluation of Cholestatic Jaundice

    Guideline for the Evaluation of Cholestatic Jaundice

    CLINICAL GUIDELINES Guideline for the Evaluation of Cholestatic Jaundice in Infants: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition ÃRima Fawaz, yUlrich Baumann, zUdeme Ekong, §Bjo¨rn Fischler, jjNedim Hadzic, ôCara L. Mack, #Vale´rie A. McLin, ÃÃJean P. Molleston, yyEzequiel Neimark, zzVicky L. Ng, and §§Saul J. Karpen ABSTRACT Cholestatic jaundice in infancy affects approximately 1 in every 2500 term PREAMBLE infants and is infrequently recognized by primary providers in the setting of holestatic jaundice in infancy is an uncommon but poten- physiologic jaundice. Cholestatic jaundice is always pathologic and indicates tially serious problem that indicates hepatobiliary dysfunc- hepatobiliary dysfunction. Early detection by the primary care physician and tion.C Early detection of cholestatic jaundice by the primary care timely referrals to the pediatric gastroenterologist/hepatologist are important physician and timely, accurate diagnosis by the pediatric gastro- contributors to optimal treatment and prognosis. The most common causes of enterologist are important for successful treatment and an optimal cholestatic jaundice in the first months of life are biliary atresia (25%–40%) prognosis. The Cholestasis Guideline Committee consisted of 11 followed by an expanding list of monogenic disorders (25%), along with many members of 2 professional societies: the North American Society unknown or multifactorial (eg, parenteral nutrition-related) causes, each of for Gastroenterology, Hepatology and Nutrition, and the European which may have time-sensitive and distinct treatment plans. Thus, these Society for Gastroenterology, Hepatology and Nutrition. This guidelines can have an essential role for the evaluation of neonatal cholestasis committee has responded to a need in pediatrics and developed to optimize care.
  • Biliary Tract Cancer*

    Biliary Tract Cancer*

    Biliary Tract Cancer* What is Biliary Tract Cancer*? Let us answer some of your questions. * Cholangiocarcinoma (bile duct cancer) * Gallbladder cancer * Ampullary cancer ESMO Patient Guide Series based on the ESMO Clinical Practice Guidelines esmo.org Biliary tract cancer Biliary tract cancer* An ESMO guide for patients Patient information based on ESMO Clinical Practice Guidelines This guide has been prepared to help you, as well as your friends, family and caregivers, better understand biliary tract cancer and its treatment. It contains information on the causes of the disease and how it is diagnosed, up-to- date guidance on the types of treatments that may be available and any possible side effects of treatment. The medical information described in this document is based on the ESMO Clinical Practice Guideline for biliary tract cancer, which is designed to help clinicians with the diagnosis and management of biliary tract cancer. All ESMO Clinical Practice Guidelines are prepared and reviewed by leading experts using evidence gained from the latest clinical trials, research and expert opinion. The information included in this guide is not intended as a replacement for your doctor’s advice. Your doctor knows your full medical history and will help guide you regarding the best treatment for you. *Cholangiocarcinoma (bile duct cancer), gallbladder cancer and ampullary cancer. Words highlighted in colour are defined in the glossary at the end of the document. This guide has been developed and reviewed by: Representatives of the European
  • Cholangiocytes and the Environment in Primary Sclerosing Cholangitis

    Cholangiocytes and the Environment in Primary Sclerosing Cholangitis

    Gut Online First, published on July 21, 2017 as 10.1136/gutjnl-2017-314249 Leading article microbial infection (eg, Cryptosporidium Cholangiocytes and the environment in parvum)16 and PSC; (iii) accumulating evidence supporting a critical role for the Gut: first published as 10.1136/gutjnl-2017-314249 on 21 July 2017. Downloaded from primary sclerosing cholangitis: where is intestinal microbiome in the pathogenesis of PSC17; (iv) a similar genetic architecture the link? in PSC as in a prototypical exposure-driven autoimmune disease, coeliac disease18; and 1 2,3 1 (v) a similar genetic architecture in PSC as Steven P O’Hara, Tom H Karlsen, Nicholas F LaRusso 19 20 in cholestatic drug-induced injury. We began studying the cholangiopathy In primary sclerosing cholangitis (PSC), in medicine. Robert Koch in the late 19th in HIV-infected patients (a form of SSC annular fibrosis around intrahepatic and century proposed criteria to identify a due to biliary tract infection by opportu- extrahepatic bile ducts leads to progres- disease as infectious.9 These included nistic pathogens, including C parvum)21 sive liver disease for which there is no (i) the organism is regularly associated both because it was a significant clinical effective therapy except liver transplanta- with the disease, (ii) the organism can problem and as a result of our own clinical tion.1 The concentric accumulation of be isolated from the diseased host and experience with C parvum-induced SSC.22 connective tissue around bile ducts grown in culture and (iii) the disease To summarise key points from multiple suggests that the cholangiocyte plays an can be reproduced when the organism in vitro and in vivo studies,16 23 we found integral role in PSC pathogenesis.