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Khrom M, Long M, Dube S, Robbins L, Botwin GJ, Yang S, Mengesha E, Li D, Naito T, Bonthala NN, Ha C, Melmed G, Rabizadeh S, Syal G, Vasiliauskas E, Ziring D, Brant SR, Cho J, Duerr RH, Rioux J, Schumm P, Silverberg M, Ananthakrishnan AN, Faubion WA, Jabri B, Lira SA, Newberry RD, Sandler RS, Xavier RJ, Kugathasan S, Hercules D, Targan SR, Sartor RB, Haritunians T, McGovern DPB. Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease. Gastroenterology 2024; 167:315-332. [PMID: 38490347 PMCID: PMC11193636 DOI: 10.1053/j.gastro.2024.02.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2022] [Revised: 02/11/2024] [Accepted: 02/13/2024] [Indexed: 03/17/2024]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.
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MESH Headings
- Humans
- Female
- Male
- Adult
- Cholangitis, Sclerosing/immunology
- Cholangitis, Sclerosing/genetics
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/complications
- Middle Aged
- Colitis, Ulcerative/immunology
- Colitis, Ulcerative/genetics
- Colitis, Ulcerative/diagnosis
- Crohn Disease/immunology
- Crohn Disease/genetics
- Crohn Disease/diagnosis
- Adolescent
- Risk Factors
- Child
- Spondylitis, Ankylosing/genetics
- Spondylitis, Ankylosing/immunology
- Spondylitis, Ankylosing/diagnosis
- Spondylitis, Ankylosing/complications
- Genetic Predisposition to Disease
- Young Adult
- Sex Factors
- Skin Diseases/etiology
- Skin Diseases/immunology
- Skin Diseases/genetics
- Eye Diseases/etiology
- Eye Diseases/immunology
- Eye Diseases/diagnosis
- Eye Diseases/genetics
- Eye Diseases/epidemiology
- Phenotype
- Inflammatory Bowel Diseases/genetics
- Inflammatory Bowel Diseases/immunology
- Inflammatory Bowel Diseases/diagnosis
- Logistic Models
- Aged
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Affiliation(s)
- Michelle Khrom
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Millie Long
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Shishir Dube
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Lori Robbins
- Palmetto Digestive Health Specialists, Charleston, South Carolina
| | - Gregory J Botwin
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shaohong Yang
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Emebet Mengesha
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dalin Li
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Takeo Naito
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Nirupama N Bonthala
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Christina Ha
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gil Melmed
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Shervin Rabizadeh
- Department of Pediatrics, Pediatric Inflammatory Bowel Disease Program, Cedars-Sinai Medical Center, Los Angeles, California
| | - Gaurav Syal
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Eric Vasiliauskas
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - David Ziring
- Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California
| | - Steven R Brant
- Division of Gastroenterology and Hepatology, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey
| | - Judy Cho
- Icahn School of Medicine at Mount Sinai, Dr Henry D. Janowitz Division of Gastroenterology, New York, New York
| | - Richard H Duerr
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - John Rioux
- Department of Medicine, Université de Montréal and Research Center, Montreal Heart Institute, Montréal, Québec, Canada
| | - Phil Schumm
- Department of Public Health Sciences, University of Chicago, Chicago, Illinois
| | - Mark Silverberg
- University of Toronto, Samuel Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada
| | | | | | - Bana Jabri
- University of Chicago, Pritzker School of Medicine, Chicago, Illinois
| | - Sergio A Lira
- Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Rodney D Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri
| | - Robert S Sandler
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Ramnik J Xavier
- Broad Institute of MIT and Harvard, Cambridge, Massachusetts
| | - Subra Kugathasan
- Children's Healthcare of Atlanta Combined Center for Pediatric Inflammatory Bowel Disease, Atlanta, Georgia; Emory School of Medicine, Atlanta, Georgia
| | | | - Stephan R Targan
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - R Balfour Sartor
- Center for Gastrointestinal Biology and Disease, University of North Carolina, Chapel Hill, North Carolina
| | - Talin Haritunians
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California
| | - Dermot P B McGovern
- F. Widjaja Inflammatory Bowel Disease Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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Stratmann K, Aydolmus S, Gu W, Heling D, Spengler U, Terjung B, Strassburg CP, Vollenberg R, Blumenstein I, Trebicka J. Hepatobiliary manifestations in patients with ulcerative colitis: a retrospective analysis. Front Med (Lausanne) 2024; 10:1273797. [PMID: 38249970 PMCID: PMC10796802 DOI: 10.3389/fmed.2023.1273797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 12/18/2023] [Indexed: 01/23/2024] Open
Abstract
Background Inflammatory bowel diseases (IBDs) are often associated with altered liver function tests (LFTs). There is little data on the relationship between abnormal LFT and IBD. Our study aimed to evaluate the prevalence and etiology of elevated LFT in patients with ulcerative colitis (UC) and to determine whether there is an association with clinical and demographic parameters. Methods The clinical records of the Gastroenterology Outpatients Clinic at a single center were reviewed and screened for patients with UC from 2005 to 2014. In total, 263 patients were included. Patients with Crohn's disease (CD), colitis indeterminate, and colitis of other origins were excluded. Abnormal LFT and liver injuries were analyzed. Results A cohort of 182 patients was analyzed (114 males, 68 females; mean age = 50.2 ± 16.1 years). 58 patients had already been diagnosed with a hepatobiliary disorder. Patients with a known hepatobiliary disorder suffered from UC for a significantly longer duration. Elevated LFT in patients without known hepatobiliary disorders was 69.4%. Liver injury was found in 21.8%. A transient increase in abnormal LFT was shown in 59 patients (68.6%), a persistent increase was found in 27 patients (31.4%). Treatment with thiopurines was a risk factor for persistent elevated LFT (p = 0.029), steroids had a protective impact (p = 0.037). Conclusion This study clearly highlights the importance of screening for hepatobiliary disorders and abnormal LFT in patients with UC, as the prevalence of hepatobiliary disorders and abnormal LFT is detected very often among this patient group.
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Affiliation(s)
- Katharina Stratmann
- Goethe University Frankfurt, University Hospital, Medical Clinic 1, Frankfurt, Germany
| | - Songül Aydolmus
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Wenyi Gu
- Department of Internal Medicine B, University Clinic Münster, Münster, Germany
| | - Dominik Heling
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Ulrich Spengler
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | - Birgit Terjung
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
| | | | - Richard Vollenberg
- Department of Internal Medicine B, University Clinic Münster, Münster, Germany
| | - Irina Blumenstein
- Goethe University Frankfurt, University Hospital, Medical Clinic 1, Frankfurt, Germany
| | - Jonel Trebicka
- Goethe University Frankfurt, University Hospital, Medical Clinic 1, Frankfurt, Germany
- Department of Internal Medicine I, University Hospital of Bonn, Bonn, Germany
- Department of Internal Medicine B, University Clinic Münster, Münster, Germany
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van Munster KN, Bergquist A, Ponsioen CY. Inflammatory bowel disease and primary sclerosing cholangitis: One disease or two? J Hepatol 2024; 80:155-168. [PMID: 37940453 DOI: 10.1016/j.jhep.2023.09.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 09/01/2023] [Accepted: 09/29/2023] [Indexed: 11/10/2023]
Abstract
Primary sclerosing cholangitis (PSC) was declared one of the biggest unmet needs in hepatology during International Liver Congress 2016 in Berlin. Since then, not much has changed unfortunately, largely due to the still elusive pathophysiology of the disease. One of the most striking features of PSC is its association with inflammatory bowel disease (IBD), with the majority of patients with PSC being diagnosed with extensive colitis. This review describes the epidemiology of IBD in PSC, its specific phenotype, complications and potential pathophysiological mechanisms connecting the two diseases. Whether PSC is merely an extra-intestinal manifestation of IBD or if PSC and IBD are two distinct diseases that happen to share a common susceptibility that leads to a dual phenotype is debated. Implications for the management of the two diseases together are also discussed. Overall, this review summarises the available data in PSC-IBD and discusses whether PSC and IBD are one or two disease(s).
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Affiliation(s)
- Kim N van Munster
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, the Netherlands
| | - Annika Bergquist
- Department of Medicine Huddinge, Division of Hepatology, Karolinska Institutet, Department of Upper GI Disease, Karolinska University Hospital, Stockholm, Sweden
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, the Netherlands.
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Miyazu T, Ishida N, Asai Y, Tamura S, Tani S, Yamade M, Iwaizumi M, Hamaya Y, Osawa S, Baba S, Sugimoto K. Intrahepatic cholangiocarcinoma in patients with primary sclerosing cholangitis and ulcerative colitis: Two case reports. World J Gastrointest Surg 2023; 15:1224-1231. [PMID: 37405109 PMCID: PMC10315124 DOI: 10.4240/wjgs.v15.i6.1224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 03/10/2023] [Accepted: 04/12/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is an extraintestinal manifestation of ulcerative colitis (UC). PSC is a well-known risk factor for intrahepatic cholangiocarcinoma (ICC), and ICC is known to have a poor prognosis.
CASE SUMMARY We present two cases of ICC in patients with PSC associated with UC. In the first case, a tumor was found by magnetic resonance imaging (MRI) in the liver of a patient with PSC and UC who presented to our hospital with right-sided rib pain. The second patient was asymptomatic, but we unexpectedly detected two liver tumors in an MRI performed to evaluate bile duct stenosis associated with PSC. ICC was strongly suspected by computed tomography and MRI in both cases, and surgery was performed, but unfortunately, the first patient died of ICC recurrence 16 mo postoperatively, and the second patient died of liver failure 14 mo postoperatively.
CONCLUSION Careful follow-up of patients with UC and PSC with imaging and blood tests is necessary for early detection of ICC.
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Affiliation(s)
- Takahiro Miyazu
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Natsuki Ishida
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yusuke Asai
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Tamura
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Shinya Tani
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Mihoko Yamade
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Moriya Iwaizumi
- Department of Laboratory Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Yasushi Hamaya
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Osawa
- Department of Endoscopic and Photodynamic Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Satoshi Baba
- Department of Diagnostic Pathology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
| | - Ken Sugimoto
- First Department of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
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5
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Hov JR, Karlsen TH. The microbiota and the gut-liver axis in primary sclerosing cholangitis. Nat Rev Gastroenterol Hepatol 2023; 20:135-154. [PMID: 36352157 DOI: 10.1038/s41575-022-00690-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/13/2022] [Indexed: 11/11/2022]
Abstract
Primary sclerosing cholangitis (PSC) offers unique opportunities to explore the gut-liver axis owing to the close association between liver disease and colonic inflammation. It is well established that the gut microbiota in people with PSC differs from that of healthy individuals, but details of the microbial factors that demarcate PSC from inflammatory bowel disease (IBD) without PSC are poorly understood. In this Review, we aim to provide an overview of the latest literature on the gut microbiome in PSC and PSC with IBD, critically examining hypotheses on how microorganisms could contribute to the pathogenesis of PSC. A particular emphasis will be put on pathogenic features of the gut microbiota that might explain the occurrence of bile duct inflammation and liver disease in the context of IBD, and we postulate the potential existence of a specific yet unknown factor related to the gut-liver axis as causative in PSC. Available data are scrutinized in the perspective of therapeutic approaches related to the gut-liver axis.
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Affiliation(s)
- Johannes R Hov
- Norwegian PSC Research Center and Section of gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway.,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Tom H Karlsen
- Norwegian PSC Research Center and Section of gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital, Oslo, Norway. .,Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
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6
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Wang CR, Tsai HW. Seronegative spondyloarthropathy-associated inflammatory bowel disease. World J Gastroenterol 2023; 29:450-468. [PMID: 36688014 PMCID: PMC9850936 DOI: 10.3748/wjg.v29.i3.450] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/18/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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7
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Hepatic manifestations of systemic disease: an imaging-based review. Pediatr Radiol 2022; 52:852-864. [PMID: 34797394 DOI: 10.1007/s00247-021-05222-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 08/28/2021] [Accepted: 10/05/2021] [Indexed: 10/19/2022]
Abstract
The liver is responsible for many processes that maintain human metabolic homeostasis and can be affected by several pediatric systemic diseases. In this manuscript, we explore key pathological findings and imaging features across multiple modalities of a spectrum of congenital, metabolic and autoimmune disorders. Strengthening the radiologists' knowledge regarding potential hepatic manifestations of these systemic diseases will ultimately lead to improved care for pediatric patients.
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8
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Characteristic features of ulcerative colitis with concomitant primary sclerosing cholangitis. PRZEGLAD GASTROENTEROLOGICZNY 2021; 16:184-187. [PMID: 34584578 PMCID: PMC8456759 DOI: 10.5114/pg.2021.108983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Accepted: 01/30/2021] [Indexed: 11/17/2022]
Abstract
Ulcerative colitis is a chronic inflammatory bowel disease of the colon. The most frequent symptoms include bloody diarrhoea with rectal urgency and tenesmus. It is often complicated by the presence of primary sclerosing cholangitis, a chronic, cholestatic liver disease, characterised by the inflammation and fibrosis of bile ducts. The presence of primary sclerosing cholangitis seems to alter the course of ulcerative colitis, changing its natural course.
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Ansari AS, Bertalot C, Mathews D, Mathews JP. Bilateral occlusive retinal vasculitis associated with primary sclerosing cholangitis. Saudi J Ophthalmol 2021; 34:310-312. [PMID: 34527880 PMCID: PMC8409361 DOI: 10.4103/1319-4534.322598] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 10/27/2019] [Accepted: 12/05/2019] [Indexed: 11/21/2022] Open
Abstract
We present the case of a 46-year-old man who presented with bilateral panuveitis and occlusive retinal vasculitis 6 months after being acutely admitted with abnormal liver function and diagnosed with primary sclerosing cholangitis (PSC). Initial investigations by the medical and ophthalmic departments including all autoimmune investigations were within normal parameters. Of particular interest was the high likelihood of inadvertent androgenic-anabolic steroid self-suppression of disease. As a lifelong bodybuilder, the patient had been taking oral and intramuscular steroids for years. He became symptomatic upon cessation of these recreational medications. There remains a significant paucity of information describing the relationship between uveitis and PSC. Given the poorly understood aetiology of this rare cholestatic disease, we review the current literature and highlight the diagnostic and therapeutic challenges for such a patient. PSC may predispose patients to an occlusive panuveitis with androgenic-anabolic steroids suppressing ocular autoimmune disease.
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Affiliation(s)
- Abdus S Ansari
- Department of Ophthalmology, Stanley Eye Unit, Betsi Cadwaladr University Health Board United Kingdom, Abergele, Wales, UK
| | - Catrin Bertalot
- Department of Ophthalmology, Stanley Eye Unit, Betsi Cadwaladr University Health Board United Kingdom, Abergele, Wales, UK
| | - Divya Mathews
- Department of Ophthalmology, Stanley Eye Unit, Betsi Cadwaladr University Health Board United Kingdom, Abergele, Wales, UK
| | - John P Mathews
- Department of Ophthalmology, Stanley Eye Unit, Abergele Hospital, Abergele, Wales, UK
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10
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Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA. Can J Gastroenterol Hepatol 2021; 2021:9936932. [PMID: 34545326 PMCID: PMC8449715 DOI: 10.1155/2021/9936932] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 08/24/2021] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Patients diagnosed with ulcerative colitis (UC) associated with primary sclerosis cholangitis (PSC) and sessile serrated adenoma (SSA) are rare. The present study aimed to identify the potential causative gene mutation in a patient with UC associated with PSC and SSA. METHODS DNA was extracted from the blood sample and tissue sample of SSA, followed by the whole exome sequencing (WES) analysis. Bioinformatics analysis was utilized to predict the deleteriousness of the identified variants. Multiple sequence alignment and conserved protein domain analyses were performed using online software. Sanger sequencing was used to validate the identified variants. Expression and diagnostic analysis of identified mutated genes was performed in the GSE119600 dataset (peripheral blood samples of PSC and UC) and GSE43841 dataset (tumor samples of SSA). RESULTS In the present study, a total of 842 single nucleotide variants (SNVs) in 728 genes were identified in the blood sample. Two variants, integrin beta 4 (ITGB4) (c.C2503G; p.P835A) and a mucin 3A (MUC3A) (c.C1019T; p.P340L), were further analyzed. MUC3A was associated with inflammatory bowel disease. Sanger sequence in blood revealed that the ITGB4 mutation was fully cosegregated with the result of WES in the patient. Additionally, a variant, tumor protein p53 gene (TP53) (c.86delA; p.N29Tfs ∗ 15) was identified in the tissue sample of SSA. Compared to that in normal controls, ITGB4 was upregulated in both UC and PSC, MUC3A was, respectively, upregulated and downregulated in PSC and UC, and TP53 was downregulated in SSA. ITGB4 and TP53 had a potential diagnostic value for UC, PSC and SSA. CONCLUSIONS The present study demonstrated that the ITGB4 (c.C2503G; p.P835A) and MUC3A (c.C1019T; p.P340L) mutations may be the potential causative variants in a patient with UC associated with PSC and SSA. TP53 (c.86delA; p.N29Tfs ∗ 15) mutation may be associated with SSA in this patient.
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11
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Zeng XY, Li M. Looking into key bacterial proteins involved in gut dysbiosis. World J Methodol 2021; 11:130-143. [PMID: 34322365 PMCID: PMC8299906 DOI: 10.5662/wjm.v11.i4.130] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 05/11/2021] [Accepted: 06/16/2021] [Indexed: 02/06/2023] Open
Abstract
The gastrointestinal microbiota plays a pivotal role in health and has been linked to many diseases. With the rapid accumulation of pyrosequencing data of the bacterial composition, the causal-effect relationship between specific dysbiosis features and diseases is now being explored. The aim of this review is to describe the key functional bacterial proteins and antigens in the context of dysbiosis related-diseases. We subjectively classify the key functional proteins into two categories: Primary key proteins and secondary key proteins. The primary key proteins mainly act by themselves and include biofilm inhibitors, toxin degraders, oncogene degraders, adipose metabolism modulators, anti-inflammatory peptides, bacteriocins, host cell regulators, adhesion and invasion molecules, and intestinal barrier regulators. The secondary key proteins mainly act by eliciting host immune responses and include flagellin, outer membrane proteins, and other autoantibody-related antigens. Knowledge of key bacterial proteins is limited compared to the rich microbiome data. Understanding and focusing on these key proteins will pave the way for future mechanistic level cause-effect studies of gut dysbiosis and diseases.
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Affiliation(s)
- Xin-Yu Zeng
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
| | - Ming Li
- Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
- Laboratory of Translational Gastroenterology, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
- Robot Engineering Laboratory for Precise Diagnosis and Therapy of GI Tumors, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
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12
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Abstract
Chronic liver disease in pregnancy is rare. Historically, many chronic liver diseases were considered contraindications to pregnancy; however, with current monitoring and treatment strategies, pregnancy may be considered in many cases. Preconception and initial antepartum consultation should focus on disease activity, medication safety, risks of pregnancy, as well as the need for additional monitoring during pregnancy. In most cases, a multidisciplinary approach is necessary to ensure optimal maternal and fetal outcomes. Despite improving outcomes, pregnancy in women with the chronic liver disease remains high risk.
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13
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Rabiee A, Silveira MG. Primary sclerosing cholangitis. Transl Gastroenterol Hepatol 2021; 6:29. [PMID: 33824933 DOI: 10.21037/tgh-20-266] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/19/2020] [Indexed: 12/15/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease characterized by inflammatory destruction of the intrahepatic and/or extrahepatic bile ducts, leading to bile stasis, fibrosis, and ultimately to cirrhosis, and often requires liver transplantation (LT). PSC occurs more commonly in men, and is typically diagnosed between the ages of 30 and 40. Most cases occur in association with inflammatory bowel disease (IBD), which often precedes the development of PSC. PSC is usually diagnosed after detection of cholestasis during health evaluation or screening of patients with IBD. When symptomatic, the most common presenting symptoms are abdominal pain, pruritus, jaundice or fatigue. The etiology of PSC is poorly understood, but an increasing body of evidence supports the concept of cholangiocyte injury as a result of environmental exposure and an abnormal immune response in genetically susceptible individuals. PSC is a progressive disease, yet no effective medical therapy for halting disease progression has been identified. Management of PSC is mainly focused on treatment of symptoms and addressing complications. PSC can be complicated by bacterial cholangitis, dominant strictures (DSs), gallbladder polyps and adenocarcinoma, cholangiocarcinoma (CCA) and, in patients with IBD, colorectal malignancy. CCA is the most common malignancy in PSC with a cumulative lifetime risk of 10-20%, and accounts for a large proportion of mortality in PSC. LT is currently the only life-extending therapeutic approach for eligible patients with end-stage PSC, ultimately required in approximately 40% of patients. LT secondary to PSC has an excellent outcome compared to other LT indications, although the disease can recur and result in morbidity post-transplant.
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Affiliation(s)
- Anahita Rabiee
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
| | - Marina G Silveira
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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14
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Stellingwerf ME, Bemelman WA, Löwenberg M, Ponsioen CY, D'Haens GR, van Dieren S, Buskens CJ. A nationwide database study on colectomy and colorectal cancer in ulcerative colitis: what is the role of appendectomy? Colorectal Dis 2021; 23:64-73. [PMID: 32524670 DOI: 10.1111/codi.15184] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 05/20/2020] [Indexed: 02/08/2023]
Abstract
AIM Although has been suggested that an appendectomy has a positive effect on the disease course in patients with ulcerative colitis (UC), recent studies indicate a potential increase in risk of colectomy and colorectal cancer (CRC). This study aimed to evaluate the rates of colectomy and CRC after appendectomy in UC patients using a nationwide prospective database [the Initiative on Crohn and Colitis Parelsnoer Institute - Inflammatory Bowel Disease (ICC PSI-IBD) database]. METHOD All UC patients were retrieved from the ICC PSI-IBD database between January 2007 and May 2018. Primary outcomes were colectomy and CRC. Outcomes were compared in patients with and without appendectomy, with a separate analysis for timing of appendectomy (before or after UC diagnosis). RESULTS A total of 826 UC patients (54.7% female; median age 46 years, range 18-89 years) were included. Sixty-three (7.6%) patients had previously undergone appendectomy: 24 (38.1%) before and 33 (52.4%) after their diagnosis of UC. In multivariate analysis, appendectomy after UC diagnosis was associated with a significantly lower colectomy rate compared with no appendectomy [hazard ratio (HR) 0.16, 95% C: 0.04-0.66, P = 0.011], and the same nonsignificant trend was seen in patients with an appendectomy before UC diagnosis (HR 0.35, 95% CI 0.08-1.41, P = 0.138). Appendectomy was associated with delayed colectomy, particularly when it was performed after diagnosis of UC (P = 0.009). No significant differences were found in the CRC rate between patients with and without appendectomy (1.6% vs 1.2%; P = 0.555). CONCLUSION Appendectomy in established UC is associated with an 84% decreased risk of colectomy and a delay in surgery. Since the colon is in situ for longer, the risk of developing CRC remains, which underscores the importance of endoscopic surveillance programmes.
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Affiliation(s)
- M E Stellingwerf
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - W A Bemelman
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - M Löwenberg
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - C Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - G R D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - S van Dieren
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - C J Buskens
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
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15
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Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis. Clin Gastroenterol Hepatol 2020; 18:2295-2304.e2. [PMID: 32068151 DOI: 10.1016/j.cgh.2020.02.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 01/29/2020] [Accepted: 02/03/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. METHODS We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. RESULTS Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083). CONCLUSIONS In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.
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16
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Aranake-Chrisinger J, Dassopoulos T, Yan Y, Nalbantoglu ILK. Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation. World J Gastroenterol 2020; 26:4126-4139. [PMID: 32821074 PMCID: PMC7403798 DOI: 10.3748/wjg.v26.i28.4126] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/08/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) associated inflammatory bowel disease (IBD) is a unique form of IBD (PSC-IBD) with distinct clinical and histologic features from ulcerative colitis (UC) and Crohn disease (CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other.
AIM To study the histologic and clinical features of PSC patients with and without IBD.
METHODS We assessed specimens from patients with UC (n = 28), CD (n = 10), PSC and UC (PSC-UC; n = 26); PSC and CD (PSC-CD; n = 6); and PSC and no IBD (PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation (OLT) were noted.
RESULTS PSC-UC patients had more isolated right-sided disease (P = 0.03), and less active inflammation in left colon, rectum (P = 0.03 and P = 0.0006), and overall (P = 0.0005) compared to UC. They required less steroids (P = 0.01) and fewer colectomies (P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC (P = 0.1). PSC-IBD (PSC-UC and PSC-CD) patients with OLT had severe disease in the left colon and rectum (P = 0.04).
CONCLUSION PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.
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Affiliation(s)
- John Aranake-Chrisinger
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | | | - Yan Yan
- Departments of Surgery and Biostatistics, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | - ILKe Nalbantoglu
- Department of Anatomic Pathology, Yale University School of Medicine, New Haven, CT 06525, United States
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
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17
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Bhat P, Aabakken L. Role of Endoscopy in Primary Sclerosing Cholangitis. Clin Endosc 2020; 54:193-201. [PMID: 32380796 PMCID: PMC8039754 DOI: 10.5946/ce.2020.019-iden] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 03/23/2020] [Indexed: 11/24/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a progressive disease of the bile ducts that usually results in chronic liver disease often requiring liver transplantation. Endoscopy remains crucial to the care of these patients, although magnetic resonance cholangiopancreatography has replaced endoscopic retrograde cholangiopancreatography (ERCP) as the primary imaging modality for diagnosis. For detection of dysplasia or cholangiocarcinoma, ERCP with intraductal sampling remains compulsory. Moreover, dominant strictures play an important part in the disease development, and management by balloon dilatation or stenting could contribute to long-term prognosis. In addition, endoscopy offers management for adverse events such as bile leaks and anastomotic strictures after liver transplantation. Finally, the special phenotype of inflammatory bowel disease associated with PSC as well as the frequent occurrence of portal hypertension mandates close follow-up with colonoscopy and upper endoscopy. With the emergence of novel techniques, the endoscopist remains a key member of the multidisciplinary team caring for PSC patients.
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Affiliation(s)
- Purnima Bhat
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra, Australia.,College of Health and Medicine, Australian National University, Canberra, Australia
| | - Lars Aabakken
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.,Faculty of Medicine, University of Oslo, Oslo, Norway
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18
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Romano C, Esposito S, Ferrara R, Cuomo G. Choosing the most appropriate biologic therapy for Crohn’s disease according to concomitant extra-intestinal manifestations, comorbidities, or physiologic conditions. Expert Opin Biol Ther 2019; 20:49-62. [PMID: 31690126 DOI: 10.1080/14712598.2020.1689953] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Ciro Romano
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Sergio Esposito
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Roberta Ferrara
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
| | - Giovanna Cuomo
- Division of Internal Medicine, Department of Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Naples, Italy
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19
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Chascsa DM, Lindor KD. Cancer risk, screening and surveillance in primary sclerosing cholangitis. MINERVA GASTROENTERO 2019; 65:214-228. [PMID: 31220911 DOI: 10.23736/s1121-421x.19.02586-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.
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Affiliation(s)
- David M Chascsa
- Departments of Gastroenterology and Hepatology and Transplant Center, Mayo Clinic, Phoenix, AZ, USA -
| | - Keith D Lindor
- Office of University Provost, Arizona State University, Phoenix, AZ, USA
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20
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Stokkeland K, Höijer J, Bottai M, Söderberg-Löfdal K, Bergquist A. Statin Use Is Associated With Improved Outcomes of Patients With Primary Sclerosing Cholangitis. Clin Gastroenterol Hepatol 2019; 17:1860-1866.e1. [PMID: 30448601 DOI: 10.1016/j.cgh.2018.11.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Revised: 10/09/2018] [Accepted: 11/02/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS There is increasing evidence that statins can benefit patients with chronic liver diseases, but their effects have not been studied in patients with primary sclerosing cholangitis (PSC). We performed a nationwide study in Sweden to determine the effects of exposure to drugs, including statins, in patients with PSC. METHODS We studied a population-based cohort of patients in Sweden with PSC and concomitant ulcerative colitis or Crohn's disease from 2005 through 2014 (n = 2914), followed through 2016. We collected analyzed data from the patient register, the prescribed drug register, the death certificate register and the cancer register. We calculated risk or death, liver transplantation, bleeding of esophageal varices, and cancer in relation to drug exposure. RESULTS The mean age of patients at the time of diagnosis with PSC was 41.4 years (inter-quartile range [IQR], 25.6-56.1 years). The total follow-up time was 11769 person-years, during which 3.4% of patients received liver transplants and 19.9% died. Proportions of patients exposed to drugs were: ursodeoxycholic acid, 60.2%; 5-aminosalicylic acid, 74.4%; azathioprine or mercaptopurins, 33.7%; and statins, 13.9%. Statin use was associated with a reduced risk of all-cause mortality (hazard ratio [HR], 0.68; 95% CI, 0.54-0.88) and death or liver transplantation (HR, 0.50; 95% CI, 0.28-0.66). Use of azathioprine was also associated with reduced mortality (HR, 0.66; 95% CI, 0.52-0.84) and risk of death or liver transplantation (HR, 0.65; 95% CI, 0.50-0.83). Exposure to ursodeoxycholic acid did not affect mortality (HR, 1.04; 95% CI, 0.87-1.25). CONCLUSION In a population-based cohort of patients in Sweden with PSC, we associated use of statins and azathioprine with decreased risks of death and death or liver transplantation. Exposure to ursodeoxycholic acid was not associated with reduced mortality.
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Affiliation(s)
- Knut Stokkeland
- Department of Medicine, Visby Hospital, Visby, Sweden; Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Höijer
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Matteo Bottai
- Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Karin Söderberg-Löfdal
- Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge, Unit of Gastroenterology and Rheumatology, Karolinska Institutet, Stockholm, Sweden; Division of Hepatology, Department of Upper GI Diseases, Karolinska University Hospital, Stockholm, Sweden.
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21
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Shah SC, Glass J, Giustino G, Hove JRT, Castaneda D, Torres J, Kumar A, Elman J, Ullman TA, Itzkowitz SH. Statin Exposure Is Not Associated with Reduced Prevalence of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease. Gut Liver 2019; 13:54-61. [PMID: 30400722 PMCID: PMC6346999 DOI: 10.5009/gnl18178] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2018] [Revised: 06/29/2018] [Accepted: 07/07/2018] [Indexed: 12/21/2022] Open
Abstract
Background/Aims Statins have been postulated to lower the risk of colorectal neoplasia. No studies have examined any possible chemopreventive effect of statins in patients with inflammatory bowel disease (IBD) undergoing colorectal cancer (CRC) surveillance. This study examined the association of statin exposure with dysplasia and CRC in patients with IBD undergoing dysplasia surveillance colonoscopies. Methods A cohort of patients with IBD undergoing colonoscopic surveillance for dysplasia and CRC at a single academic medical center were studied. The inclusion criteria were IBD involving the colon for 8 years (or any colitis duration if associated with primary sclerosing cholangitis [PSC]) and at least two colonoscopic surveillance exams. The exclusion criteria were CRC or high-grade dysplasia (HGD) prior to or at enrollment, prior colectomy, or limited (<30%) colonic disease. The primary outcome was the frequency of dysplasia and/or CRC in statin-exposed versus nonexposed patients. Results A total of 642 patients met the inclusion criteria (57 statin-exposed and 585 nonexposed). The statin-exposed group had a longer IBD duration, longer follow-up period, and more colonoscopies but lower inflammatory scores, less frequent PSC and less use of thiopurines and biologics. There were no differences in low-grade dysplasia, HGD, or CRC development during the follow-up period between the statin-exposed and nonexposed groups (21.1%, 5.3%, 1.8% vs 19.2%, 2.9%, 2.9%, respectively). Propensity score analysis did not alter the overall findings. Conclusions In IBD patients undergoing surveillance colonoscopies, statin use was not associated with reduced dysplasia or CRC rates. The role of statins as chemopreventive agents in IBD remains controversial.
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Affiliation(s)
- Shailja C Shah
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.,The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jason Glass
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Gennaro Giustino
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joren R Ten Hove
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Daniel Castaneda
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Joana Torres
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.,Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Akash Kumar
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Jordan Elman
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Thomas A Ullman
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven H Itzkowitz
- The Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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22
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Abstract
Hepatobiliary disorders are commonly encountered in patients with inflammatory bowel disease (IBD). Although primary sclerosing cholangitis is the stereotypical hepatobiliary disorder associated with IBD, other diseases, including autoimmune hepatitis and nonalcoholic fatty liver disease, also are encountered in this population. Several agents used for treatment of IBD may cause drug-induced liver injury, although severe hepatotoxicity occurs infrequently. Furthermore, reactivation of hepatitis B virus infection may occur in patients with IBD treated with systemic corticosteroids and biologic agents.
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Affiliation(s)
- Mahmoud Mahfouz
- Department of Internal Medicine, Mount Sinai Medical Center, 4300 Alton Road, Suite 301, Miami Beach, FL 33140, USA
| | - Paul Martin
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA.
| | - Andres F Carrion
- Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, 1120 Northwest 14 Street #1115, Miami, FL 33136, USA
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23
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Greuter T, Vavricka SR. Extraintestinal manifestations in inflammatory bowel disease - epidemiology, genetics, and pathogenesis. Expert Rev Gastroenterol Hepatol 2019; 13:307-317. [PMID: 30791773 DOI: 10.1080/17474124.2019.1574569] [Citation(s) in RCA: 120] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder, primarily of, but not restricted to the gut. Extraintestinal manifestations (EIMs) are frequently observed and involve the joints, eyes, hepatobiliary tract, and skin. Areas covered: In this review, we discuss classical EIM focusing on epidemiology, genetics, and pathogenesis, highlighting recent advances in the understanding of EIM. We further discuss treatment-induced immunological phenomena, which are increasingly recognized and might challenge IBD-treating physicians in the era of biological treatment. Expert opinion: EIM considerably contributes to morbidity and mortality. Genetic studies have revealed a common genetic background between EIM and IBD and among specific EIM. Identified protein interactions have been shown to cluster in shared biological pathways. However - despite these recent advances - pathogenesis of EIM is at best partially understood. Several pathogenic mechanisms have been proposed such as upregulation of tumor necrosis factor, aberrant lymphocyte homing, and cross-reactive antigen presentation. It still remains unclear whether EIM is a direct result of the inflammatory process in the gut or rather a consequence of a shared genetic background leading to dysfunctional immune responses to environmental stimuli. Exploration and understanding of EIM genetics and pathophysiology will pave the road for better and more efficacious treatment options in the future.
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Affiliation(s)
- Thomas Greuter
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland
| | - Stephan R Vavricka
- a Department of Gastroenterology and Hepatology , University Hospital Zurich , Zurich , Switzerland.,b Center for Gastroenterology and Hepatology , Zurich , Switzerland
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24
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Stavsky J, Maitra R. The Synergistic Role of Diet and Exercise in the Prevention, Pathogenesis, and Management of Ulcerative Colitis: An Underlying Metabolic Mechanism. Nutr Metab Insights 2019; 12:1178638819834526. [PMID: 30911221 PMCID: PMC6425530 DOI: 10.1177/1178638819834526] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 02/08/2019] [Indexed: 12/18/2022] Open
Abstract
Ulcerative colitis (UC) is a biologically complex condition characterized by chronic, relapsing inflammation of the gastrointestinal tract. The relative incidence of this debilitating condition is increasing and sociologically damaging outcomes are a continued reality. Several etiological theories for UC are currently under investigation, spanning between genetic and environmental determinants. From an environmental perspective, previous literature reviews have demonstrated the independent effectiveness of specific diet and exercise patterns in modifying UC immuno-pathophysiology. This article explores the synergistic role of diet and aerobic exercise in the prevention, pathogenesis, and management of UC in the context of recent immunological research. Through a unifying mechanism-that is, microbial influence of colonic inflammation and immuno-pathophysiology-the simultaneous reduction of pro-inflammatory dietary sulfurous amino acid intake (ie methionine, cysteine, homocysteine, and taurine) and the upregulation of aerobic exercise frequency (which spurs the colonization of anti-inflammatory butyrate, acetate, and propionate producing microbial taxa) demonstrate the clinical efficacy of incorporating both diet and exercise modifications for UC prevention and management through pathogenic alterations.
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Affiliation(s)
- Jonah Stavsky
- Department of Biology, Yeshiva University, New York, NY, USA
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25
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Fung BM, Lindor KD, Tabibian JH. Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies. World J Gastroenterol 2019; 25:659-671. [PMID: 30783370 PMCID: PMC6378537 DOI: 10.3748/wjg.v25.i6.659] [Citation(s) in RCA: 65] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 01/10/2019] [Accepted: 01/15/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M Fung
- UCLA-Olive View Internal Medicine Residency Program, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - Keith D Lindor
- Office of the University Provost, Arizona State University, Phoenix, AZ 85004, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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Jang HJ, Kang B, Choe BH. The difference in extraintestinal manifestations of inflammatory bowel disease for children and adults. Transl Pediatr 2019; 8:4-15. [PMID: 30881893 PMCID: PMC6382501 DOI: 10.21037/tp.2019.01.06] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Extraintestinal manifestations (EIMs) are frequently observed in adult and pediatric patients with inflammatory bowel disease (IBD). The most common EIMs involve the joints, skin, and eyes, but they can affect various organs and result in significant morbidity. Since EIMs can appear years before the diagnosis of IBD is made, clinicians should be aware of their various manifestations to help decrease diagnostic delay of IBD and establish appropriate treatment plans.
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Affiliation(s)
- Hyo-Jeong Jang
- Department of Pediatrics, Keimyung University School of Medicine, Daegu, South Korea
| | - Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Byung-Ho Choe
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea
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27
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Weinberg EM, Reddy KR. Editorial: leave it unhooked? Possible benefits of ileostomy over ileal-pouch-anal anastomosis in patients with ulcerative colitis and primary sclerosing cholangitis in the setting of liver transplantation. Aliment Pharmacol Ther 2018; 48:581-582. [PMID: 30156320 DOI: 10.1111/apt.14896] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- E M Weinberg
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - K R Reddy
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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28
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Yang BR, Choi NK, Kim MS, Chun J, Joo SH, Kim H, Lee J. Prevalence of extraintestinal manifestations in Korean inflammatory bowel disease patients. PLoS One 2018; 13:e0200363. [PMID: 29990326 PMCID: PMC6039042 DOI: 10.1371/journal.pone.0200363] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Accepted: 06/25/2018] [Indexed: 12/18/2022] Open
Abstract
Background The prevalence of inflammatory bowel disease (IBD) in South Korea is increasing. Although extraintestinal manifestations (EIMs) are an important factor in the clinical outcomes of IBD patients, EIMs have not yet been investigated in Korea. Thus, we conducted a cross-sectional study to assess the prevalence of EIMs in Korean IBD patients. Methods The 2014 claims data from the National Health Insurance System (NHIS) of Korea were used. IBD patients were identified by codes for Crohn disease (CD) and ulcerative colitis (UC) in the NHIS registration system for rare or intractable diseases. International Classification of Diseases, Tenth Edition codes were used to identify EIM cases. To estimate the prevalence of EIMs in the general population of Korea, we used national sample data. Standardized prevalence ratios (SPRs) were calculated to compare the prevalence rates of EIMs among IBD patients to those among the general population of Korea. Results A total of 13,925 CD patients and 29,356 UC patients were identified. CD and UC patients were different in terms of demographics and utilization of medication. Among the 17 EIMs investigated, pyoderma gangrenosum, osteomalacia, Sweet syndrome, and scleritis were observed in very few patients. The SPRs were greater than 1 for all EIMs. Aphthous stomatitis, rheumatoid arthritis, and osteoporosis were highly prevalent in both CD and UC patients, but the SPRs of the EIMs were not high. Conclusion The study confirmed that EIMs are more prevalent among IBD patients than among the general population of Korea. The prevalence of EIMs in IBD patients suggests the need for greater attention and effort in clinical practice.
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Affiliation(s)
- Bo Ram Yang
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
| | - Nam-Kyong Choi
- Department of Health Convergence, Ewha Womans University, Seoul, Republic of Korea
| | - Mi-Sook Kim
- Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Republic of Korea
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jaeyoung Chun
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Sang Hyun Joo
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Hyesung Kim
- Medical Affairs, Janssen Korea, Seoul, Republic of Korea
| | - Joongyub Lee
- School of Medicine, Inha University, Incheon, Republic of Korea
- Department of Prevention and Management, Inha University Hospital, Incheon, Republic of Korea
- * E-mail:
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Tabibian JH, Bowlus CL. WITHDRAWN: Primary sclerosing cholangitis: A review and update. LIVER RESEARCH 2018. [DOI: 10.1016/j.livres.2017.12.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Lampinen M, Fredricsson A, Vessby J, Martinez JF, Wanders A, Rorsman F, Carlson M. Downregulated eosinophil activity in ulcerative colitis with concomitant primary sclerosing cholangitis. J Leukoc Biol 2018; 104:173-183. [DOI: 10.1002/jlb.3ma0517-175r] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 02/26/2018] [Accepted: 03/11/2018] [Indexed: 12/30/2022] Open
Affiliation(s)
- Maria Lampinen
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
| | - Annika Fredricsson
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
| | - Johan Vessby
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
| | - Johana Fernandez Martinez
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
| | - Alkwin Wanders
- Department of Medical Biosciences; Umeå University; Umeå Sweden
| | - Fredrik Rorsman
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
| | - Marie Carlson
- Department of Medical Sciences; Gastroenterology Research Group; University Hospital; Uppsala Sweden
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Chang M, Chang L, Chang HM, Chang F. Intestinal and Extraintestinal Cancers Associated With Inflammatory Bowel Disease. Clin Colorectal Cancer 2018; 17:e29-e37. [DOI: 10.1016/j.clcc.2017.06.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2017] [Revised: 06/18/2017] [Accepted: 06/21/2017] [Indexed: 12/16/2022]
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Rao BB, Lashner B, Kowdley KV. Reviewing the Risk of Colorectal Cancer in Inflammatory Bowel Disease After Liver Transplantation for Primary Sclerosing Cholangitis. Inflamm Bowel Dis 2018; 24:269-276. [PMID: 29361103 DOI: 10.1093/ibd/izx056] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Indexed: 02/07/2023]
Abstract
The presence of concomitant primary sclerosing cholangitis (PSC) with inflammatory bowel disease (IBD) represents a distinct disease phenotype that carries a higher risk of colorectal cancer (CRC) than the average IBD patient. Given that liver transplantation (LT) is the only treatment that offers a survival benefit in PSC patients with hepatic dysfunction, management decisions in IBD patients' post-LT for PSC are frequently encountered. One such consideration is the risk of CRC in this immunosuppressed cohort. With most studies showing an increased risk of CRC post-LT in these IBD patients, a closer look at the associated risk factors of CRC and the adopted surveillance strategies in this subset of patients is warranted. Low-dose ursodeoxycholic acid has shown a potential chemopreventive effect in PSC-IBD patients pre-LT; however, a favorable effect remains to be seen in post-LT group. Also, further studies are necessary to assess the benefit of 5 aminosalicylate therapy. Annual surveillance colonoscopy in the post-LT period is recommended for PSC-IBD patients subset given their high risk for CRC.
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Affiliation(s)
- Bhavana Bhagya Rao
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Bret Lashner
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic Foundation, Cleveland, Ohio
| | - Kris V Kowdley
- Liver Care Network and Organ Care Research, Swedish Medical Center, Seattle, Washington
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Abstract
Primary sclerosing cholangitis (PSC) is a rare, chronic, cholestatic liver disease of uncertain etiology characterized biochemically by cholestasis and histologically and cholangiographically by fibro-obliterative inflammation of the bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and/or hepatobiliary cancer, though the disease course can be highly variable. Despite clinical trials of numerous pharmacotherapies over several decades, safe and effective medical therapy remains to be established. Liver transplantation is an option for select patients with severe complications of PSC, and its outcomes are generally favorable. Periodic surveillance testing for pre- as well as post-transplant patients is a cornerstone of preventive care and health maintenance. Here we provide an overview of PSC including its epidemiology, etiopathogenesis, clinical features, associated disorders, surveillance, and emerging potential therapies.
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Affiliation(s)
- James H. Tabibian
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
- Division of Gastroenterology, Olive View-UCLA Medical Center, Sylmar, CA, USA
| | - Christopher L. Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis, Sacramento, CA, USA
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34
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Cardile S, Alterio T, Candusso M, Pietrobattista A, Liccardo D, Basso MS, Papadatou B, Bracci F, Knafelz D, Torre G. Autoimmune liver diseases and inflammatory bowel diseases in children: current issues and future perspectives. Scand J Gastroenterol 2017; 52:662-667. [PMID: 28281846 DOI: 10.1080/00365521.2017.1298833] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases (IBDs) represent a group of intestinal disorders with a chronic and relapsing inflammation of the gut, and with a potential risk of systemic involvement of other organs and systems. Over the pediatric age, an incidence higher than 20% of developing extraintestinal manifestation during follow-up has been reported. The liver and the biliary system are frequently involved, and primary sclerosing cholangitis (PSC) is the most predominant entity with an incidence rate of 6.4-7.8% in children. PSC recognizes a multifactorial pathogenesis, and so far a not fully known mechanism for this association. The peculiar phenotype and the distinct clinical course of patients with IBD and PSC-associated make this 'linkage' an attractive study model to better understand mechanisms underlying these diseases. Approaching to these patients is complex and multidisciplinary, and a unique therapeutic strategy has not been standardized yet. New medications are being studied; however, further studies are needed to fully understand the pathogenesis and to improve the care of these patients. The aim of this paper is to review the recent literature regarding hepatobiliary involvement in IBD patients, with particular attention to PSC, and to provide the latest information for a correct diagnosis and appropriate management.
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Affiliation(s)
- Sabrina Cardile
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Tommaso Alterio
- b Department of Pediatrics , University of Messina , Messina , Italy
| | - Manila Candusso
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Andrea Pietrobattista
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Daniela Liccardo
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Maria Sole Basso
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Bronislava Papadatou
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Fiammetta Bracci
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Daniela Knafelz
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Giuliano Torre
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
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Primary sclerosing cholangitis is protective against nonalcoholic fatty liver disease in inflammatory bowel disease. Hum Pathol 2017; 69:55-62. [PMID: 28970141 DOI: 10.1016/j.humpath.2017.09.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Revised: 09/17/2017] [Accepted: 09/22/2017] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) occurs with higher prevalence in patients with inflammatory bowel disease (IBD) relative to the general population, and susceptibility is related to the metabolic syndrome, as well as higher prevalence of bowel resection and gut microbiotal factors. Liver complications, including NAFLD and primary sclerosing cholangitis (PSC), contribute to treatment and prognosis of patients with IBD. However, the potential interplay of NAFLD and PSC is not well understood. We retrospectively assessed severity of steatosis and steatohepatitis in liver specimens from 49 patients with IBD only, 44 with IBD and comorbid PSC, and 30 with IBD and PSC after liver transplantation. Patients with IBD had higher prevalence of at least grade 1 steatosis (59%) than IBD and PSC (11%), or IBD and PSC posttransplant (3%) (P < .001). The average severity of steatosis was 25% ± 8% (95% confidence interval) for IBD only, 3% ± 1% for comorbid IBD and PSC, and 1% ± 1% for IBD and PSC posttransplant (P < .001). Steatohepatitis was significantly higher in IBD only (12%) than in IBD and PSC ± transplant (0%) (P = .01). Despite these differences in susceptibility to NAFLD, the 3 populations had statistically indistinguishable average body mass index and total cholesterol and prevalence of hypertension, diabetes, and alcohol use. Multivariate regression modeling revealed body mass index, hypertension, and diabetes as significant correlates to NAFLD severity in all studied populations. In conclusion, patients with comorbid IBD and PSC have significantly less susceptibility to NAFLD than those with IBD alone, despite similar prevalence of major NAFLD risk factors.
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Risk Factors and Outcomes of De Novo Cancers (Excluding Nonmelanoma Skin Cancer) After Liver Transplantation for Primary Sclerosing Cholangitis. Transplantation 2017; 101:1859-1866. [PMID: 28272287 DOI: 10.1097/tp.0000000000001725] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with primary sclerosing cholangitis (PSC) may be at higher risk of malignancy after liver transplantation (LT) compared to other LT recipients. We aimed to determine the cumulative incidence of/risk factors for long-term cancer-related mortality in patients with PSC after LT. METHODS All adult patients underwent LT for PSC without cholangiocarcinoma from 1984 to 2012, with follow-up through June 2015. We estimated cumulative incidence, risk factors, and mortality from de novo malignancies after LT. RESULTS Two hundred ninety-three patients were identified (mean [SD] age, 47 [12] years; 63.3% males; 2.4% smoking at LT). Over a median of 11.5 years (range, 6.4-18.6 years), 64 patients (21.8%) developed 73 nonskin cancers, including 46 solid-organ cancers (renal, 11; colorectal, 11; prostate, 7; breast, 5; pancreas, 5; ovarian/endometrial/vulvar cancers, 3; and de novo cholangiocarcinoma, 4). Twenty-two patients developed hematologic malignancies (posttransplant lymphoproliferative diseases, 18; Hodgkin disease, 2; and myelodysplastic syndrome, 2). Five patients developed melanoma. The 1-, 5-, 10-, and 20-year cumulative incidences of cancer were 2.1%, 8.6%, 18.7%, and 27%, respectively. Mortality of patients with PSC who developed cancer was higher than that of patients with PSC without cancer (hazard ratio, 2.2; P < 0.01). On multivariate analysis, recipient's age and elevated pre-LT international normalized ratio were associated with increased risk of de novo (nonskin) malignancy. CONCLUSION The 10-year cumulative risk of cancer after LT for advanced-stage PSC was 18.7%, with posttransplant lymphoproliferative diseases, colorectal cancer, and renal cell cancer being the most common. Post-LT de novo nonskin cancer decreased overall posttransplant survival. Only recipient's age and elevated international normalized ratio at LT were associated with increased nonskin cancer risk.
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37
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Horsley-Silva JL, Rodriguez EA, Franco DL, Lindor KD. An update on cancer risk and surveillance in primary sclerosing cholangitis. Liver Int 2017; 37:1103-1109. [PMID: 28028930 DOI: 10.1111/liv.13354] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 12/20/2016] [Indexed: 02/13/2023]
Abstract
Malignancy represents substantial morbidity and mortality in patients with primary sclerosing cholangitis (PSC). This subset of patients has been proven to be at increased risk for developing cholangiocarcinoma, gallbladder carcinoma and colorectal cancer in those with overlapping inflammatory bowel disease. Herein, we review the prevalence of these malignancies and recommend screening tools and current knowledge to reduce the disease burden in this population. Cholangiocarcinoma is the most dominant malignancy affecting PSC patients, with a lifetime risk ranging from 5% to 20%. We advocate for serial US or MRI/MRCP and CA 19-9 to screen for cholangiocarcinoma. Gallbladder cancer has a lifetime risk around 2% in this population and we agree with annual imaging for lesions as recommended by national guidelines. Patients with PSC and concomitant IBD are at increased risk of colorectal carcinoma from time of diagnosis and therefore should likely undergo annual surveillance. The low rates of hepatocellular cancer and pancreatic cancer indicate surveillance for these malignancies is less advantageous.
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Affiliation(s)
| | | | - Diana L Franco
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.,College of Health Solutions, Arizona State University, Phoenix, AZ, USA
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38
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Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, Färkkilä M, Fickert P, Hirschfield GM, Laghi A, Marzioni M, Fernandez M, Pereira SP, Pohl J, Poley JW, Ponsioen CY, Schramm C, Swahn F, Tringali A, Hassan C. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. J Hepatol 2017; 66:1265-1281. [PMID: 28427764 DOI: 10.1016/j.jhep.2017.02.013] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 02/14/2017] [Indexed: 02/06/2023]
Abstract
This guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations.
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Preoperative Extraintestinal Manifestations Associated with Chronic Pouchitis in Japanese Patients with Ulcerative Colitis After Ileal Pouch-anal Anastomosis: A Retrospective Study. Inflamm Bowel Dis 2017; 23:1019-1024. [PMID: 28346273 DOI: 10.1097/mib.0000000000001094] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Pouchitis is a major problem after ileal pouch-anal anastomosis in patients with ulcerative colitis. Chronic pouchitis is particularly troublesome. This study aimed to identify risk factors for the development of chronic pouchitis in a Japanese population. METHODS We retrospectively reviewed 100 patients who underwent pouchoscopy for a functioning ileal pouch. The diagnosis of pouchitis was made according to the modified pouchitis disease activity index. The incidence of pouchitis was estimated using the Kaplan-Meier curve, and Cox regression analysis was used to identify risk factors for the development of chronic pouchitis. RESULTS Twenty-two patients developed pouchitis; 12 of them had chronic pouchitis. The incidences of chronic pouchitis were 3.3%, 7.6%, and 16.6% at 2, 5, and 10 years, respectively, after the pouch operation. The incidence of pouchitis was significantly higher in patients with preoperative extraintestinal manifestations (EIMs) than in those without (log-rank test, P = 0.002 and P = 0.005 for overall and chronic pouchitis, respectively). Cox regression analysis revealed that the presence of extraintestinal manifestations was an independent risk factor for the development of overall (hazard ratio: 4.48, 95% confidence interval, 1.77-11.30, P = 0.002) and chronic (hazard ratio: 5.81, 95% confidence interval, 1.67-20.23, P = 0.006) pouchitis. CONCLUSIONS The presence of preoperative extraintestinal manifestations was found to be an independent risk factor for the development of overall and chronic pouchitis.
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40
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Kim S, Lee BH, Zhang X, Park JW, Lee S, Lee H. Adjunctive herbal medicine therapy for inflammatory bowel disease: A systematic review and meta-analysis. Eur J Integr Med 2017. [DOI: 10.1016/j.eujim.2017.03.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Olpin JD, Sjoberg BP, Stilwill SE, Jensen LE, Rezvani M, Shaaban AM. Beyond the Bowel: Extraintestinal Manifestations of Inflammatory Bowel Disease. Radiographics 2017; 37:1135-1160. [PMID: 28548906 DOI: 10.1148/rg.2017160121] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing immune-mediated inflammation of the gastrointestinal tract. IBD includes two major disease entities: Crohn disease and ulcerative colitis. Imaging plays an important role in the diagnosis and surveillance of these complex disorders. Computed tomographic and magnetic resonance enterographic techniques have been refined in recent years to provide a superb means of evaluating the gastrointestinal tract for suspected IBD. Although the intestinal imaging manifestations of IBD have been extensively discussed in the radiology literature, extraintestinal imaging manifestations of IBD have received less attention. Multiple extraintestinal manifestations may be seen in IBD, including those of gastrointestinal (hepatobiliary and pancreatic), genitourinary, musculoskeletal, pulmonary, cardiac, ocular, and dermatologic disorders. Although many associations between IBD and extraintestinal organ systems have been well established, other associations have not been fully elucidated. Some extraintestinal disorders may share a common pathogenesis with IBD. Other extraintestinal disorders may occur as a result of unintended treatment-related complications of IBD. Although extraintestinal disorders within the abdomen and pelvis may be well depicted with cross-sectional enterography, other musculoskeletal and thoracic disorders may be less evident with such examinations and may warrant further investigation with additional imaging examinations or may be readily apparent from the findings at physical examination. Radiologists involved in the interpretation of IBD imaging examinations must be aware of potential extraintestinal manifestations, to provide referring clinicians with an accurate and comprehensive profile of patients with these complex disorders. © RSNA, 2017.
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Affiliation(s)
- Jeffrey D Olpin
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
| | - Brett P Sjoberg
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
| | - Sarah E Stilwill
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
| | - Leif E Jensen
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
| | - Maryam Rezvani
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
| | - Akram M Shaaban
- From the Department of Diagnostic Radiology (J.D.O., S.E.S., L.E.J., M.R., A.M.S.), University of Utah, 30 North 1900 East, #1A71, Salt Lake City, UT 84132; and the Department of Diagnostic Radiology, University of Wisconsin, Madison, Wis (B.P.S.)
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Diagnostic autoantibodies for autoimmune liver diseases. Clin Transl Immunology 2017; 6:e139. [PMID: 28690845 PMCID: PMC5493583 DOI: 10.1038/cti.2017.14] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2016] [Revised: 03/22/2017] [Accepted: 03/22/2017] [Indexed: 12/17/2022] Open
Abstract
Autoimmune liver diseases are conditions of low prevalence that comprise the triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and primary sclerosing cholangitis and their poorly characterised overlapping syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and primary biliary cholangitis but not with primary sclerosing cholangitis. Autoantibodies are useful disease markers that facilitate early diagnosis of autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic intervention to prevent progression to liver cirrhosis and associated complications. Adult onset type 1 autoimmune hepatitis is associated with F-actin reactive smooth muscle autoantibody, antinuclear autoantibody in 60% of patients, and autoantibody to SLA/LP in 15–20%. Juvenile onset type 2 autoimmune hepatitis is associated with LKM-1 and LC-1 autoantibodies. Primary biliary cholangitis is associated with a mitochondria-associated autoantibody designated M2 in >90% of patients and with disease-specific antinuclear autoantibodies in 50% that bind to antigens in the nuclear core complex and in multiple nuclear dots. Autoantibodies to the nuclear core complex target gp210, nucleoporin p62 and nuclear lamin B receptor. Autoantibodies to multiple nuclear dots target Sp100 and PML antigens. Liver autoantibodies in asymptomatic patients with normal liver function may precede the subsequent development of overt autoimmune liver disease. For routine diagnostic immunology laboratories, initial screening for liver autoantibodies by immunofluorescence remains the method of choice with confirmation for reactivity with their target antigen by enzyme-linked immunosorbent assay (ELISA) or line blot when required.
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Gidwaney NG, Pawa S, Das KM. Pathogenesis and clinical spectrum of primary sclerosing cholangitis. World J Gastroenterol 2017; 23:2459-2469. [PMID: 28465630 PMCID: PMC5394509 DOI: 10.3748/wjg.v23.i14.2459] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Revised: 01/21/2017] [Accepted: 03/20/2017] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a disease of the biliary tract, which has been documented in the literature since 1867. This disease has a strong predilection for affecting men and can be seen in individuals as young as 2 years of age. PSC has a strong associated with inflammatory bowel disease, more commonly with ulcerative colitis, and is also part of the clinical spectrum of IgG4-related diseases. Small-duct PSC, a variant of PSC, also has an association with inflammatory bowel disease. The exact pathogenesis of PSC is not well understood at present, however, is likely a combination of a genetic predisposition with alteration of the molecular structure of the gut. Abnormal serum liver chemistry and presence of certain autoimmune markers are usually the first indicators leading to a diagnosis of PCS, however, these may often be normal in early stages of this disease. The diagnosis is made by cholangiography, which is now considered the gold standard. PSC is a known pre-malignant condition. Such patients have an increased risk of developing cholangiocarcinoma, gallbladder neoplasia, and colon cancer. Many new treatment modalities have emerged in the recent past, including anti-tumor necrosis factor- α and anti-integrins; however, liver transplantation is the only known cure for PSC. Despite past and present research, PSC remains an enigmatic biliary disease with few viable treatment options.
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Jendrek ST, Gotthardt D, Nitzsche T, Widmann L, Korf T, Michaels MA, Weiss KH, Liaskou E, Vesterhus M, Karlsen TH, Mindorf S, Schemmer P, Bär F, Teegen B, Schröder T, Ehlers M, Hammers CM, Komorowski L, Lehnert H, Fellermann K, Derer S, Hov JR, Sina C. Anti-GP2 IgA autoantibodies are associated with poor survival and cholangiocarcinoma in primary sclerosing cholangitis. Gut 2017; 66:137-144. [PMID: 27406039 DOI: 10.1136/gutjnl-2016-311739] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2016] [Revised: 06/19/2016] [Accepted: 06/20/2016] [Indexed: 12/14/2022]
Abstract
OBJECTIVE Pancreatic autoantibodies (PABs), comprising antibodies against glycoprotein 2 (anti-GP2), are typically associated with complicated phenotypes in Crohn's disease, but have also been observed with variable frequencies in patients with UC. In a previous study, we observed a high frequency of primary sclerosing cholangitis (PSC) in patients with anti-GP2-positive UC. We therefore aimed to characterise the role of anti-GP2 in PSC. DESIGN In an evaluation phase, sera from 138 well-characterised Norwegian patients with PSC were compared with healthy controls (n=52), and patients with UC without PSC (n=62) for the presence of PABs by indirect immunofluorescence. Further, 180 German patients with PSC served as a validation cohort together with 56 cases of cholangiocarcinoma without PSC, 20 of secondary sclerosing cholangitis (SSC) and 18 of autoimmune hepatitis. RESULTS Anti-GP2 IgA specifically occurred at considerable rates in large bile duct diseases (cholangiocarcinoma=36%, PSC and SSC about 50%). In PSC, anti-GP2 IgA consistently identified patients with poor survival during follow-up (Norwegian/German cohort: p Log Rank=0.016/0.018). Anti-GP2 IgA was associated with the development of cholangiocarcinoma in both PSC cohorts, yielding an overall OR of cholangiocarcinoma in patients with anti-GP2 IgA-positive PSC of 5.0 (p=0.001). Importantly, this association remained independent of disease duration, bilirubin level and age. CONCLUSIONS Anti-GP2 IgA can be hypothesised as a novel marker in large bile duct diseases. In particular, in PSC, anti-GP2 IgA identified a subgroup of patients with severe phenotype and poor survival due to cholangiocarcinoma. Anti-GP2 IgA may therefore be a clinically valuable tool for risk stratification in PSC.
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Affiliation(s)
- Sebastian Torben Jendrek
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.,Institute for Anatomy, University of Lübeck, Lübeck, Germany
| | - Daniel Gotthardt
- Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Thomas Nitzsche
- Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany
| | - Laila Widmann
- Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Tobias Korf
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Maike Anna Michaels
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Karl-Heinz Weiss
- Section of Liver Transplantation, Medical Department IV, University Hospital Heidelberg, Heidelberg, Germany
| | - Evaggelia Liaskou
- Centre for Liver Research and NIHR Birmingham Liver Biomedical Research Unit, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Mette Vesterhus
- Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
| | - Tom Hemming Karlsen
- Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway
| | - Swantje Mindorf
- Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany
| | - Peter Schemmer
- Department of General, Visceral and Transplant Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Florian Bär
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Bianca Teegen
- Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany
| | - Torsten Schröder
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany.,Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
| | - Marc Ehlers
- Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany
| | | | - Lars Komorowski
- Institute for Experimental Immunology, Euroimmun Corp., Lübeck, Germany
| | - Hendrik Lehnert
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Klaus Fellermann
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Stefanie Derer
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
| | - Johannes Roksund Hov
- Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Division of Cancer Medicine, Surgery and Transplantation, Research Institute of Internal Medicine and Section of Gastroenterology, Oslo University Hospital Rikshospitalet, Oslo, Norway.,Faculty of Medicine, Institute of Clinical Medicine and K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway
| | - Christian Sina
- Molecular Gastroenterology, Medical Department 1, University of Lübeck, Lübeck, Germany
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Lammert C, Vuppalanchi R. Future Therapies for Primary Sclerosing Cholangitis. PRIMARY SCLEROSING CHOLANGITIS 2017:153-166. [DOI: 10.1007/978-3-319-40908-5_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Moussata D, Boschetti G, Stefanescu C, Nancey S, Bouhnik Y, Flourie B. Isolated ileitis associated with primary sclerosing cholangitis in three patients with Crohn's disease. Scand J Gastroenterol 2016; 51:727-30. [PMID: 26806276 DOI: 10.3109/00365521.2015.1126634] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is associated with ulcerative colitis and extensive colonic involvement or ileocolitis in Crohn's disease (CD). To our knowledge, no specific report of isolated ileitis associated with PSC in CD patients has been published in CD patients. AIM AND METHODS We report three cases of patients with isolated Crohn's ileitis associated with PSC and in whom colonic inflammation was never documented. RESULTS Patients were followed up 10-23 years and each patient underwent 6-7 ileocolonoscopies: inflammation was located only in the terminal ileum, which was confirmed on surgical specimens in two patients. Small-duct PSC led to diagnosis of CD ileitis in one patient, while small and large-ducts PSC were evidenced after CD diagnosis in the other 2. PSC were regularly followed for 9-10 years. CONCLUSIONS Our three cases of PSC with isolated CD ileitis and long-term follow-up without any sign of colonic involvement argue against the concept that colonic mucosal inflammation is critical for the pathogenesis of PSC in inflammatory bowel disease.
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Affiliation(s)
- Driffa Moussata
- a Trousseau Hospital and Rabelais University, Tours , France
| | - Gilles Boschetti
- b Lyon Sud Hospital and University Claude Bernard Lyon , Pierre Béite , France
| | - Carmen Stefanescu
- b Lyon Sud Hospital and University Claude Bernard Lyon , Pierre Béite , France
| | - Stephane Nancey
- b Lyon Sud Hospital and University Claude Bernard Lyon , Pierre Béite , France
| | - Yoram Bouhnik
- c Beaujon Hospital, Assistance Publique des Hôpitaux de Paris and University Diderot , Paris , France
| | - Bernard Flourie
- b Lyon Sud Hospital and University Claude Bernard Lyon , Pierre Béite , France
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Lunder AK, Hov JR, Borthne A, Gleditsch J, Johannesen G, Tveit K, Viktil E, Henriksen M, Hovde Ø, Huppertz-Hauss G, Høie O, Høivik ML, Monstad I, Solberg IC, Jahnsen J, Karlsen TH, Moum B, Vatn M, Negård A. Prevalence of Sclerosing Cholangitis Detected by Magnetic Resonance Cholangiography in Patients With Long-term Inflammatory Bowel Disease. Gastroenterology 2016; 151:660-669.e4. [PMID: 27342213 DOI: 10.1053/j.gastro.2016.06.021] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2015] [Revised: 06/07/2016] [Accepted: 06/13/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The prevalence of primary sclerosing cholangitis (PSC) among patients with inflammatory bowel disease (IBD) is unclear. Patients with IBD might be screened for PSC using magnetic resonance cholangiography (MRC). We aimed to estimate the frequency and distribution of MRC-detected lesions that indicate PSC in patients with IBD 20 years after their initial diagnosis and to identify clinical characteristics associated with these findings. METHODS We performed a follow-up analysis of a population-based cohort of 756 patients in South-Eastern Norway diagnosed with IBD from January 1, 1990 through December 31, 1993. Of these subjects, 470 attended a follow-up evaluation 20 years later in which they were offered routine clinical blood testing and ileocolonoscopy; 322 were screened by MRC (222 with ulcerative colitis and 100 with Crohn's disease). Two radiologists independently evaluated results from the MRC examinations. RESULTS In the MRC examination, 24 patients (7.5%) were found to have PSC-like lesions; only 7 of these patients (2.2%) were known to have PSC. One patient was initially missed and 1 had small-duct PSC, so the final prevalence of PSC was 8.1%. Extensive colitis, a high prevalence of colectomy, and chronic and continuous symptoms of IBD occurred in significantly more patients with suspected PSC than without PSC (P = .029, P = .002, and P = .012, respectively). Among patients with subclinical features of PSC, the MRC progression score for PSC increased when they were re-examined after a median 3.2 years (P = .046). CONCLUSIONS Using MRC analysis of patients with long-term IBD, we found the prevalence of PSC to be around 3-fold higher than that detected based on symptoms. Sixty-five percent of patients had subclinical PSC associated with progressive IBD, with no biochemical abnormalities and mild disease, based on radiology findings. PSC appears to progress in patients with subclinical disease, but long-term outcomes are not known.
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Affiliation(s)
- Aida Kapic Lunder
- Department of Radiology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Johannes Roksund Hov
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K. G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Arne Borthne
- Department of Radiology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
| | | | | | | | - Ellen Viktil
- Department of Radiology, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Magne Henriksen
- Department of Gastroenterology, Østfold Hospital, Fredrikstad, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Innlandet Hospital, Gjøvik, Norway
| | | | - Ole Høie
- Department of Gastroenterology, Sørlandet Hospital, Arendal, Norway
| | - Marte Lie Høivik
- Department of Gastroenterology, Division of Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Iril Monstad
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Division of Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Inger Camilla Solberg
- Department of Gastroenterology, Division of Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Jørgen Jahnsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Tom Hemming Karlsen
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; K. G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | - Bjørn Moum
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Division of Medicine, Oslo University Hospital, Ullevål, Oslo, Norway
| | - Morten Vatn
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; EpiGen Institute, Akershus University Hospital, Lørenskog, Norway
| | - Anne Negård
- Department of Radiology, Akershus University Hospital, Lørenskog, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Weersma RK, Lindor KD. Shifting Paradigms: What Is the True Prevalence and Clinical Course of Primary Sclerosing Cholangitis? Gastroenterology 2016; 151:590-3. [PMID: 27590692 DOI: 10.1053/j.gastro.2016.08.046] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Rinse K Weersma
- Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
| | - Keith D Lindor
- College of Health Solutions, Arizona State University and Mayo Clinic Arizona, Phoenix, Arizona
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Dlugosz A, Barakat AM, Björkström NK, Öst Å, Bergquist A. Diagnostic yield of endomicroscopy for dysplasia in primary sclerosing cholangitis associated inflammatory bowel disease: a feasibility study. Endosc Int Open 2016; 4:E901-11. [PMID: 27540581 PMCID: PMC4988862 DOI: 10.1055/s-0042-111203] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Accepted: 06/13/2016] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND AND STUDY AIMS Primary sclerosing cholangitis associated inflammatory bowel disease (PSC-IBD) is characterized by a high risk of colorectal dysplasia. Surveillance colonoscopies with random biopsies have doubtful power for dysplasia detection. Our aim was to prospectively investigate the feasibility and efficacy of pCLE in surveillance colonoscopies in patients with PSC-IBD. PATIENTS AND METHODS Sixty-nine patients with PSC-IBD underwent colonoscopy in 2 steps. On the way from rectum to cecum, the mucosa was inspected with high definition endoscopy (HDE) and random biopsies were taken according to the standard routine. On the way from cecum to rectum, fluorescein-enhanced pCLE and chromoendoscopy were performed. Regions where random biopsies had been taken, as well as visible lesions, were examined with pCLE and targeted biopsies were taken of lesions suspicious for dysplasia. Two investigators, blinded to histology and endoscopy results, analyzed all pCLE videos off-line. RESULTS Nineteen biopsies obtained in 13 patients (17 targeted biopsies, 2 random biopsies) revealed the presence of low-grade dysplasia. Thirteen lesions with dysplasia were endoscopically visible but by using pCLE-targeted biopsies, additional endoscopically invisible dysplasias in 4 biopsies obtained from 3 patients were detected. The sensitivity, specificity, and accuracy of pCLE in predicting dysplasia were respectively 89 % (95 % CI: 65 - 98), 96 % (95 % CI: 94 - 97), and 96 % (95 % CI: 94 - 97). pCLE showed a good performance for differentiating neoplastic from non-neoplastic mucosa with negative predictive value of 99 %. CONCLUSIONS pCLE in PSC-IBD surveillance is feasible and may be a good complement to HDE. Future research should aim at elucidating whether real-time pCLE is applicable in PSC-IBD surveillance.
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Affiliation(s)
- Aldona Dlugosz
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden,Corresponding author Aldona Dlugosz, MD, PhD Karolinska Institutet, Department of MedicineKarolinska University Hospital, HuddingeCenter for Digestive DiseasesSE-14186 StockholmSweden+46 8 585 823 43+46 8 585 823 35
| | - Ammar Mohkles Barakat
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Niklas K. Björkström
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden,Department of Medicine Huddinge and Center for Infectious Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Åke Öst
- Department of Pathology Huddinge, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
| | - Annika Bergquist
- Department of Medicine Huddinge and Center for Digestive Diseases, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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Kumar A, Wheatley D, Puttanna A. Primary Sclerosing Cholangitis: Therapeutic Options and Surveillance Management. CLINICAL MEDICINE INSIGHTS. GASTROENTEROLOGY 2016; 9:25-9. [PMID: 27330336 PMCID: PMC4902039 DOI: 10.4137/cgast.s38451] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/05/2016] [Revised: 05/01/2016] [Accepted: 05/03/2016] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis is a chronic immune-mediated liver disease. Though rare, it poses several clinical concerns for the managing physician. There are currently limited therapeutic options in the management of the condition and weak evidence base behind them. Endoscopic intervention is limited to those patients with obstructing stricture-related disease, and even liver transplantation has a risk of disease recurrence. Surveillance for inflammatory bowel disorders, metabolic bone disease, and malignancy is paramount when managing such patients. This article provides an overview of the condition with further focus on current therapeutic options and guidance on surveillance management.
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Affiliation(s)
| | | | - Amar Puttanna
- University Hospital North Midlands, Stoke-on-Trent, England, UK
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