DOCSLIB.ORG

Autoimmune Liver Disease: Overlap and Outliers

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Autoimmune Liver Disease: Overlap and Outliers Modern Pathology (2007) 20, S15–S30 & 2007 USCAP, Inc All rights reserved 0893-3952/07 $30.00 www.modernpathology.org Autoimmune liver disease: overlap and outliers Mary K Washington Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, USA The three main categories of autoimmune liver disease are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC); all are well-defined entities with diagnosis based upon a constellation of clinical, serologic, and liver pathology findings. Although these diseases are considered autoimmune in nature, the etiology and possible environmental triggers of each remain obscure. The characteristic morphologic patterns of injury are a chronic hepatitis pattern of injury with prominent plasma cells in AIH, destruction of small intrahepatic bile ducts and canals of Hering in PBC, and periductal fibrosis and inflammation involving larger bile ducts with variable small duct damage in PSC. Serological findings include the presence of antimitochondrial antibodies in PBC, antinuclear, anti-smooth muscle, and anti-LKM antibodies in AIH, and pANCA in PSC. Although most cases of autoimmune liver disease fit readily into one of these three categories, overlap syndromes (primarily of AIH with PBC or PSC) may comprise up to 10% of cases, and variant syndromes such as antimitochondrial antibody-negative PBC also occur. Sequential syndromes with transition from one form of autoimmune liver disease to another are rare. Modern Pathology (2007) 20, S15–S30. doi:10.1038/modpathol.3800684 Keywords: autoimmune liver disease; autoimmune hepatitis; primary biliary cirrhosis; primary sclerosing cholangitis; overlap syndrome The three major categories of autoimmune liver Epidemiology and Demographic Features disease are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing The worldwide prevalence of AIH is unknown; most cholangitis (PSC). Although each of these entities reported cases are in patients of European Caucasian has well-defined clinical, morphologic, and serolo- or Japanese extraction. In North American popula- tions, the prevalence is estimated as B1 per 100 000 gic profiles (Table 1), variant and atypical forms are 1 not uncommon, and overlap syndromes, primarily population. In Western Europe and North America, between AIH and PBC, and AIH and PSC are where viral hepatitis prevalence rates are relatively increasingly recognized. low, AIH accounts for roughly 20% of chronic hepatitis in the white populations. In patients of European descent, AIH is associated with the HLA A1-B8-DR3 haplotype and particu- Autoimmune hepatitis larly with DR3. In Japan, it appears to be primarily associated with the DR4 haplotype;2 this form of the Definition disease occurs in elderly patients who exhibit mild Recognized as a clinical entity for over 50 years, necroinflammatory activity and a good response to AIH is generally characterized as an unresolving immunosuppressive therapy. hepatitis usually associated with hypergamma- globulinemia and tissue-directed autoantibodies and responding in most cases to immunosuppres- Clinical Features sive therapy. The pathogenesis appears to be aberrant autoreactivity in genetically susceptible AIH, like most autoimmune disorders, is more individuals. common in female patients, with a male:female ratio of roughly 1:4. It can present at any age, but younger patients appear to have a more severe form Correspondence: Dr MK Washington, MD, PhD, Department of of the disease. Presentation varies widely, ranging Pathology, Vanderbilt University Medical Center, C-3321 Medical Center North, Nashville, TN 37232, USA. from asymptomatic elevations of serum liver en- E-mail: [email protected] zymes, to massive hepatic necrosis resulting in Received 14 July 2006; accepted 26 July 2006 fulminant hepatic failure. Most patients present Autoimmune liver disease MK Washington S16 Table 1 Autoimmune liver diseases: clinicopathologic features (adapted from Beuers73) AIH PBC PSC AICa Female:male 4:1 9:1 1:2 9:1 Predominant liver test AST, ALT Alk phos, g-GT Alk phos, g-GT Alk phos, g-GT elevation Serum Ig elevation IgG IgM IgG, IgM IgM Autoantibodies ANA, ASMA, LKM1, SLA/P, AMA, AMA-M2, gp210 p-ANCA ANA, ASMA pANCA HLA association A3, B8, DR3, DR4 DR8 (weak association) DR52 B8, DR3, DR4 Histology Interface and lobular Florid bile duct lesion Fibrosis and obliteration Florid bile duct lesion hepatitis; prominent plasma of large bile ducts; cells ductopenia Diagnosis AIH score415 for diagnosis AMA, cholestatic serum Biliary strictures and Cholestatic serum enzyme of definite AIH enzyme pattern, dilatation on pattern, AMA neg, ANA compatible histology cholangiography; or ASMA positive; cholestatic serum enzyme histology c/w PBC pattern, IBD, p-ANCA First-line medical Immunosuppression Ursodeoxycholic acid UDCA UDCA therapy (corticosteroids+ (UDCA) azathioprine) aAutoimmune cholangitis. with a prodrome phase characterized by a flulike Serum studies illness and lethargy; indeed, the latter may be Characteristic biochemical abnormalities include the only symptom. About half of the patients with elevated transaminase levels, often accompanied a prodromal phase will be icteric at some point. by hyperbilirubinemia, hypergammaglobulinemia About one-third of patients are cirrhotic at presenta- with a disproportionate increase in serum IgG, and tion, confirming the impression that AIH often normal or only slightly elevated alkaline phospha- has a prolonged subclinical phase. Approximately tase. Aminotransferases and bilirubin levels may 30% of patients, usually younger patients, will vary widely, however, and may even normalize have an acute presentation mimicking acute viral spontaneously for a period of time, and thus no hepatitis. The response to therapy and prevalence threshold level for aminotransferases for diagnosis of cirrhosis at presentation are the same as in of AIH is specified. Bilirubin and transaminase patients who present with more insidious levels do not reliably reflect disease severity. Total onset. Roughly 20% of patients will be asympto- globulins may be in the normal range, and IgM matic, with elevated transaminases identified on levels are not as elevated as in PBC. screening examination or during evaluation for Seventy to eighty percent of patients with AIH amenorrhea, thyroid disease, arthralgia, or diabetes have antinuclear antibody (ANA) or smooth muscle mellitus. Frequency of cirrhosis in this group antibody (SMA) or both (Z1:40). Because the ANA at presentation is similar to that for symptomatic react mainly with histones and DNA, the pattern is patients. In children, acute presentation is common, homogeneous, similar to that seen in lupus; other and the patients are more likely to be cirrhotic patterns also occur, with no apparent clinical (60–80%).3 significance.6 The autoantibody titer does not reli- About 50% of patients with AIH will have ably reflect disease severity. The SMA reacts with concurrent autoimmune disorders, most commonly several cytoskeletal components, including F-actin. thyroid disease or rheumatoid arthritis. The pre- Three to four percent of overall patients (usually sence of ulcerative colitis, however, should raise children) present with anti-liver kidney microsomal questions about the diagnosis of AIH; such patients (LKM1) antibodies, without ANA or SMA. This are more likely to have PSC. serologic marker is more common in southern Europe but the true prevalence is not known. The Diagnosis antibody is directed against P450(CYP)2D6 and is associated with DRB1*0701 allele.3 AIH is diagnosed by consideration of the combina- Antibodies against the soluble liver antigen/liver tion of clinical and laboratory features with pancreas antigen (SLA/LP) are found in 10–30% exclusion of other causes of liver disease such as with AIH; although testing for this autoantibody is viral hepatitis, Wilson’s disease, alpha-1-antitrypsin not routine, it appears to have a global distribution. deficiency, PBC, PSC, alcohol abuse, and drug pANCA, while not specific, is present in 60–90%.3 reaction. Diagnosis is straightforward in 50% and is aided by serum studies and the scoring system Histopathology developed by the International Autoimmune Hepa- Key histologic features of AIH are a chronic hepatitis titis Working Group.4,5 pattern of injury, with portal and periportal lym- Modern Pathology (2007) 20, S15–S30 Autoimmune liver disease MK Washington S17 phoplasmacytic infiltrates (Figure 1) and interface to immunosuppressive therapy, although relapses hepatitis (Figure 2). Plasma cells (Figure 3) are often with withdrawal of therapy are common and the but not always prominent, and are sometimes seen disease can recur following liver transplantation. singly and in clusters in the lobule. The severity of Portal plasma cell infiltrates, while on immunosup- necroinflammatory activity is quite variable, ranging pressant therapy, are associated with relapse upon from mildly active hepatitis (Figure 4) to bridging drug cessation.8,9 necrosis to massive hepatic necrosis. Hepatocyte Centrilobular injury with prominent hepatocellu- regeneration may be prominent, with regenerating lar necrosis and mononuclear inflammation occurs rosette-like structures. Ballooning degeneration, in some cases of AIH (Figure 5), either as an isolated spotty hepatocyte necrosis, and apoptotic bodies finding (rare) or in conjunction with periportal are common but not specific. Syncytial multinu- activity and
Load more

Recommended publications
  • Viral Hepatitis Testing Effective Date: January 1, 2012
    Viral Hepatitis Testing Effective Date: January 1, 2012 Scope This guideline provides guidance for the use of laboratory tests to diagnose acute and chronic viral hepatitis in adults (> 19 years) in the primary care setting. General Considerations for Ordering Laboratory Tests Prior to ordering tests for hepatitis, consider the patient’s history, age, risk factors (see below), hepatitis vaccination status, and any available previous hepatitis test results. Risk Factors for Viral Hepatitis include: • Substance use (includes sharing drug snorting, smoking or injection equipment) • High-risk sexual activity or sexual partner with viral hepatitis • Travel to or from high-risk hepatitis endemic areas or exposure during a local outbreak • Immigration from hepatitis B and/or C endemic countries • Household contact with an infected person especially if personal items (e.g., razors, toothbrushes, nail clippers) are shared • Recipient of unscreened blood products* • Needle-stick injury or other occupational exposure (e.g., healthcare workers) • Children born to mothers with chronic hepatitis B or C infection • Attendance at daycare • Contaminated food or water (hepatitis A only) • Tattoos and body piercing • History of incarceration • HIV or other sexually transmitted infection • Hemodialysis *screening of donated blood products for hepatitis C (anti-HCV) began in 1990 in Canada.1 Types of Viral Hepatitis Hepatitis A: causes acute but not chronic hepatitis Hepatitis B: causes acute and chronic hepatitis Hepatitis C: causes chronic hepatitis but rarely manifests as acute hepatitis Hepatitis D: rare and only occurs in patients infected with hepatitis B Hepatitis E: clinically similar to hepatitis A, mostly restricted to endemic areas and occasionally causes chronic infection in immunosuppressed people Others: e.g.
    [Show full text]
  • Autoimmune Hepatitis
    Page 1 of 5 Autoimmune Hepatitis Autoimmune hepatitis is an uncommon cause of chronic hepatitis (persistent liver inflammation). The cause is not known. If left untreated, the inflammation causes cirrhosis (scarring of the liver). However, with treatment, the outlook for people with this condition is very good. Treatment is usually with steroids and other medicines which suppress inflammation. What does the liver do? The liver is in the upper right part of the abdomen. It has many functions which include: Storing glycogen (fuel for the body) which is made from sugars. When required, glycogen is broken down into glucose which is released into the bloodstream. Helping to process fats and proteins from digested food. Making proteins that are essential for blood to clot (clotting factors). Processing many medicines which you may take. Helping to remove or process alcohol, poisons and toxins from the body. Making bile which passes from the liver to the gut down the bile duct. Bile breaks down the fats in food so that they can be absorbed from the bowel. What is autoimmune hepatitis? Hepatitis means inflammation of the liver. There are many causes of hepatitis. For example, alcohol excess and infections with various viruses are the common causes of hepatitis. Autoimmune hepatitis is an uncommon cause of chronic hepatitis. Chronic means that the inflammation is persistent or long-term. The chronic inflammation gradually damages the liver cells, which can result in serious problems. What causes autoimmune hepatitis? Page 2 of 5 The cause is not clear. It is thought to be an autoimmune disease. Our immune system normally defends us against infection from bacteria, viruses and other germs.
    [Show full text]
  • Prevention & Control of Viral Hepatitis Infection
    Prevention & Control of Viral Hepatitis Infection: A Strategy for Global Action © World Health Organization 2011. All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. Table of contents Disease burden 02 What is viral hepatitis? 05 Prevention & control: a tailored approach 06 Global Achievements 08 Remaining challenges 10 World Health Assembly: a mandate for comprehensive prevention & control 13 WHO goals and strategy
    [Show full text]
  • EASL Clinical Practice Guidelines: Autoimmune Hepatitisq
    Clinical Practice Guidelines EASL Clinical Practice Guidelines: Autoimmune hepatitisq ⇑ European Association for the Study of the Liver striking progress, and now patients in specialised centres have an Introduction excellent prognosis, both in respect to survival and to quality of life. Autoimmune hepatitis (AIH) was the first liver disease for which The aim of the present Clinical Practice Guideline (CPG) is to an effective therapeutic intervention, corticosteroid treatment, provide guidance to hepatologists and general physicians in the was convincingly demonstrated in controlled clinical trials. diagnosis and treatment of AIH in order to improve care for However, 50 years later AIH still remains a major diagnostic affected patients. In view of the limited data from large con- and therapeutic challenge. There are two major reasons for this trolled studies and trials, many recommendations are based on apparent contradiction: Firstly, AIH is a relatively rare disease. expert consensus. This is to some extent a limitation of this Secondly, AIH is a very heterogeneous disease. EASL-CPG, but at the same time it is its special strength: consen- Like other rare diseases, clinical studies are hampered by the sus in this guideline is based on intensive discussions of experts limited number of patients that can be included in trials. Possibly from large treatment centres. The core consensus group has and more importantly, the interest of the pharmaceutical indus- experience of over one thousand AIH patients managed person- try to develop effective specific therapies for rare diseases is lim- ally, and the recommendations have been reviewed by both the ited due to the very restricted market for such products.
    [Show full text]
  • AASLD PRACTICE GUIDELINES Diagnosis and Management of Autoimmune Hepatitis
    AASLD PRACTICE GUIDELINES Diagnosis and Management of Autoimmune Hepatitis Michael P. Manns,1 Albert J. Czaja,2 James D. Gorham,3 Edward L. Krawitt,4 Giorgina Mieli-Vergani,5 Diego Vergani,6 and John M. Vierling7 This guideline has been approved by the American ment on Guidelines;3 and (4) the experience of the Association for the Study of Liver Diseases (AASLD) authors in the specified topic. and represents the position of the Association. These recommendations, intended for use by physi- cians, suggest preferred approaches to the diagnostic, 1. Preamble therapeutic and preventive aspects of care. They are intended to be flexible, in contrast to standards of Clinical practice guidelines are defined as ‘‘systemati- care, which are inflexible policies to be followed in ev- cally developed statements to assist practitioner and ery case. Specific recommendations are based on rele- patient decisions about appropriate heath care for spe- vant published information. To more fully characterize 1 cific clinical circumstances.’’ These guidelines on the quality of evidence supporting the recommenda- autoimmune hepatitis provide a data-supported tions, the Practice Guidelines Committee of the approach to the diagnosis and management of this dis- AASLD requires a class (reflecting benefit versus risk) ease. They are based on the following: (1) formal and level (assessing strength or certainty) of evidence review and analysis of the recently-published world lit- to be assigned and reported with each recommenda- erature on the topic [Medline search]; (2) American tion.4 The grading system applied to the recommenda- College of Physicians Manual for Assessing Health tions has been adapted from the American College of 2 Practices and Designing Practice Guidelines; (3) Cardiology and the American Heart Association Prac- guideline policies, including the AASLD Policy on the tice Guidelines, and it is given below (Table 1).
    [Show full text]
  • Chronic Viral Hepatitis in a Cohort of Inflammatory Bowel Disease
    pathogens Article Chronic Viral Hepatitis in a Cohort of Inflammatory Bowel Disease Patients from Southern Italy: A Case-Control Study Giuseppe Losurdo 1,2 , Andrea Iannone 1, Antonella Contaldo 1, Michele Barone 1 , Enzo Ierardi 1 , Alfredo Di Leo 1,* and Mariabeatrice Principi 1 1 Section of Gastroenterology, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy; [email protected] (G.L.); [email protected] (A.I.); [email protected] (A.C.); [email protected] (M.B.); [email protected] (E.I.); [email protected] (M.P.) 2 Ph.D. Course in Organs and Tissues Transplantation and Cellular Therapies, Department of Emergency and Organ Transplantation, University “Aldo Moro” of Bari, 70124 Bari, Italy * Correspondence: [email protected]; Tel.: +39-080-559-2925 Received: 14 September 2020; Accepted: 21 October 2020; Published: 23 October 2020 Abstract: We performed an epidemiologic study to assess the prevalence of chronic viral hepatitis in inflammatory bowel disease (IBD) and to detect their possible relationships. Methods: It was a single centre cohort cross-sectional study, during October 2016 and October 2017. Consecutive IBD adult patients and a control group of non-IBD subjects were recruited. All patients underwent laboratory investigations to detect chronic hepatitis B (HBV) and C (HCV) infection. Parameters of liver function, elastography and IBD features were collected. Univariate analysis was performed by Student’s t or chi-square test. Multivariate analysis was performed by binomial logistic regression and odds ratios (ORs) were calculated. We enrolled 807 IBD patients and 189 controls. Thirty-five (4.3%) had chronic viral hepatitis: 28 HCV (3.4%, versus 5.3% in controls, p = 0.24) and 7 HBV (0.9% versus 0.5% in controls, p = 0.64).
    [Show full text]
  • Primary Biliary Cholangitis: a Brief Overview Justin S
    REVIEW Primary Biliary Cholangitis: A Brief Overview Justin S. Louie,* Sirisha Grandhe,* Karen Matsukuma,† and Christopher L. Bowlus* Primary biliary cholangitis (PBC), previously referred to supported by the higher concordance of PBC in monozy- as primary biliary cirrhosis, is the most common chronic gotic compared with dizygotic twins.4 In addition, certain cholestatic autoimmune disease affecting adults in the human leukocyte antigen haplotypes have been associ- United States.1 It is characterized by a hallmark serologic ated with PBC, as well as variants at loci along the inter- signature, antimitochondrial antibody (AMA), and specific leukin-12 (IL-12) immunoregulatory pathway (IL-12A and bile duct pathology with progressive intrahepatic duct de- IL-12RB2 loci).5 struction leading to cholestasis. PBC is potentially fatal and can have both intrahepatic and extrahepatic complications. PATHOGENESIS EPIDEMIOLOGY The primary disease mechanism in PBC is thought to be T cell lymphocyte–mediated injury against intralobu- PBC affects all races and ethnicities; however, it is best lar biliary epithelial cells. This causes progressive destruc- studied in the Caucasian population. The condition pre- tion and eventual disappearance of the intralobular bile dominantly affects women older than 40 years, with a ducts. Molecular mimicry has been proposed as the ini- female/male ratio of 9:1.2 Although the incidence of PBC tiating event in the loss of tolerance primarily to mito- appears to be stable, the overall prevalence of the disease chondrial pyruvate dehydrogenase complex, E2, during is increasing.3 An individual’s genetic susceptibility, epige- which exogenous antigens evoke an immune response netic factors, and certain environmental triggers seem to that recognizes an endogenous (self) antigen inciting an play important roles.
    [Show full text]
  • Hepatitis A, B, and C: Learn the Differences
    Hepatitis A, B, and C: Learn the Differences Hepatitis A Hepatitis B Hepatitis C caused by the hepatitis A virus (HAV) caused by the hepatitis B virus (HBV) caused by the hepatitis C virus (HCV) HAV is found in the feces (poop) of people with hepa- HBV is found in blood and certain body fluids. The virus is spread HCV is found in blood and certain body fluids. The titis A and is usually spread by close personal contact when blood or body fluid from an infected person enters the body virus is spread when blood or body fluid from an HCV- (including sex or living in the same household). It of a person who is not immune. HBV is spread through having infected person enters another person’s body. HCV can also be spread by eating food or drinking water unprotected sex with an infected person, sharing needles or is spread through sharing needles or “works” when contaminated with HAV. “works” when shooting drugs, exposure to needlesticks or sharps shooting drugs, through exposure to needlesticks on the job, or from an infected mother to her baby during birth. or sharps on the job, or sometimes from an infected How is it spread? Exposure to infected blood in ANY situation can be a risk for mother to her baby during birth. It is possible to trans- transmission. mit HCV during sex, but it is not common. • People who wish to be protected from HAV infection • All infants, children, and teens ages 0 through 18 years There is no vaccine to prevent HCV.
    [Show full text]
  • Active Peptic Ulcer Disease in Patients with Hepatitis C Virus-Related Cirrhosis: the Role of Helicobacter Pylori Infection and Portal Hypertensive Gastropathy
    dore.qxd 7/19/2004 11:24 AM Page 521 View metadata, citation and similar papers at core.ac.uk ORIGINAL ARTICLE brought to you by CORE provided by Crossref Active peptic ulcer disease in patients with hepatitis C virus-related cirrhosis: The role of Helicobacter pylori infection and portal hypertensive gastropathy Maria Pina Dore MD PhD, Daniela Mura MD, Stefania Deledda MD, Emmanouil Maragkoudakis MD, Antonella Pironti MD, Giuseppe Realdi MD MP Dore, D Mura, S Deledda, E Maragkoudakis, Ulcère gastroduodénal évolutif chez les A Pironti, G Realdi. Active peptic ulcer disease in patients patients atteints de cirrhose liée au HCV : Le with hepatitis C virus-related cirrhosis: The role of Helicobacter pylori infection and portal hypertensive rôle de l’infection à Helicobacter pylori et de la gastropathy. Can J Gastroenterol 2004;18(8):521-524. gastropathie liée à l’hypertension portale BACKGROUND & AIM: The relationship between Helicobacter HISTORIQUE ET BUT : Le lien entre l’infection à Helicobacter pylori pylori infection and peptic ulcer disease in cirrhosis remains contro- et l’ulcère gastroduodénal dans la cirrhose reste controversé. Le but de la versial. The purpose of the present study was to investigate the role of présente étude est de vérifier le rôle de l’infection à H. pylori et de la gas- H pylori infection and portal hypertension gastropathy in the preva- tropathie liée à l’hypertension portale dans la prévalence de l’ulcère gas- lence of active peptic ulcer among dyspeptic patients with compen- troduodénal évolutif chez les patients dyspeptiques souffrant d’une sated hepatitis C virus (HCV)-related cirrhosis.
    [Show full text]
  • Understanding Human Astrovirus from Pathogenesis to Treatment
    University of Tennessee Health Science Center UTHSC Digital Commons Theses and Dissertations (ETD) College of Graduate Health Sciences 6-2020 Understanding Human Astrovirus from Pathogenesis to Treatment Virginia Hargest University of Tennessee Health Science Center Follow this and additional works at: https://dc.uthsc.edu/dissertations Part of the Diseases Commons, Medical Sciences Commons, and the Viruses Commons Recommended Citation Hargest, Virginia (0000-0003-3883-1232), "Understanding Human Astrovirus from Pathogenesis to Treatment" (2020). Theses and Dissertations (ETD). Paper 523. http://dx.doi.org/10.21007/ etd.cghs.2020.0507. This Dissertation is brought to you for free and open access by the College of Graduate Health Sciences at UTHSC Digital Commons. It has been accepted for inclusion in Theses and Dissertations (ETD) by an authorized administrator of UTHSC Digital Commons. For more information, please contact [email protected]. Understanding Human Astrovirus from Pathogenesis to Treatment Abstract While human astroviruses (HAstV) were discovered nearly 45 years ago, these small positive-sense RNA viruses remain critically understudied. These studies provide fundamental new research on astrovirus pathogenesis and disruption of the gut epithelium by induction of epithelial-mesenchymal transition (EMT) following astrovirus infection. Here we characterize HAstV-induced EMT as an upregulation of SNAI1 and VIM with a down regulation of CDH1 and OCLN, loss of cell-cell junctions most notably at 18 hours post-infection (hpi), and loss of cellular polarity by 24 hpi. While active transforming growth factor- (TGF-) increases during HAstV infection, inhibition of TGF- signaling does not hinder EMT induction. However, HAstV-induced EMT does require active viral replication.
    [Show full text]
  • Hepatitis C 2005 Clinical Guidelines Summary of The: New York State Department of Health Clinical Guidelines for the Medical Management of Hepatitis C
    Hepatitis C 2005 Clinical Guidelines Summary of the: New York State Department of Health Clinical Guidelines for the Medical Management of Hepatitis C Inside: Key Features of Viral Hepatitis A,B and C 1 Natural Course of HCV Infection 2 Persons at Risk for HCV Infection 3 Sources of HCV Infection 4 Counseling Prior To Testing 5 Screening for HCV Algorithm 6 Laboratory Testing for HCV 7 Interpretation of HCV Test Results 8 Post Exposure Screening for HCV 9 Counseling After Testing 10 Treating HCV Patients 11 Medical Management of HCV Positive Patients 12 References and Internet Resources 13 Hepatitis C Virus The Hidden Epidemic The Burden of HCV • 3 million Americans are chronically infected with the • 8-10,000 deaths a year are caused by HCV. Hepatitis C virus (HCV). • HCV is the leading cause for liver transplants and • 342,000 New Yorkers are estimated to be infected chronic liver disease. with HCV. • HCV deaths will increase four-fold to 38,000, by • A majority of the people infected with HCV do not the year 2010. know they have it. • Years of life lost to Hepatitis C (2001-2019) • Thousands of people go undetected each year—due 3.1 million years to inadequate risk assessment, under-screening and confusion about the use of diagnostic tests. • Cost of premature disability and death (2010-2109) $75.5 billion Hepatitis C Virus • Direct medical costs in absentee losses due to Hepatitis C $750 million/ year • HCV is a blood-borne disease transmitted by • Total medical expenditures for persons with HCV blood-to-blood contact.
    [Show full text]
  • Hepatitis C Virus Infection and Human Pancreatic ß-Cell Dysfunction
    Pathophysiology/Complications BRIEF REPORT Hepatitis C Virus Infection and Human Pancreatic ␤-Cell Dysfunction 1 1 MATILDE MASINI, MD SILVIA DEL GUERRA, PHD showing the characteristic insulin gran- 2 1 DANIELA CAMPANI, MD MARCO BUGLIANI, PHD ules and normally preserved mitochon- 3 1 UGO BOGGI, MD SCILLA TORRI, PHD ␤ 2 1 dria. In -cells from HCV-positive MICHELE MENICAGLI, MD STEFANO DEL PRATO, MD 1 3 pancreases, the presence of virus-like par- NICOLA FUNEL, MD FRANCO MOSCA, MD 1 4 ticles was observed, mainly close to the MARIA POLLERA, MD FRANCO FILIPPONI, MD 1 1 membranes of Golgi apparatus, which, in ROBERTO LUPI, PHD PIERO MARCHETTI, MD, PHD turn, appeared hyperplastic and dilated (Fig. 1D). The mitochondria appeared round-shaped with dispersed matrix and fragmented cristae (Fig. 1D). Additional Ϯ 2 any patients with chronic hepati- and 2 women, BMI 25.8 1.6 kg/m ) ␤-cell changes were observed at the Ϯ tis C virus (HCV) develop type 2 and 10 HCV-negative (age 67 9 years, level of rough endoplasmic reticulum, Ϯ diabetes (1). This prevalence is 6 men and 4 women, BMI 26.8 2.0 which showed long and dilated tubular M 2 much higher than that observed in the kg/m ) donors were harvested and stud- membranes, with numerous electron- general population and in patients with ied with the approval of our local ethics dense ribosomes bound to the latter (not other chronic liver diseases such as hepa- committee. Histological studies were shown). These morphological changes titis B virus, alcoholic liver disease, and performed by immunohistochemistry were accompanied by reduced in vitro primary biliary cirrhosis.
    [Show full text]