DOCSLIB.ORG

Standardising the Interpretation of Liver Biopsies in Non‐Alcoholic Fatty

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Standardising the Interpretation of Liver Biopsies in Non‐Alcoholic Fatty DR RISH K PAI (Orcid ID : 0000-0002-1788-475X) MRS CLAIRE PARKER (Orcid ID : 0000-0002-8587-5441) DR BRIAN G FEAGAN (Orcid ID : 0000-0002-6914-3822) DR ROHIT LOOMBA (Orcid ID : 0000-0002-4845-9991) DR VIPUL JAIRATH (Orcid ID : 0000-0002-1092-0033) Article type : Original Scientific Paper TITLE: Standardizing the interpretation of liver biopsies in non-alcoholic fatty liver disease clinical trials SHORT TITLE: Interpretation of liver biopsies in NAFLD trials AUTHORS: Rish K. Pai1, David E. Kleiner2, John Hart3, Oyedele A. Adeyi4, Andrew D. Clouston5, Cynthia A. Behling6, Dhanpat Jain7, Sanjay Kakar8, Mayur Brahmania9, Lawrence Burgart10, Kenneth P. Batts11, Mark A. Valasek12, Michael S. Torbenson13, Maha Guindi14, Hanlin L. Wang15, Veeral Ajmera16, Leon A. Adams17, Claire E. Parker18, Brian G. Feagan19, Rohit Loomba20, Vipul Jairath21 AUTHOR AFFILIATIONS: 1Scottsdale, AZ, USA; 2Bethesda, MD, USA; 3Chicago, IL, USA; 4Toronto, ON, Canada; 5Brisbane, QLD, Australia; 6San Diego, CA, USA; 7New Haven, CT, This is the author manuscript accepted for publication and has undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may Author Manuscript lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/APT.15503 This article is protected by copyright. All rights reserved 2 USA; 8San Francisco, CA, USA; 9London, ON, Canada; 10Minneapolis, MN, USA; 11Minneapolis, MN, USA; 12La Jolla, CA, USA; 13Rochester, MN, USA; 14Los Angeles, CA, USA; 15Los Angeles, CA, USA; 16La Jolla, CA, USA; 17Perth, WA, Australia; 18London, ON, Canada; 19London, ON, Canada; 20La Jolla, CA, USA; 21London, ON, Canada. WORD COUNT: 3634 CORRESPONDENCE: Dr. Rish K. Pai, Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, 13400 E. Shea Blvd, Scottsdale, AZ, 85259; Phone: 480-301-4081; Fax: 480-301-9158; E-mail: [email protected] LIST OF ABBREVIATIONS: NASH-CRN, NASH Clinical Research Network; NAS, NAFLD activity score, NAS; SAF score, Steatosis, Activity, Fibrosis score. SUMMARY Background: There is substantial variation in how histologic definitions and scoring systems of non-alcoholic fatty liver disease are operationalized. Aims: Our objective was to develop a consensus-based framework for standardizing histologic assessment of liver biopsies in clinical trials of non-alcoholic fatty liver disease. Methods: An expert panel of 14 liver pathologists and 3 hepatologists was assembled. Using modified RAND/University of California Los Angeles appropriateness methodology, 130 items derived from literature review and expert opinion were rated by each panel member on a 1 to 9 scale. Disagreement was defined as > 5 ratings in the lowest (1-3) and highest (7-9) categories. Items were classified as inappropriate (median 1-3.5 without disagreement), uncertain (median 3.5-6.5 or any median with disagreement) or appropriate (median 6.5-9 without disagreement). Survey results were discussed as a group before voting. Results: Current measures of disease activity and fibrosis may not fully capture important features of non-alcoholic steatohepatitis. It was determined that alternative methods to evaluate Author Manuscript ballooning degeneration are needed, however panellists were uncertain whether portal inflammation, degree of steatosis, and Mallory-Denk bodies are important measures of disease activity. Furthermore, it was felt that current staging systems do not capture the full spectrum of This article is protected by copyright. All rights reserved 3 fibrosis in non-alcoholic steatohepatitis. A consensus definition and sub-stages for bridging fibrosis are needed. The severity of perisinusoidal fibrosis should be captured at all stages. Lastly, a method to evaluate features of fibrosis regression should be developed. Conclusion: The operating properties of the modifications proposed should be evaluated prospectively to determine reliability and responsiveness. KEYWORDS: Steatohepatitis, fibrosis, steatosis, ballooning degeneration, histopathology SUMMARY WORD COUNT: 250 INTRODUCTION Defined as evidence of hepatic steatosis in the absence of secondary causes of fat accumulation in the liver, 1 non-alcoholic fatty liver disease affects approximately one-quarter of adults worldwide and it is estimated that disease-related complications are increasing.2-4 Non- alcoholic fatty liver disease describes a spectrum of liver disease ranging from steatosis without hepatocyte injury (non-alcoholic fatty liver) to non-alcoholic steatohepatitis, which is characterized by steatosis coupled with inflammation and hepatocellular ballooning.5,6 Patients with non-alcoholic steatohepatitis have an increased risk of liver-related mortality and developing cirrhosis compared to those with non-alcoholic fatty liver.7 In the absence of effective medical treatment, it is anticipated that cirrhosis due to non-alcoholic steatohepatitis will become the leading worldwide cause for liver transplantation in the next decade.8,9 At present, there are no therapies approved by the U.S. Food and Drug Administration or the European Medicines Agency for the treatment of non-alcoholic steatohepatitis. However, several drugs are in early- or late-stage evaluation. Efficient development of new treatments for non- alcoholic steatohepatitis requires the use of objective measures of disease activity that are valid, reliable and responsive.10 While exploratory blood-based and imaging pharmacodynamic biomarkers have been 11 proposed, liver Author Manuscript biopsy remains the current gold standard for assessment of non-alcoholic fatty liver disease activity and fibrosis in clinical trials. Although fibrosis is not required for a diagnosis of non-alcoholic steatohepatitis, it is commonly present. Several histologic scoring systems for measuring microscopic disease activity and fibrosis exist. In 1999, Brunt et al. This article is protected by copyright. All rights reserved 4 developed a descriptive grading system for non-alcoholic steatohepatitis that separately grades necro-inflammatory activity and stages the extent of fibrosis.12 In 2003, Harrison et al. proposed a modification to the Brunt criteria to enable quantification of disease activity in a randomized controlled trial.13 The Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) proposed a system for scoring the full spectrum of non-alcoholic fatty liver disease lesions in 2005.14 The non-alcoholic fatty liver disease activity score (NAS) is an unweighted index calculated by summing component scores for items considered potentially reversible in the short term, namely, steatosis, lobular inflammation, and hepatocyte ballooning. This system also separately evaluates fibrosis. The NAS is the most commonly used index in non-alcoholic steatohepatitis clinical trials although few studies have formally evaluated the operating properties of the NAS outside of the NASH-CRN.14-16 In 2011, Younossi et al. correlated various histologic features with liver-related mortality.17 While this comprehensive pathologic evaluation demonstrated strong correlation between fibrosis and liver-related mortality, its validity for use in clinical trials is unknown. Finally, in 2012, Bedossa et al. described the Steatosis, Activity, Fibrosis (SAF) scoring system to facilitate the classification of liver biopsies taken from morbidly obese patients.18 In this study, an algorithm based on the steatosis and activity scores was proposed to aid in distinguishing between non-alcoholic fatty liver and non-alcoholic steatohepatitis. In late 2018, the U.S. Food and Drug Administration published draft guidance for industry regarding the development of therapies in non-cirrhotic patients with non-alcoholic steatohepatitis.19 Histologic evaluation is regarded as essential for determining therapeutic efficacy and determining phase IIb and III trial eligibility. Specifically, a NAS score greater than or equal to 4 with ballooning and lobular inflammation subscores of at least 1, in addition to a NASH-CRN fibrosis stage score of 2 or 3, are the recommended inclusion criteria. Three histologic endpoints have been proposed, including 1) resolution of steatohepatitis (defined by the U.S. Food and Drug Administration as a NAS lobular inflammation subscore ≤ 1, a ballooning subscore of 0, and any steatosis subscore), 2) improvement in liver fibrosis (defined as a reduction in NASH-CRNAuthor Manuscript fibrosis stage ≥ 1 and no worsening of steatohepatitis), and 3) resolution of steatohepatitis and improvement in fibrosis. Given the essential role of histopathology in determining the efficacy of new therapeutic agents for non-alcoholic steatohepatitis, we assembled a multidisciplinary panel of 17 liver This article is protected by copyright. All rights reserved 5 pathologists and hepatologists and conducted a two-round consensus process regarding the histologic assessment of liver biopsies in clinical trials using modified RAND/University of California Los Angeles appropriateness methodology.20 Factors that may lead to suboptimal evaluation of key outcome measures, and false negative trial results, were identified by the group. Standardizing the histologic assessment of liver biopsies in an effort to reduce variability and improve responsiveness has important implications for the large and increasing number of patients with non-alcoholic fatty liver disease participating in clinical trials and being managed in clinical practice. MATERIALS AND METHODS Item generation
Load more

Recommended publications
  • Review Article Alcohol Induced Liver Disease
    J Clin Pathol: first published as 10.1136/jcp.37.7.721 on 1 July 1984. Downloaded from J Clin Pathol 1984;37:721-733 Review article Alcohol induced liver disease KA FLEMING, JO'D McGEE From the University of Oxford, Nuffield Department ofPathology, John Radcliffe Hospital, Oxford OX3 9DU, England SUMMARY Alcohol induces a variety of changes in the liver: fatty change, hepatitis, fibrosis, and cirrhosis. The histopathological appearances of these conditions are discussed, with special atten- tion to differential diagnosis. Many forms of alcoholic liver disease are associated with Mallory body formation and fibrosis. Mallory bodies are formed, at least in part, from intermediate filaments. Associated changes in intermediate filament organisation in alcoholic liver disease also occur. Their significance in the pathogenesis of hepatocyte death may be related to abnormalities in messenger RNA function. The mechanisms underlying hepatic fibrogenesis are also discussed. Although alcohol has many effects on the liver, all formed after some period of alcohol abstinence, except cirrhosis are potentially reversible on cessa- alcohol related changes may not be seen. Accord- tion of alcohol ingestion. Cirrhosis is irreversible ingly, we shall consider the morphological changes and usually ultimately fatal. It is therefore important associated with alcohol abuse under the headings in to determine what factors are responsible for Table 1. development of alcohol induced cirrhosis, especially In the second part, the pathogenesis of alcohol since only 17-30% of all alcoholics become' cirrho- induced liver disease will be discussed, but this will tic.' This is of some urgency now, since there has deal only with the induction of alcoholic hepatitis, been an explosive increase in alcohol consumption fibrosis, and cirrhosis-that is, chronic alcoholic http://jcp.bmj.com/ in the Western World, particularly affecting young liver disease-and not with fatty change, for two people, resulting in a dramatic increase in the inci- reasons.
    [Show full text]
  • Fructose Diets on the Liver of Male Albino Rat and the Proposed Underlying Mechanisms S.M
    Folia Morphol. Vol. 78, No. 1, pp. 124–136 DOI: 10.5603/FM.a2018.0063 O R I G I N A L A R T I C L E Copyright © 2019 Via Medica ISSN 0015–5659 journals.viamedica.pl The differential effects of high-fat and high- -fructose diets on the liver of male albino rat and the proposed underlying mechanisms S.M. Zaki1, 2, S.A. Fattah1, D.S. Hassan1 1Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt 2Fakeeh College for Medical Sciences, Jeddah, Saudi Arabia [Received: 23 May 2108; Accepted: 26 June 2018] Background: The Western-style diet is characterised by the high intake of energy- -dense foods. Consumption of either high-fructose diet or saturated fat resulted in the development of metabolic syndrome. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. Many researchers studied the effect of high-fat diet (HFD), high-fructose diet (HFruD) and high-fructose high-fat diet (HFHF) on the liver. The missing data are the comparison effect of these groups i.e. are effects of the HFHF diet on the liver more pronounced? So, this study was designed to compare the metabolic and histopathological effect of the HFD, HFruD, and HFHF on the liver. The proposed underlying mechanisms involved in these changes were also studied. Materials and methods: Twenty four rats were divided into four groups: con- trol, HFD, HFruD, and HFHF. Food was offered for 6 weeks. Biochemical, light microscopic, immunohistochemical (Inducible nitric oxide synthase [iNOS] and alpha-smooth muscle actin [α-SMA]), real-time polymerase chain reaction (gene expression of TNF-α, interleukin-6, Bax, BCL-2, and caspase 3), histomorphometric analysis and oxidative/antioxidative markers (thiobarbituric acid reactive substances [TBARS], malondialdehyde [MDA]/glutathione [GSH] and superoxide dismutase [SOD]) were done.
    [Show full text]
  • The Morphology of Cirrhosis' Recommendations on Definition, Nomenclature, and Classification by a Working Group Sponsored by the World Health Organization
    J Clin Pathol: first published as 10.1136/jcp.31.5.395 on 1 May 1978. Downloaded from Journal of Clinical Pathology, 1978, 31, 395-414 The morphology of cirrhosis' Recommendations on definition, nomenclature, and classification by a working group sponsored by the World Health Organization P. P. ANTHONY, K. G. ISHAK, N. C. NAYAK, H. E. POULSEN, P. J. SCHEUER, AND L. H. SOBIN From the Bland-Sutton Institute ofPathology, Middlesex Hospital Medical School, London, the Armed Forces Institute ofPathology, Washington, the All India Institute ofMedical Sciences, New Delhi, Hvidovre Hospital, University of Copenhagen, The Royal Free Hospital School ofMedicine, London, and the Cancer Unit of the World Health Organization, Geneva SUMMARY This memorandum provides guidelines on the definition, nomenclature, and classification of cirrhosis, chronic hepatitis, and hepatic fibrosis. These are considered according to morphological characteristics and aetiology. It is hoped that this system will serve as a standard for diagnostic, research, and epidemiological purposes. The relationship of cirrhosis to liver cell carcinoma is briefly discussed and the possible morphological markers of an increased risk of malignancy are defined. The aim of this paper is to provide guidelines for the morphological terms but, in spite of many attempts, pathologist on the definition, nomenclature, and no single definition exists that does not require classification of hepatic cirrhosis and related con- further elaboration or qualification. The essential ditions. The many systems of classification in current features are considered to be parenchymal necrosis, http://jcp.bmj.com/ use (Table 1) hinder rather than help comparisons of regeneration, and diffuse fibrosis, resulting in dis- published data and the evaluation of relationships organisation of the lobular architecture throughout between cirrhosis and liver cancer.
    [Show full text]
  • Histopathologic Diagnosis of Chronic Viral Hepatitis
    Marmara Medical Journal 2016; 29 (Special issue 1): 18-28 DOI: 10.5472/MMJsi.2901.05 REVIEW / DERLEME Histopathologic diagnosis of chronic viral hepatitis Kronik viral hepatitin histopatolojik tanısı Çiğdem ATAİZİ ÇELİKEL ABSTRACT ÖZ Morphological evaluation of the liver continues to play a central Kronik viral hepatit tanısı, derecelendirme ve evreleme açısından, role for the diagnosis, grading and staging of chronic viral hepatitis. karaciğerin morfolojik değerlendirmesi önem taşır. Tanımsal The defining morphology is necroinflammation, that is hepatocyte morfoloji hepatosit hasarı ve inflamasyon ile karakterize injury and inflammation. Hepatocyte injury is usually irreversible, nekroinflamasyondur. Hepatosit hasarı, apoptoz ve/veya nekroz and presents as apoptosis and/or necrosis. Mononuclear cell şeklinde olup, genellikle geri dönüşümsüzdür. Portal alanda infiltration of the portal tracts, that is usually accompanied by mononükleer hücre infiltrasyonuna, çoğu zaman periportal periportal (interface) and lobular inflammation is typical. Continued (interfaz) ve lobüler inflamasyon eşlik eder. İnterfazda periportal necroinflammatory activity at the limiting plate destroying hepatositlerde süregelen hasar fibrogenezi tetikler ve siroz periportal parenchyma initiates fibrogenesis leading to cirrhosis. gelişebilir. Tamir dokusunun parçalanması, bozulan vaskülatürün Fibrosis can be reversible with fragmentation of scar tissue, organizasyonu ve hepatosit rejenerasyonu ile fibrozis/siroz resolving vascular derangements and parenchymal regeneration.
    [Show full text]
  • Chronic-Binge Model of Alcoholic Hepatitis in Long Evans Rats
    Ashdin Publishing Journal of Drug and Alcohol Research ASHDIN Vol. 3 (2014), Article ID 235837, 10 pages publishing doi:10.4303/jdar/235837 Research Article Chronic-Binge Model of Alcoholic Hepatitis in Long Evans Rats Teresa Ramirez,1 Ming Tong,2 and Suzanne M. de la Monte3 1Division of Gastroenterology and Liver Research Center, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA 2Department of Medicine, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA 3Departments of Medicine, Pathology, Neurology, and Neurosurgery, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA Address correspondence to Suzanne M. de la Monte, suzanne delamonte [email protected] Received 22 November 2013; Revised 8 May 2014; Accepted 2 June 2014 Copyright © 2014 Teresa Ramirez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background. Alcoholic hepatitis (AH) is largely a liver disease (ALD) that culminates in cirrhosis and liver histopathologic diagnosis that is based upon the presence of failure [26]. The major cause of ALD is heavy drinking over significant inflammation, hepatocellular lipid accumulation, ballooned prolonged periods [37]. degeneration of hepatocytes, and Mallory-Denk bodies. Underlying biochemical and molecular abnormalities
    [Show full text]
  • Viral Hepatitis (I)
    Viral Hepatitis (I) Luigi Terracciano Department of Pathology University Hospital Basel Basel, 19. 04. 2016 Definition Hepatitis means inflammation of the liver characterized by a variable combination of : • mononuclear inflammation (lymphocytes and plasma cells) • hepatocellular necrosis/apoptosis • hepatocellular regeneration Viral Hepatitis Unless otherwise specified, the term "viral hepatitis" is reserved for infection of the liver caused by a group of viruses having a particular affinity for the liver Systemic viral infections that can involve the liver include: 1.infectious mononucleosis (Epstein-Barr virus), which may cause a mild hepatitis during the acute phase; 2.cytomegalovirus, particularly in the newborn or immunosuppressed patient; 3.yellow fever, which has been a major and serious cause of hepatitis in tropical countries. Hepatotropic viruses cause overlapping patterns of disease Viral Hepatitis The Hepatitis Viruses Hepatitis A Virus Hepatitis B Virus Hepatitis C Virus Hepatitis D Virus Hepatitis E Agent Icosahedral capsid, Enveloped dsDNA Enveloped ssRNA Enveloped ssRNA Unenveloped ssRNA ssRNA Transmission Fecal-oral Parenteral; close contact Parenteral; close contact Parenteral; Waterborne close contact Incubation Period 2-6 wk 4-26 wk 2-26 wk 4-7 wk 2-8 wk Carrier state None 0.1-1.0% of blood donors 0.2-1.0% of blood donors. 1-10% in drug addicts Unknown in U.S. and Western worldi in U.S and Western world and hemophiliacs 1-2% of blood donors Chronic hepatitis None 5-10% of >50% <5% coinfection, None / Very rare acute
    [Show full text]
  • Obada Froukh and Sarah Basel Maha Shomaf
    9 Obada Froukh and Sarah Basel Obada Froukh Nasser M.Abdelqader Maha Shomaf 1 | P a g e Liver pathology Diseases of the liver are related to loss of its functions. Functions of the liver: 1-Metabolic: metabolism of different substances. 2-Synthetic: Albumin, clotting factors… If there is a Liver dysfunction, less albumin will be synthesized, and as you know albumin is the main plasma protein that generates the oncotic pressure causing fluid to go back from the interstitial fluid to the blood, decreasing the amount of albumin will cause edema. 3-Detoxification: Drugs, hormones, NH3. Most of drugs are detoxified in the liver, some of them exhibit side effects on it. (You should always ask the patients about their history regarding drugs). 4-Storage: Glycogen, TG—Triacylglycerides (fat), Fe, Cu, vitamins. 5-Excretory: Bile (which contains bilirubin from the metabolism of the heme). ❖ Features of the liver ✓ Normal weight of the liver is about 1.5 kg (2.5% of body weight). Increased liver weight is associated with many diseases. ✓ Blood supply of the liver: 1-Portal vein: 60 - 70%. 2-Hepatic artery: 30- 40%. Blood that is coming from the portal vein is not oxygenated but is filled with nutrients and other stuff coming from the gut in which hepatocytes are required to metabolize. On the other hand, blood that is coming from the hepatic artery is oxygenated. They both get mixed in the sinusoidal system of the liver; the hepatocytes do their action on the blood in the sinusoids, after that, blood is discharged to the three hepatic veins draining in the inferior vena cava.
    [Show full text]
  • Conference 5 8 October 2008
    The Armed Forces Institute of Pathology Department of Veterinary Pathology Conference Coordinator: Todd M. Bell, DVM WEDNESDAY SLIDE CONFERENCE 2008-2009 Conference 5 8 October 2008 Conference Moderator: Marc E. Mattix, DVM, MSS, Diplomate ACVP CASE I – Case HN 2516 (AFIP 3105584) neuronophagia of nerve cells, and minute malacic foci. The karyorrhexis of glial cells and rod cells were also Signalment: Whooper swan, Cygnus cygnus sparsely distributed throughout the CNS. The nuclei of perivascular cells (pericytes and astrocytes) were History: This wild swan was found dead at the northern sometimes swollen, and perivascular inflammatory cell lake of Japan in May, 2008. The local veterinarian found infiltration was indiscernible. the feces of this bird were influenza virus positive using a convenient test kit. The carcass was transported to our Imunohistochemistry using rabbit polyclonal antibody university and dissected within our P3 facility. against highly pathogenic avian influenza virus of H5N2 subtype as primary antibody revealed viral antigens in the Gross Pathology: Diffusely the lungs showed severe nuclei of astrocytes (arrow head in Fig. 1-2 and 1-3), congestive edema with edematous thickening of the pleura. microglial cells (arrows in Fig. 1-2), and nerve cells Petechial hemorrhages were scattered on the pericardium (arrows in Fig. 1-3) within and around the glial nodules. and pancreas. Pericardial fluid was mildly increased and accompanied mild edematous thickening of pericardium Besides the brain, lymphocytic necrosis in the spleen, and cardiac sac. The brain was congested. mild fibrinous bronchopneumonia and focal necrosis of exocrine pancreas were found with viral antigens in Laboratory Results: Highly pathogenic avian influenza alveolar epithelial cells, bronchial epithelial cells and virus of H5N1 subtype was isolated from the brain, lungs, exocrine pancreatic cells.
    [Show full text]
  • Of Cytochrome P450
    TMA.PED Lot No. 1810266 Tissue Microarray – Pediatric 3 mm diameter cores, 4 µm thick, 25 cases, 5 controls 01 02 03 04 05 06 A B C D E The microarray is provided unstained. The image above is a hematoxylin and eosin staining of the microarray, which was generated to illustrate histological characteristics of individual samples. This is a representative image. Store at 2-4°C for up to 3 months after date of receipt CAUTION: This sample should be considered as a potential biohazard and universal precautions should be followed. Intended for in vitro use only. These data were generated by and are the property of Sekisui XenoTech. These data are not to be reproduced, published or distributed without the express written consent of Sekisui XenoTech. Datasheet prepared 31 January 2019 TMA.PED Lot No. 1810266 Donor Information Alcohol Core Donor Pathology Gender Age Ethnicity BMI Consumption A01 H1393 Very near normal Male 4 months C 18.8 None A02 H0395 Hepatocyte degeneration 15-20% Male 5.5 months C 17.3 None A03 H1383 Normal Male 12 months C 19.7 None A04 H0322 Diffused feathery degeneration Male 19 months H 14.9 None A05 H1351 Patchy diffused hepatic cell damage (ischemia) Female 20 months H 23.5 None A06 H1334 Patchy cholestasis, feathery degeneration Female 21 months AA 22.8 None B01 H1397 Feathery and ballooning degeneration Female 21 months H 18.9 None B02 H0551 Near normal Male 2 years C 15.5 None B03 H0852 Diffused hepatic cell death (ischemia) Male 2 years H 16.1 None B04 H0872 Massive liquefaction necrosis Male 2 years C 19.3 None
    [Show full text]
  • Manual Laboratory Activity Pathology Anatomy For
    MANUAL LABORATORY ACTIVITY PATHOLOGY ANATOMY FOR STUDENT Resource Person : Ismet M. Nur., dr., SpPA(K)., MM. Module Author : Meta Maulida D., drg., M.Kes. Subject : Cell Injury, Inflammation, Neoplasm Department : Anatomic Pathology Date : January, 2020 A Sequent : I Introduction : 30 min II Pre-test : 5 min III Laboratory activity : 80 min IV Post-test : 5 min B Learning Objectives : After performing laboratory activity, the students should be able to : Describe the macroscopic and microscopic feature of: ballooning degeneration, acute hepatitis, chronic active hepatitis, chronic persistent hepatitis, cirrhosis hepatic, and hepatocellular carcinoma. C Topic : 1. Cell injury. 2. Inflammation 3. Neoplasm. D Venue : Biomedical Laboratory, Faculty of Medicine, UNISBA, Taman Sari 22, Bandung 40116 E Equipment : Poster, atlas, light microscope and preparates of : Ballooning degeneration Chronic active hepatitis Chronic persistent hepatitis Cirrhosis hepatic Hepatocellular carcinoma F Pre-requisite/ Pre-test and Task : Note: If the pre-test score less than 50, the student won't be allowed to follow laboratory activity G Implementation 1. Students are divided into 20 groups 2. Each group is supervised by one tutor Manual Laboratory Department of Anatomic Pathology Page 1 Structure of Liver Microscopic architecture of the liver parenchyma. Both a lobule and an acinus are represented. The idealized classic lobule is represented as hexagonal centered on a central vein (CV), also known as terminal hepatic venule, and has portal tracts at three of its apices. The portal tracts contain branches of the portal vein (PV), hepatic artery (HA), and the bile duct (BD) system. Regions of the lobule generally are referred to as periportal, midzonal, and centrilobular, according to their proximity to portal spaces and central vein.
    [Show full text]
  • Perinatal Exposure to Bisphenol a Exacerbates Nonalcoholic Steatohepatitis-Like Phenotype in Male Rat Offspring Fed on a High-Fat Diet
    JWEI, X SUN and others Maternal BPA exposure and 222:3 313–325 Research hepatic steatosis Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet Jie Wei2,*, Xia Sun1,*, Yajie Chen1, Yuanyuan Li, Liqiong Song, Zhao Zhou, Bing Xu, Yi Lin1 and Shunqing Xu Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Correspondence Huazhong University of Science and Technology, Wuhan 430030, China should be addressed 1Key Laboratory of Urban Environment and Health, Department of Environmental and Molecular Toxicology, to S Xu or Y Lin Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China Emails 2Department of Basic Medical Sciences, Medical College, Xiamen University, Xiamen 361102, China [email protected] or *(J Wei and X Sun contributed equally to this work) [email protected] Abstract Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is Key Words present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA " bisphenol A Journal of Endocrinology contributes to metabolic syndrome. In this study, we examined whether perinatal exposure " steatosis to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic " insulin resistance syndrome. Wistar rats were exposed to 50 mg/kg per day BPA or corn oil throughout " oxidative stress gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a " inflammation high-fat diet (HFD) after weaning.
    [Show full text]
  • Pathology of Alcoholic Liver Disease
    Review Article Pathology of Alcoholic Liver Disease Romulo Celli1 and Xuchen Zhang2 1Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; 2Pathology and Laboratory Service, VA Connecticut Health System and Department of Pathology, Yale University School of Medicine, West Haven, CT, USA Abstract (i.e. steatosis). The role of the pathologist is to assimilate the diverse morphologic data from a given liver biopsy and to Alcohol-attributable burden on global health is increasing, clearly determine progression of the disease and, if possible, and the relationship between population alcohol consumption its etiology. and liver-related deaths is strong. Longstanding scientific and Specifically, the role of liver biopsy in ALD is 1) to clinical work has led to a relatively thorough, if not complete, corroborate clinical findings in establishing diagnosis and 2) understanding of the effects of alcohol consumption on the to estimate disease severity using semi-quantitative tools of liver. Pathologic features of alcoholic liver disease (ALD) are disease grade and stage. recognized by pathologists and used to assist clinicians in The objective of this review is to survey the gross and diagnosing and determining severity of disease in patients microscopic features of ALD and, in doing so, to provide suspected of ALD. In this review, we discuss the pathologic clinicians with a reference for the interpretation of liver biopsy manifestations of ALD and provide salient points on their pathology reports. Additionally, we review the benefits and pathophysiology. In addition, the benefits and indications of limitations of obtaining a liver biopsy and provide a pre- liver biopsy and important differential diagnoses, including liminary set of indications for this clinical test.
    [Show full text]