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Bloemen H, Livanos AE, Martins A, Dean R, Bravo AC, Bourgonje AR, Tankelevich M, Herb J, Cho J, Santos AA, Rodrigues CMP, Petralia F, Colombel JF, Bowlus CL, Schiano T, Torres J, Levy C, Mehandru S. Anti-integrin αvβ6 Autoantibodies are Increased in Primary Sclerosing Cholangitis Patients With Concomitant Inflammatory Bowel Disease and Correlate With Liver Disease Severity. Clin Gastroenterol Hepatol 2024:S1542-3565(24)00969-8. [PMID: 39490950 DOI: 10.1016/j.cgh.2024.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 09/13/2024] [Accepted: 10/01/2024] [Indexed: 11/05/2024]
Abstract
BACKGROUND & AIMS Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity. METHODS Four cohorts of pre-liver transplant patients with PSC were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HCs) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay. Olink inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity. RESULTS A total of 137 patients with PSC (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD), and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HCs) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared with PSC alone (P < .0001 and P < .003) and HCs (P < .0001 and P < .0001). However, anti-αvβ6 levels in PSC alone were not increased compared with HCs. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity, including alkaline phosphatase level (r = 0.32; P = .004), the revised Mayo PSC risk score (r = 0.25; P = .02), and liver stiffness measurement (r = 0.43; P = .008) after adjusting for age, gender, race/ethnicity, and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling. CONCLUSION Anti-αvβ6 autoantibodies identify a subset of patients with PSC with concomitant IBD.
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Affiliation(s)
- Hannah Bloemen
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Alexandra E Livanos
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
| | - Adrielly Martins
- Schiff Center for Liver Diseases, University of Miami Leonard M. Miller School of Medicine, Miami, Florida
| | - Richard Dean
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | | | - Arno R Bourgonje
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Michael Tankelevich
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jake Herb
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Judy Cho
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - André Anastácio Santos
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Cecília M P Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal
| | - Francesca Petralia
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Thomas Schiano
- Recanati/Miller Transplantation Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joana Torres
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal; Faculty of Medicine, Universidade de Lisboa, Lisbon, Portugal; Division of Gastroenterology, Hospital da Luz, Lisbon, Portugal
| | - Cynthia Levy
- Schiff Center for Liver Diseases, University of Miami Leonard M. Miller School of Medicine, Miami, Florida; Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida.
| | - Saurabh Mehandru
- Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
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Wang MH, Friton JJ, Raffals LE, Leighton JA, Pasha SF, Picco MF, Monroe K, Nix BD, Newberry RD, Faubion WA. Polygenic risk score predicts risk of primary sclerosing cholangitis in inflammatory bowel disease. BMJ Open Gastroenterol 2023; 10:e001141. [PMID: 37832963 PMCID: PMC10583098 DOI: 10.1136/bmjgast-2023-001141] [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: 02/28/2023] [Accepted: 09/08/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Forty distinct primary sclerosing cholangitis (PSC) genomic loci have been identified through multiancestry meta-analyses. The polygenic risk score (PRS) could serve as a promising tool to discover unique disease behaviour, like PSC, underlying inflammatory bowel disease (IBD). AIM To test whether PRS indicates PSC risk in patients with IBD. MATERIALS AND METHODS Mayo Clinic and Washington University at St Louis IBD cohorts were used to test our hypothesis. PRS was modelled through the published PSC loci and weighted with their corresponding effect size. Logistic regression was applied to predict the PSC risk. RESULTS In total, 63 (5.6%) among 1130 patients with IBD of European ancestry had PSC. Among 381 ulcerative colitis (UC), 12% had PSC; in contrast to 1.4% in 761 Crohn disease (CD). Compared with IBD alone, IBD-PSC had significantly higher PRS (PSC risk: 3.0% at the lowest PRS quartile vs 7.2% at the highest PRS quartile, Ptrend =.03). In IBD subphenotypes subgroup analysis, multivariate analysis shows that UC-PSC is associated with more extensive UC disease (OR, 5.60; p=0.002) and younger age at diagnosis (p=0.02). In CD, multivariate analysis suggests that CD-PSC is associated with colorectal cancer (OR, 50; p=0.005). CONCLUSIONS We found evidence that patients with IBD with PSC presented with a clinical course difference from that of patients with IBD alone. PRS can influence PSC risk in patients with IBD. Once validated in an independent cohort, this may help identify patients with the highest likelihood of developing PSC.
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Affiliation(s)
- Ming-Hsi Wang
- Mayo Clinic, Mankato, Minnesota, USA
- Mayo Clinic, Rochester, Minnesota, USA
| | | | | | | | | | | | - Kelly Monroe
- Washington University in St Louis, St Louis, Missouri, USA
| | - Billy D Nix
- Washington University in St Louis, St Louis, Missouri, USA
| | | | - William A Faubion
- Mayo Clinic, Rochester, Minnesota, USA
- Mayo Clinic Scottsdale, Scottsdale, Arizona, USA
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Freitas LTDS, Hyppolito EB, Barreto VL, Júnior LHJC, Jorge BCDM, Háteras FCTDSB, Marzola MB, Lima CA, Celedonio RM, Coelho GR, Garcia JHP. Liver transplant in patients with primary sclerosing cholangitis: A retrospective cohort from Northeastern Brazil. World J Hepatol 2023; 15:1033-1042. [PMID: 37900212 PMCID: PMC10600696 DOI: 10.4254/wjh.v15.i9.1033] [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: 05/07/2023] [Revised: 07/07/2023] [Accepted: 08/25/2023] [Indexed: 09/22/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) manifests within a broad ethnic and racial spectrum, reflecting different levels of access to health care. AIM To evaluate the clinical profile, complications and survival rates of patients with PSC undergoing liver transplantation (LTx) at a Brazilian reference center. METHODS All patients diagnosed with PSC before or after LTx were included. The medical records were reviewed for demographic and clinical variables, including outcomes and survival. The level of statistical significance was set at P < 0.05. RESULTS Our cohort represented 1.6% (n = 34) of the 2113 patients receiving liver grafts at our service over the past two decades. Most were male (n = 19; 56%). The average age (40 ± 14 years) was similar for men and women (P = 0.347). The mean follow-up time from diagnosis to LTx was 68 mo. Most patients had the classic form of PSC. Three women had PSC/autoimmune hepatitis overlap syndrome, and one patient had small-duct PSC. Alkaline phosphatase levels at diagnosis and pre-LTx model for end-stage liver disease. scores were significantly higher in males. Inflammatory bowel research (IBD) was investigated by colonoscopy in 26/34 (76%) and was present in most cases (18/26; 69%). IBD was less common in women than in men (44.4% vs. 55.6%) (P = 0.692). Cholangiocarcinoma (CCA) was diagnosed in 2/34 (5.9%) patients by histopathology of the explant (survival: 3 years 6 mo, and 4 years 11 mo). Two patients had complications requiring a second LTx (one after 7 d due to hepatic artery thrombosis and one after 17 d due to primary graft dysfunction). Five patients (14.7%) developed biliary stricture. The overall median post-LTx survival was 66 mo. Most deaths occurred in the first year (infection n = 2, primary liver graft dysfunction n = 3, unknown cause n = 1). The 1-year and 5-year survival rates of this cohort were 82.3% and 70.6%, respectively, matching the mean overall survival rates of LTx patients at our center (87.1% and 69.43%, respectively) (P = 0.83). CONCLUSION Survival after 1 and 5 years was similar to that of other LTx indications. The observed CCA survival rate suggests CCA may be an indication for LTx in selected cases.
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Affiliation(s)
| | - Elodie Bomfim Hyppolito
- Liver Transplant Department, Walter Cantídio Teaching Hospital, Fortaleza 60430270, Ceará, Brazil
- School of Medicine, University of Fortaleza, Fortaleza 60811905, Ceará, Brazil
- Hospital São José, Ceará State Health Department, Fortaleza 60455610, Ceará, Brazil
| | | | | | | | | | | | - Clébia Azevedo Lima
- Liver Transplant Department, Walter Cantídio Teaching Hospital, Fortaleza 60430270, Ceará, Brazil
| | - Raquel Mendes Celedonio
- Liver Transplant Department, Walter Cantídio Teaching Hospital, Fortaleza 60430270, Ceará, Brazil
| | - Gustavo Rêgo Coelho
- Liver Transplant Department, Walter Cantídio Teaching Hospital, Fortaleza 60430270, Ceará, Brazil
- Department of Surgery, Federal University of Ceará, Fortaleza 60430140, Ceará, Brazil
- Surgery Department, São Carlos Hospital, Fortaleza 60130241, Ceará, Brazil
| | - Jose Huygens Parente Garcia
- Liver Transplant Department, Walter Cantídio Teaching Hospital, Fortaleza 60430270, Ceará, Brazil
- Department of Surgery, Federal University of Ceará, Fortaleza 60430140, Ceará, Brazil
- Surgery Department, São Carlos Hospital, Fortaleza 60130241, Ceará, Brazil
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Liu B, Qin Z, Cai Z, Liu Z, Chen YL, Yin X, Yin Y, Peng X, Zhang B. Evaluating the Causal Association between Inflammatory Bowel Disease and Risk of Atherosclerotic Cardiovascular Disease: Univariable and Multivariable Mendelian Randomization Study. Biomedicines 2023; 11:2543. [PMID: 37760983 PMCID: PMC10526051 DOI: 10.3390/biomedicines11092543] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 09/07/2023] [Accepted: 09/11/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Observational studies suggested that inflammatory bowel disease (IBD) (i.e., Crohn's disease [CD] and ulcerative colitis [UC]) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease (CAD) and ischemic stroke. However, it is still unclear whether the observed associations causally exist. Thus, we aim to examine the potential effect of IBD, CD, and UC on the risk of CAD and ischemic stroke, using a two-sample Mendelian randomization (MR) study. METHODS Genetic instruments for IBD, CD, and UC were retrieved from the latest published genome-wide association studies (GWASs) of European ancestry. GWAS summary data for instrument-outcome associations were gathered from four independent resources: CARDIoGRAMplusC4D Consortium, MEGASTROKE consortium, FinnGen, and UK Biobank. The inverse variance weighted (IVW) method and multiple pleiotropy-robust approaches were conducted and, subsequently, combined in a fixed-effect meta-analysis. Moreover, multivariable MR (MVMR) analysis was conducted to adjust for potential influencing instrumental variables. RESULTS The IVW method revealed no causal effect of IBD on the risk of CAD (overall IBD on CAD: OR 1.003, 95%CI 0.982 to 1.025; CD on CAD: OR 0.997, 95%CI 0.978 to 1.016; UC on CAD: OR 0.986, 95%CI 0.963 to 1.010) or the risk of ischemic stroke (overall IBD on ischemic stroke: OR 0.994, 95%CI 0.970 to 1.018; CD on ischemic stroke: OR 0.996, 95%CI 0.979 to 1.014; UC on ischemic stroke: OR 0.999, 95%CI 0.978 to 1.020). The results of the meta-analysis and MVMR remained consistent. CONCLUSION Our MR analysis does not support a causal effect of IBD on CAD and ischemic stroke, and previous results from observational studies might be biased through uncontrolled confoundings (such as IBD-specific medications and detection bias, etc.) that warrant further research.
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Affiliation(s)
- Baike Liu
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Zijian Qin
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhaolun Cai
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Zheran Liu
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Yun-Lin Chen
- Department of Cardiology, The 2nd Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
| | - Xiaonan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Yuan Yin
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
| | - Xingchen Peng
- Department of Biotherapy and National Clinical Research Center for Geriatrics, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Bo Zhang
- Gastric Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China
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Shaw DG, Aguirre-Gamboa R, Vieira MC, Gona S, DiNardi N, Wang A, Dumaine A, Gelderloos-Arends J, Earley ZM, Meckel KR, Ciszewski C, Castillo A, Monroe K, Torres J, Shah SC, Colombel JF, Itzkowitz S, Newberry R, Cohen RD, Rubin DT, Quince C, Cobey S, Jonkers IH, Weber CR, Pekow J, Wilson PC, Barreiro LB, Jabri B. Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis. Nat Med 2023; 29:1520-1529. [PMID: 37322120 PMCID: PMC10287559 DOI: 10.1038/s41591-023-02372-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 04/26/2023] [Indexed: 06/17/2023]
Abstract
Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.
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Affiliation(s)
- Dustin G Shaw
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Raúl Aguirre-Gamboa
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Marcos C Vieira
- Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
| | - Saideep Gona
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Nicholas DiNardi
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anni Wang
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anne Dumaine
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA
| | - Jody Gelderloos-Arends
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Zachary M Earley
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | | | - Cezary Ciszewski
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
| | - Anabella Castillo
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Kelly Monroe
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Division of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
- Division of Gastroenterology, Hospital Luz, Lisboa, Portugal
- Faculty of Medicine, Universidade de Lisboa, Lisboa, Portugal
| | - Shailja C Shah
- Division of Gastroenterology, University of California San Diego, San Diego, CA, USA
- Jennifer Moreno VA San Diego Healthcare System, San Diego, CA, USA
| | - Jean-Frédéric Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven Itzkowitz
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Rodney Newberry
- Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, USA
| | - Russell D Cohen
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - David T Rubin
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Christopher Quince
- Organisms and Ecosystems, Earlham Institute, Norwich, NR4 7UZ, UK
- Warwick Medical School, University of Warwick, Coventry, CV4 7HL, UK
- Gut Microbes and Health, Quadram Institute, Norwich, NR4 7UQ, UK
| | - Sarah Cobey
- Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
| | - Iris H Jonkers
- Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | | | - Joel Pekow
- University of Chicago Inflammatory Bowel Disease Center, Chicago, IL, USA
| | - Patrick C Wilson
- Committee on Immunology, University of Chicago, Chicago, IL, USA
- Department of Medicine, University of Chicago, Chicago, IL, USA
- Section of Rheumatology, University of Chicago, Chicago, IL, USA
| | - Luis B Barreiro
- Committee on Immunology, University of Chicago, Chicago, IL, USA.
- Department of Medicine, University of Chicago, Chicago, IL, USA.
- Committee on Genetics, Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.
| | - Bana Jabri
- Committee on Immunology, University of Chicago, Chicago, IL, USA.
- Department of Medicine, University of Chicago, Chicago, IL, USA.
- Department of Pathology, University of Chicago, Chicago, IL, USA.
- Department of Pediatrics, University of Chicago, Chicago, IL, USA.
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Yablokova EA, Dzhabarova AK, Lokhmatov MM, Gorelov AV, Krutikhina SB, Erokhina MI, Chibrina EV, Rimskaya AM, Khavkin AI. Extraintestinal manifestations in infl ammatory bowel diseases in children, a modern view of the problem. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2023; 1:165-177. [DOI: 10.31146/1682-8658-ecg-209-1-165-177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Inflammatory bowel disease (IBD) is a group of severe systemic diseases with a multiple intestinal and extraintestinal manifestations (EIM). EIM can affect any organ systems, determine the course, therapy and prognosis of the underlying disease. The frequency of EIM (6–80%) differs significantly in studies depending on the cohort of patients (number, age of patients, IBD phenotype). In 6–10% of children EIM are the first symptoms of the disease. The classification of EIM most often depends on the activity of the disease in the intestine. The most commonly affected «target organs» in children and adults are joints, skin and mucous membranes, eyes, and the hepatobiliary system. Physical development delay is specific for children IBD, not always reversible. The article highlights the incidence of ulcerative colitis and Crohn’s disease EIM in children and adults, analyzes the basics of epidemiology, pathogenesis, clinical manifestations, approaches to the diagnosis and treatment of arthritis, growth disorders, mucocutaneous, ocular and hepatobiliary EIM of IBD in children. Therapy of EIM associated with IBD activity is aimed at controlling the underlying disease and includes a wide range of drugs, ФНОα antagonists are the most effective. The treatment protocols for other EIM are not standardized in either adult or pediatric practice and are significantly less successful.
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Affiliation(s)
- E. A. Yablokova
- Research Clinical Institute of Childhood of the Moscow Region;
First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | | | - M. M. Lokhmatov
- First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - A. V. Gorelov
- First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University);
Federal budget institute of science “Central research institute of epidemiology” of the Federal Service on Surveillance for consumer rights protection and human well-being
| | - S. B. Krutikhina
- First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - M. I. Erokhina
- Research Clinical Institute of Childhood of the Moscow Region
| | - E. V. Chibrina
- Research Clinical Institute of Childhood of the Moscow Region
| | - A. M. Rimskaya
- First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)
| | - A. I. Khavkin
- Research Clinical Institute of Childhood of the Moscow Region;
Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery of the Pirogov Russian National Research Medical University Research Clinical Institute of Pediatrics;
Belgorod National Research University
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7
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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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8
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Reutemann B, Gordon FD. Evaluation of the Patient with Markedly Abnormal Liver Enzymes. Clin Liver Dis 2023; 27:1-16. [PMID: 36400459 DOI: 10.1016/j.cld.2022.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Liver enzyme tests are very commonly ordered by physicians, and when they return as abnormal, they can pose a clinical challenge to the provider. Markedly abnormal liver enzymes indicate severe hepatic injury and require immediate evaluation. There are various causes for abnormal liver tests, including infectious, autoimmune, genetic, metabolic, drug, and vascular causes. An understanding of the patterns of aminotransferase and alkaline phosphatase elevations is useful in narrowing the differential diagnosis. A thorough history and physical examination, appropriate blood testing, and imaging are typically key to evaluating the patient with abnormal liver enzymes.
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Affiliation(s)
- Bethany Reutemann
- Dartmouth Hitchock Medical Center, 100 Hitchcock Way, Manchester, NH 03104, USA.
| | - Fredric D Gordon
- Tufts Medical Center, 800 Washington St. #40, South Building, 4th floor, Boston, MA 02111, USA
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9
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Nguyen A, Sagvand BT, Alizadeh M, Nguyen C, Scott W, von Rosenvinge EC. Primary sclerosing cholangitis and pancreatic cancer: A retrospective cohort study of United States veterans. FRONTIERS IN GASTROENTEROLOGY (LAUSANNE, SWITZERLAND) 2023; 1:1076788. [PMID: 38347877 PMCID: PMC10860374 DOI: 10.3389/fgstr.2022.1076788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
Primary sclerosing cholangitis (PSC) is associated with hepatobiliary and colorectal cancers, but it remains uncertain if PSC increases the risk for pancreatic cancer. While some European studies have suggested an increased risk of pancreatic cancer in PSC patients, other studies have not. And these studies did not well account for presence or absence of concomitant inflammatory bowel disease (IBD). The purpose of this study is to investigate the prevalence of pancreatic cancer in United States veterans with PSC both with and without IBD. Methods This retrospective study used International Classification of Diseases, Tenth Revision (ICD-10) codes to identify patients with PSC, IBD, and pancreatic cancer from the Veterans Affairs (VA) Corporate Data Warehouse. The prevalence of pancreatic cancer in patients with PSC only, IBD only, PSC with IBD, and neither PSC nor IBD were compared. Logistic regression was used to control for age, gender, chronic pancreatitis, diabetes mellitus, and tobacco and alcohol use. Results A total of 946 patients with PSC were identified from a population of over 9 million veterans. 486 (51.4%) of these had concurrent IBD. Additionally 112,653 patients with IBD without PSC were identified. When adjusted for confounding factors, patients with PSC had a significantly higher prevalence of pancreatic cancer compared to the general population and those with IBD without PSC (2.4% vs. 0.2% and 0.5%, respectively). Conclusions Veterans with PSC, particularly those without concomitant IBD, have a high prevalence of pancreatic cancer compared to the general veteran population. Our findings support the need for multicenter prospective studies investigating the benefits of screening for pancreatic cancer in patients with PSC.
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Affiliation(s)
- Anita Nguyen
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, United States
| | - Babak Torabi Sagvand
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland Medical Center, Baltimore, MD, United States
| | - Madeline Alizadeh
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
- Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Cydney Nguyen
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
- Department of Medicine, University of Maryland Medical Center, Baltimore, MD, United States
| | - William Scott
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
| | - Erik C. von Rosenvinge
- Department of Veterans Affairs, Veterans Affairs (VA) Maryland Health Care System, Baltimore, MD, United States
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland Medical Center, Baltimore, MD, United States
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Attauabi M, Wewer MD, Bendtsen F, Seidelin JB, Burisch J. Inflammatory Bowel Diseases Affect the Phenotype and Disease Course of Coexisting Immune-Mediated Inflammatory Diseases: A Systematic Review With Meta-Analysis. Inflamm Bowel Dis 2022; 28:1756-1765. [PMID: 35134921 DOI: 10.1093/ibd/izac003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND It is unclear whether inflammatory bowel diseases (IBDs) affect the phenotype and severity of co-occurring immune-mediated inflammatory diseases (IMIDs). We aimed to investigate the characteristics of IMIDs in relation to co-occurring IBD. METHODS We conducted a systematic review of Medline and EMBASE databases from inception to September 2020. We identified studies reporting the phenotype, severity, or disease course of IMIDs among patients with or without co-occurring IBD. A meta-analysis was conducted using random effects models. RESULTS The electronic search yielded 13 220 studies that we narrowed down to 73 eligible studies for full-text review, including 42 on primary sclerosing cholangitis, 12 on axial spondyloarthropathies, and 8 studies on psoriasis. In primary sclerosing cholangitis, IBD was associated with less frequent involvement of extrahepatic bile ducts (risk ratio [RR], 0.50; 95% confidence interval [CI], 0.33-0.75), longer liver transplantation-free survival (hazard ratio, 0.70; 95% CI, 0.60-0.82), and no increased risk of cholangiocarcinoma (RR, 0.88; 95% CI, 0.59-1.31). Patients with axial spondyloarthropathies and co-occurring IBD were characterized by an increased risk of dactylitis (RR, 2.06; 95% CI, 1.24-3.42), a lower Bath Ankylosing Spondylitis Radiology Index (mean difference [MD] = -2.28; 95% CI, -3.26 to -1.30), and better Schober's test results (MD = 1.07; 95% CI, 0.64-1.49). Psoriasis and co-occurring IBD was associated with reduced disease severity (RR, 1.41; 95% CI, 1.02-1.96) and less frequent presentation in nails (RR, 0.14; 95% CI, 0.05-0.42), with no apparent impact on psoriatic arthritis (RR, 0.94; 95% CI, 0.27-3.31). CONCLUSIONS This systematic review with meta-analysis found IBD is associated with a distinct disease phenotype among the IMIDs investigated. Our findings emphasize the importance of multidisciplinary approaches to patients with co-occurring IMIDs and IBD.
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Affiliation(s)
- Mohamed Attauabi
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Mads Damsgaard Wewer
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
| | - Jakob Benedict Seidelin
- Department of Gastroenterology and Hepatology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Gastrounit, Medical Section, Hvidovre Hospital, Hvidovre, Denmark
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11
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Stevens JP, Gupta NA. Recent Insights into Pediatric Primary Sclerosing Cholangitis. Clin Liver Dis 2022; 26:489-519. [PMID: 35868687 DOI: 10.1016/j.cld.2022.03.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
This article reviews recent literature on the pathogenesis, presentation, diagnosis, comorbidities, natural history, and management of pediatric primary sclerosing cholangitis (PSC). The authors shed light on the role of genetic and environmental factors in PSC, although recognize the limitations in the understanding of PSC pathogenesis. They reflect on presenting disease phenotypes, including the association with inflammatory bowel disease and frequent histologic presence of autoimmune hepatitis features. The current lack of effective medications is discussed, and disease complications and prognosis are described. Finally, the authors highlight available evidence while acknowledging the paucity of prospective pediatric data.
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Affiliation(s)
- James P Stevens
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, 1760 Haygood Drive, Atlanta GA 30322, USA
| | - Nitika A Gupta
- Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, 1760 Haygood Drive, Atlanta GA 30322, USA.
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12
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UGAR M, KAMIŞ F, BEYAZIT Y. İnflamatuvar barsak hastalığı olan hastalarda klinik özellikler, tedavi seçenekleri ve komplikasyonların değerlendirilmesi. FAMILY PRACTICE AND PALLIATIVE CARE 2022. [DOI: 10.22391/fppc.1088562] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Introduction: Inflammatory bowel diseases (IBD) form a group of inflammatory diseases occurring in genetically-susceptible people, which are characterized by chronic progression and whose cause is not fully known. The aim of this study is to determine the incidence of IBD in our region and examine the clinical characteristics, sociodemographic features, and treatment results of IBD patients.Methods: Our study retrospectively investigates 211 patients over 18 years of age who were monitored for an IBD diagnosis between January 2, 2013, and December 31, 2019, by the gastroenterology department of Canakkale Onsekiz Mart University’s Faculty of Medicine. The mean age, female-male ratio, smoking habits, disease severity, and localization sites were identified for included patients. Local and systemic complications of administered treatment types and reasons for surgical treatment were also assessed in patients.Results: Of the 211 patients with IBD diagnoses, 158 (74.9%) had Ulcerative Colitis (UC) and 53 (25.1%) had a diagnosis of Crohn’s disease (CD). The mean age at the time of diagnosis was 43.97±16.22 years for UC patients and 42.30±14.73 years for CD cases. The involvement sites for UC were distal colitis for 58.4% of patients, left colon for 24.1% of patients, pancolitis for 16.5% of patients, and backwash ileitis for 7% of patients. According to the treatment results, 152 (72.0%) patients took 5-aminosalicylate (5-ASA) alone, 48 (22.8%) took thiopurine, and 20 (9.5%) took anti-TNF.Conclusion: Knowing the demographic, clinical, and laboratory features of these diseases, which are frequently seen in our region, can support the early identification of probable complications that may occur and the selection of appropriate approaches during diagnosis, treatment, and follow-up monitoring of these diseases.Keywords: Inflammatory Bowel Diseases, Ulcerative Colitis, Crohn’s Disease, Severity of Illness Index, Abdominal Pain, Diarrhea
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Affiliation(s)
- Mücahit UGAR
- Department of Internal Medicine, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
| | - Fatih KAMIŞ
- Department of Internal Medicine, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
| | - Yavuz BEYAZIT
- Department of Gastroenterology, Faculty of Medicine, Canakkale Onsekiz Mart University, Canakkale
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Vessby J, Wisniewski JR, Lindskog C, Eriksson N, Gabrysch K, Zettl K, Wanders A, Carlson M, Rorsman F, Åberg M. AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2022; 13:e00486. [PMID: 35363634 PMCID: PMC9132532 DOI: 10.14309/ctg.0000000000000486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 03/15/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue. METHODS Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry. RESULTS In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC. DISCUSSION We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance.
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Affiliation(s)
- Johan Vessby
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Jacek R. Wisniewski
- Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany;
| | - Cecilia Lindskog
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;
| | - Niclas Eriksson
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden;
| | - Katja Gabrysch
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden;
| | - Katharina Zettl
- Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany;
| | - Alkwin Wanders
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark;
| | - Marie Carlson
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Fredrik Rorsman
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Mikael Åberg
- Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Possible role of the HMGB1 and RAGE inflammatory pathway in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol 2022; 46:101791. [PMID: 34400366 DOI: 10.1016/j.clinre.2021.101791] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Accepted: 07/28/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND Activation of the receptor for advanced glycation end products (RAGE) and its ligand High Mobility Group Box Protein 1 (HMGB1), a nuclear protein with proinflammatory properties, has been implicated in several inflammatory disorders. OBJECTIVE To analyse the influence of RAGE and HMGB1 signalling in patients with primary sclerosing cholangitis (PSC). METHODS Levels of HMGB1 and bile acid in serum and bile samples of 69 PSC patients and 32 controls were measured. Additionally, 640 patients with PSC and other liver diseases were analysed for the gain-of-function RAGE G82S SNP by PCR. Laboratory and clinical parameters were retrieved by chart review. RESULTS ELISA analysis showed significantly higher biliary HMGB1 concentrations in PSC patients (n=69, median 124,1 ng/ml) than in the control group (n=32, median 6,85 ng/ml, p<0,001). Median serum HMGB1 (n=22, median 2,4 ng/ml) was significantly lower than median biliary HMGB1 of the concomitant bile samples (n=22, median 151 ng/ml, p =0,001). There was no correlation of biliary HMGB1 levels with laboratory parameters or clinical end points. Analysis of the gain-of-function G82SSNP RAGE SNP in PSC patients showed 8 patients with heterozygote mutant alleles (8/324, 2,5%). Patients carrying the mutation developed more often dominant strictures of the large bile ducts (100.0% vs. 61.3%; p=0.04) and had reduced transplantation-free survival in the mutant allele group (p<0.001). CONCLUSIONS Biliary HMGB1 levels are elevated in PSC patients compared to controls and a gain-of-function SNP in RAGE is associated with development of dominant strictures and reduced survival in PSC patients.
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15
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Makharia G, Mohta S, Sridharan S, Gopalakrishnan R, Prasad N, Bansal S. Diarrhea in solid organ transplant recipients in the South Asian Region - Expert group opinion for diagnosis and management. INDIAN JOURNAL OF TRANSPLANTATION 2022; 16:23. [DOI: 10.4103/ijot.ijot_79_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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16
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Alborzi F, Ebrahimi Daryani N, Deihim T, Azizi Z, Azmoudeh Ardalan F, Teimouri A, Taslimi R, Roshan N, Mami M, Mirzade M, Aletaha N. Colonic Mucosal Infiltration of IgG4 Plasma Cells and Ulcerative Colitis: Determinant of Presence, Activity, Extension, and Duration of Disease. Middle East J Dig Dis 2021; 13:287-293. [PMID: 36606008 PMCID: PMC9489443 DOI: 10.34172/mejdd.2021.237] [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: 01/21/2021] [Accepted: 06/11/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Infiltration of IgG4 positive plasma cells has been detected in the colonic mucosa of patients with ulcerative colitis (UC). The aim of the study was to investigate the association between colonic mucosal infiltration of IgG4 plasma cells and the presence, activity, extension, and duration of UC. METHODS In this case-control study (2009-2014), 102 subjects (84 with UC/18 controls) were enrolled. Clinical records and rectosigmoid biopsies of UC patients were selected, and biopsies were stained with IgG4 monoclonal antibodies. IgG4 positive plasma cells were counted by a single pathologist. RESULTS Amongst 84 patients with UC, 73.8% had UC without primary sclerosing cholangitis (PSC), and 26.2% had UC with PSC. IgG4 plasma cells were seen in 35 (41.7%) patients with UC and 0% of controls (p = 0.001). The mean amount of IgG4 containing plasma cells was significantly different between active and inactive patients with UC, although it was not significantly different between UC patients with and without PSC. The presence of IgG4 infiltration was significantly associated with the extension and duration of the disease. Furthermore, IgG4 count had a sensitivity/specificity of 78.6%/83.3% for the diagnosis of UC. CONCLUSION Our study revealed the diagnostic role of IgG4 plasma cells in the colonic mucosa of patients with UC and its association with activity, extension, and duration of disease.
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Affiliation(s)
- Foroogh Alborzi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasser Ebrahimi Daryani
- Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Tina Deihim
- Internal Medicine Resident, Internal Medicine Department, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Azizi
- Researcher, Iran University of Medical Sciences, Tehran, Iran
| | | | - Azam Teimouri
- Assistant Professor of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Reza Taslimi
- Assistant Professor of Gastroenterology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
| | - Nader Roshan
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
| | - Masood Mami
- Assistant Professor of Gastroenterology, Ilam University of Medical Sciences, Ilam, Iran
| | - Monirsadat Mirzade
- Resident of Community Medicine, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Najmeh Aletaha
- Associate Professor of Gastroenterology, Tehran University of Medical Sciences, Tehran, Iran
,Corresponding Author: Najmeh Aletaha,MD Gastroentrology and Hepatology Ward, Imam Khomeini Hospital, Tehran university of Medical Science, Tehran, Iran Tel: + 98 21 88799446 Fax: + 98 21 88799840
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Tse CS, Deepak P, Papadakis K. Inflammatory Bowel Disease, Celiac Disease, and Primary Sclerosing Cholangitis: Is There a Link? Gastroenterology 2021; 160:2207. [PMID: 33385427 DOI: 10.1053/j.gastro.2020.07.068] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Accepted: 07/19/2020] [Indexed: 12/02/2022]
Affiliation(s)
- Chung Sang Tse
- Division of Gastroenterology, Brown University, Warren Alpert Medical School, Providence, RI
| | - Parakkal Deepak
- Division of Gastroenterology, Washington University in St Louis School of Medicine, St Louis, MO
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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: 30] [Impact Index Per Article: 7.5] [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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19
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Kim JM, Cheon JH. Pathogenesis and clinical perspectives of extraintestinal manifestations in inflammatory bowel diseases. Intest Res 2020; 18:249-264. [PMID: 32295331 PMCID: PMC7385581 DOI: 10.5217/ir.2019.00128] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 11/25/2019] [Accepted: 03/06/2020] [Indexed: 12/13/2022] Open
Abstract
A considerable number of patients with inflammatory bowel disease (IBD) experience extraintestinal manifestations (EIMs), which can present either before or after IBD diagnosis. Unraveling the pathogenic pathways of EIMs in IBD is challenging because of the lack of reliable criteria for diagnosis and difficulty in distinguishing EIMs from external pathologies caused by drugs or other etiologies. Optimizing treatment can also be difficult. Early diagnosis and management of EIM revolve around multidisciplinary teams, and they should have the resources necessary to make and implement appropriate decisions. In addition, specialists of the affected organs should be trained in IBD treatment. Furthermore, patient awareness regarding the extraintestinal symptoms of IBD is of paramount importance for improving patient understanding of disease and health outcomes. Herein, we review the pathogenesis and clinical perspectives of EIMs in IBD.
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Affiliation(s)
- Jung Min Kim
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Hee Cheon
- Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Avison Biomedical Research Center, Severance Hospital, Seoul, Korea
- Affiliate Faculty, Pohang University of Science and Technology (POSTECH), Pohang, Korea
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20
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Wang MH, Mousa OY, Friton JJ, Raffals LE, Leighton JA, Pasha SF, Picco MF, Cushing KC, Monroe K, Nix BD, Newberry RD, Faubion WA. Unique Phenotypic Characteristics and Clinical Course in Patients With Ulcerative Colitis and Primary Sclerosing Cholangitis: A Multicenter US Experience. Inflamm Bowel Dis 2020; 26:774-779. [PMID: 31626701 PMCID: PMC7534392 DOI: 10.1093/ibd/izz209] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC) is a rare phenotype. We aimed to assess patients with UC-PSC or UC alone and describe differences in clinical and phenotypic characteristics, antitumor necrosis factor (TNF) therapy, and long-term clinical outcomes. METHODS This retrospective multicenter cohort study included patients who received a diagnosis of UC from 1962 through 2015. We evaluated clinical factors associated with UC-PSC vs UC alone and assessed associations by using multivariable logistic regression models. RESULTS Among 522 patients with UC, 56 (10.7%) had PSC. Compared with UC alone, patients with UC-PSC were younger (younger than 20 years) at diagnosis (odds ratios [OR], 2.35; adjusted P = 0.02) and had milder UC severity (adjusted P = 0.05), despite having pancolonic involvement (OR, 7.01; adjusted P < 0.001). In the biologics era (calendar year 2005 to 2015), patients with UC-PSC less commonly received anti-TNF therapy compared with patients with UC (OR, 0.38; adjusted P = 0.009), but their response rates were similar. Fewer patients with UC-PSC received corticosteroids (OR, 0.24; adjusted P = 0.005) or rectal 5-aminosalicyte acid (OR, 0.26; adjusted P < 0.001). Other differences were identified that were not statistically significant in a multivariable model: patients with UC-PSC more commonly were male, had lower rates of smoking, and had higher rates of colorectal cancer and colectomy. DISCUSSION This study identified a unique phenotype of UC with concurrent PSC, which had different clinical behavior compared with UC only. These phenotypic characteristics can help identify high-risk patients with UC before PSC is diagnosed and guide different management and monitoring strategies.
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Affiliation(s)
- Ming-Hsi Wang
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
- Gastroenterology, Mayo Clinic Health System in Mankato, Mankato, Minnesota, USA
| | - Omar Y Mousa
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jessica J Friton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Laura E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Jonathan A Leighton
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Shabana F Pasha
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Michael F Picco
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida, USA
| | - Kelly C Cushing
- Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Kelly Monroe
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Billy D Nix
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Rodney D Newberry
- Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri, USA
| | - William A Faubion
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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Guerra I, Bujanda L, Castro J, Merino O, Tosca J, Camps B, Gutiérrez A, Gordillo Ábalos J, de Castro L, Iborra M, Carbajo AY, Taxonera C, Rodríguez-Lago I, Mesonero F, de Francisco R, Gómez-Gómez GJ, Chaparro M, Tardillo CA, Rivero M, Algaba A, Martín Arranz E, Cañete F, Vicente R, Sicilia B, Antolín B, Prieto V, Márquez L, Benítez JM, Camo P, Piqueras M, Gargallo CJ, Hinojosa E, Huguet JM, Pérez Calle JL, Van Domselaar M, Rodriguez C, Calvet X, Muñoz-Villafranca C, García-Sepulcre MF, Munoz-Garrido P, Fernández-Clotet A, Gómez Irwin L, Hernández S, Guardiola J, Sempere L, González Muñoza C, Hernández V, Beltrán B, Barrio J, Alba C, Moraleja I, López-Sanromán A, Riestra S, Martínez Montiel P, Garre A, Arranz L, García MJ, Martín Arranz MD, Corsino P, Arias L, Fernández-Salazar L, Fernández-Pordomingo A, Andreu M, Iglesias E, Ber Y, Mena R, Arroyo Villarino MT, Mora M, Ruiz L, López-Serrano P, Blazquez I, Villoria A, Fernández M, Bermejo F, Banales JM, Domènech E, Gisbert JP. Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study. J Crohns Colitis 2019; 13:1492-1500. [PMID: 31063540 DOI: 10.1093/ecco-jcc/jjz094] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. METHODS PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. RESULTS In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. CONCLUSIONS PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.
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Affiliation(s)
- Ivan Guerra
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Luis Bujanda
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | | | - Olga Merino
- Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain
| | - Joan Tosca
- Hospital Universitario Clínico de Valencia, Department of Medicine, University of Valencia, Valencia, Spain
| | - Blau Camps
- Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), l'Hospitalet de Llobregat, Spain
| | - Ana Gutiérrez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | - Luisa de Castro
- Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica. Estructura Organizativa de Xestión Integrada de Vigo, Vigo, Spain
| | - Marisa Iborra
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | | | - Carlos Taxonera
- Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | | | | | - Ruth de Francisco
- Hospital Universitario Central De Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Carlos A Tardillo
- Hospital Universitario Nuestra Señora Candelaria, Santa Cruz De Tenerife, Spain
| | - Montserrat Rivero
- Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain
| | - Alicia Algaba
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Eduardo Martín Arranz
- Hospital Universitario La Paz and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid
| | - Fiorella Cañete
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | | | | | - Beatriz Antolín
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | | | - José M Benítez
- Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | | | - Carla J Gargallo
- Hospital Clínico Universitario "Lozano Blesa" and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | | | - José M Huguet
- Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Manuel Van Domselaar
- Hospital Universitario de Torrejón and Universidad Francisco de Vitoria, Madrid, Spain
| | | | - Xavier Calvet
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Corporació Sanitària Universitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain
| | | | | | - Patricia Munoz-Garrido
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | | | | | - Sherly Hernández
- Hospital Universitario Clínico de Valencia, Department of Medicine, University of Valencia, Valencia, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), l'Hospitalet de Llobregat, Spain
- Universitat de Barcelona, Spain
| | - Laura Sempere
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | - Vicent Hernández
- Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica. Estructura Organizativa de Xestión Integrada de Vigo, Vigo, Spain
| | - Belén Beltrán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | | | - Cristina Alba
- Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | | | | | - Sabino Riestra
- Hospital Universitario Central De Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | - Ana Garre
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Laura Arranz
- Hospital Universitario Nuestra Señora Candelaria, Santa Cruz De Tenerife, Spain
| | - María José García
- Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain
| | - María Dolores Martín Arranz
- Hospital Universitario La Paz and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid
| | - Pilar Corsino
- Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Lara Arias
- Hospital Universitario de Burgos, Burgos, Spain
| | | | | | | | - Eva Iglesias
- Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | | | | | | | - Lucía Ruiz
- Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Isabel Blazquez
- Hospital Universitario de Torrejón and Universidad Francisco de Vitoria, Madrid, Spain
| | - Albert Villoria
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Complejo hospitalario de Navarra, Pamplona, Spain
| | - María Fernández
- Corporació Sanitària Universitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain
| | - Fernando Bermejo
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Jesus M Banales
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Ikerbasque (Basque Foundation for Sciencies), Bilbao, Spain
| | - Eugeni Domènech
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
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Vessby J, Lampinen M, Åberg M, Rorsman F, Siegbahn A, Wanders A, Carlson M. Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis. Ups J Med Sci 2019; 124:238-245. [PMID: 31774347 PMCID: PMC6968534 DOI: 10.1080/03009734.2019.1689209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Background: Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal cancer prognostication. Here we evaluate TF expression in an inflammatory bowel disease (IBD) cohort, with special focus on differences between UC and PSC-UC patients.Materials and methods: Colonic biopsies from UC (n = 23), PSC (n = 24), and healthy controls (n = 11) were stained for TF by immunohistochemistry. Mononuclear cell contribution to TF expression was verified using flow cytometry.Results: TF was distributed at three distinct colonic locations: in subepithelial pericryptal sheath cells, in mononuclear cells, and in the intestinal stroma. In contrast to UC-where inflammation was accompanied with TF up-regulation-PSC-UC activity remained low during inflammation. Stromal TF positivity was found exclusively in ongoing inflammation.Conclusion: Our study provides additional support for a divergent pathogenesis in PSC-UC, with an inflammatory environment that differs from classical UC. Stromal TF emerges as a new marker of colonic inflammation.
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Affiliation(s)
- Johan Vessby
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Maria Lampinen
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Mikael Åberg
- Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Fredrik Rorsman
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Agneta Siegbahn
- Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Alkwin Wanders
- Department of Medical Biosciences, Umeå University, Umeå, Sweden
| | - Marie Carlson
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
- CONTACT Marie Carlson Gastroenterology Research Group, Department of Medical Sciences, University Hospital Akademiska, S-751 85 Uppsala, Sweden
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23
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Sundaram S, Jearth V. Primary Sclerosing Cholangitis: A Clinical Update. EUROPEAN MEDICAL JOURNAL 2019. [DOI: 10.33590/emj/10313809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic disorder of the liver, with strictures in the bile ducts leading to cirrhosis of the liver in a proportion of patients. PSC is commonly associated with inflammatory bowel disease and increased risk of cholangiocarcinoma, gall bladder cancer, colorectal cancer, and hepatocellular carcinoma. Medical therapies are primarily aimed at symptom management and disease-modifying therapies are limited. Endoscopic therapies are used in patients with dominant strictures and liver transplantation is a last resort. In this article, the authors aim to comprehensively review the epidemiology, diagnosis, and management of PSC with emphasis on risk of malignancies and management of PSC. The authors also survey the advances in pathogenesis understanding and novel medical therapies for PSC.
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Affiliation(s)
- Sridhar Sundaram
- Department of Gastroenterology, Seth GS Medical College and KEM Hospital, Mumbai, India
| | - Vaneet Jearth
- Department of Digestive Diseases and Clinical Nutrition, Tata Memorial Centre, Mumbai, India
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24
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Zipprich A. Rheumatologie und Hepatologie: Diagnostik und Therapie von
autoimmunen Lebererkrankungen. AKTUEL RHEUMATOL 2019. [DOI: 10.1055/a-0885-9314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
ZusammenfassungUnter autoimmunen Lebererkrankungen werden im klassischen Sinne 3 verschiedene
Entitäten, die Autoimmune Hepatitis (AIH), die Primär biliäre Cholangitis (PBC)
und die Primär sklerosierende Cholangitis (PSC) verstanden. Der nachfolgende
Übersichtartikel fokusiert auf die Diagnostik und die Therapie dieser 3
autoimmunen Lebererkrankungen und gibt eine Übersicht zu möglichen zusätzlich
assoziierten Autoimmunerkrankungen.
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25
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Annese V. A Review of Extraintestinal Manifestations and Complications of Inflammatory Bowel Disease. SAUDI JOURNAL OF MEDICINE & MEDICAL SCIENCES 2019; 7:66-73. [PMID: 31080385 PMCID: PMC6503692 DOI: 10.4103/sjmms.sjmms_81_18] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Extraintestinal manifestations (EIMs) are common in inflammatory bowel disease (IBD), in both Crohn's disease and ulcerative colitis. Almost any organ system can be affected, including the musculoskeletal, dermatologic, renal, hepatopancreatobiliary, pulmonary and ocular systems. However, the musculoskeletal and dermatologic systems are the most commonly involved sites of manifestations. While some manifestations such as peripheral arthritis and erythema nodosum have an association with IBD activity, others such as axial arthropathy, pyoderma gangrenosum and primary sclerosing cholangitis have an independent disease course. This review provides a summary of the most common EIMs in IBD and their prevalence and management.
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Affiliation(s)
- Vito Annese
- Department of Gastroenterology, Valiant Clinic, Dubai, United Arab Emirates
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26
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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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27
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Lampinen M, Vessby J, Fredricsson A, Wanders A, Rorsman F, Carlson M. High Serum sCD40 and a Distinct Colonic T Cell Profile in Ulcerative Colitis Associated With Primary Sclerosing Cholangitis. J Crohns Colitis 2019; 13:341-350. [PMID: 30383225 DOI: 10.1093/ecco-jcc/jjy170] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS There is a strong association between primary sclerosing cholangitis [PSC] and ulcerative colitis [UC], but the immunological link between the two diseases is obscure. We compared serum cytokine profiles of patients with PSC-UC and UC, and investigated a number of selected cytokines in colonic biopsy samples. We also assessed the presence and activation of T cells in peripheral blood and colonic mucosa. METHODS Serum samples from 22 patients with PSC-UC, 28 patients with UC, and 19 controls were analysed by a proximity extension assay including 92 inflammatory cytokines. Biopsies from caecum, sigmoid colon, and rectum were collected from the same patients. Quantitative analysis for IFN-γ, IL-2, IL-4, IL-5, IL-13, IL-17A/ E/F, IL-21, IL-22, IL-23, and IL-27 was carried out on tissue homogenates. T cell phenotype was evaluated by flow cytometry. RESULTS By multivariate analysis we identified a cluster of serum cytokines with higher levels in PSC-UC, and sCD40 in particular was strongly associated with this patient group. In contrast, colonic cytokines were only modestly increased in PSC-UC, whereas several Th1-, Th2-, and Th17-associated cytokines were increased in UC. Patients with PSC-UC had increased colonic levels of CXCR3-positive CD8+ T cells but fewer CD25-positive CD4+ T cells. An increased CRTH2/CXCR3-quote indicated a predominance of Th-2 type CD4+ T cells in UC patients. CONCLUSIONS Our study reveals different cytokine profiles and T cell profiles in PSC-UC and UC, with higher systemic levels of cytokines in PSC-UC, and a more pronounced colonic inflammation in UC. Serum sCD40 could potentially be investigated as a marker for PSC in UC.
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Affiliation(s)
- Maria Lampinen
- Department of Medical Sciences, Gastroenterology Research Group, University Hospital, Uppsala, Sweden
| | - Johan Vessby
- Department of Medical Sciences, Gastroenterology Research Group, University Hospital, Uppsala, Sweden
| | - Annika Fredricsson
- 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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28
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Te HS. Laboratory Measurement of Hepatic Function. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT, 2 VOLUME SET 2019:1398-1409. [DOI: 10.1016/b978-0-323-40232-3.00119-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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29
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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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30
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Tse CS, Loftus EV, Raffals LE, Gossard AA, Lightner AL. Effects of vedolizumab, adalimumab and infliximab on biliary inflammation in individuals with primary sclerosing cholangitis and inflammatory bowel disease. Aliment Pharmacol Ther 2018; 48:190-195. [PMID: 29808485 DOI: 10.1111/apt.14829] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 03/28/2018] [Accepted: 05/08/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017. Hepatic biochemistries were compared using the paired t-test (patients served as their own controls) ≤3 months before and 6-8 and 12-14 months after biological initiation. Radiographic information of biliary stenosis and liver fibrosis were obtained via abdominal ultrasound, abdominal magnetic resonance imaging and magnetic resonance elastography. RESULTS Use of adalimumab was associated with a significant decrease in alkaline phosphatase (ALP) after 6-8 months (P = 0.03; mean change -70 U/L, standard deviation [SD] 88 U/L) compared to vedolizumab (mean change +50 U/L, SD 142 U/L) or infliximab (mean change +37 U/L, SD 183 U/L) but the change was not significant after 12-14 months (P = 0.24). No significant decreases were observed with AST, ALT, total or direct bilirubin, elastography score or radiographic imaging of biliary tree dilation/strictures with any biological therapy after 6-8 or 12-14 months. CONCLUSIONS Current evidence suggests that biological therapies used for the treatment of IBD are not effective treatments for PSC. Further study is needed to elucidate any potential beneficial effect of adalimumab on PSC.
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Affiliation(s)
- C S Tse
- Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA
| | - E V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - L E Raffals
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - A A Gossard
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA
| | - A L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
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31
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Tumor Necrosis Factor Alpha Inhibition for Inflammatory Bowel Disease after Liver Transplant for Primary Sclerosing Cholangitis. Case Rep Gastrointest Med 2018; 2018:1015408. [PMID: 29862092 PMCID: PMC5976998 DOI: 10.1155/2018/1015408] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 04/15/2018] [Indexed: 11/17/2022] Open
Abstract
Background Outcome data regarding the use of tumor necrosis factor alpha inhibitors (anti-TNFα) in patients with inflammatory bowel disease (IBD) after liver transplant (LT) for primary sclerosing cholangitis (PSC) are scant. Methods We performed a retrospective chart review to investigate outcomes among a series of post-liver-transplant PSC/IBD patients receiving anti-TNFα therapy at Henry Ford Health System ((HFHS), Detroit, MI). Results A total of five patients were treated with anti-TNFα agents for IBD after LT for PSC from 1993 through 2015. Two patients were treated with adalimumab, and three were treated with infliximab. Three patients were hospitalized with severe posttransplant infections. Two patients developed posttransplant lymphoproliferative disease (PTLD); one of these patients died due to complications of PTLD. Conclusion Anti-TNFα treatment following LT worsened the disease course in our patients with concurrent PSC/IBD and led to serious complications and surgical intervention. Larger studies are needed to evaluate the side effects and outcomes of the use of such agents in this patient population. Until then, clinicians should have a high threshold to use anti-TNFα therapy in this setting.
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Waldum HL, Björnsson ES, Brenna E. Chronic cholestatic liver diseases. Scand J Gastroenterol 2018; 52:788. [PMID: 28276829 DOI: 10.1080/00365521.2017.1296276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Helge L Waldum
- a St. Olavs Hospital , Norwegian University of Science and Technology , Trondheim , Norway
| | - Einar S Björnsson
- b Landspitali - The National University Hospital of Iceland , Reykjavik , Iceland
| | - Eiliv Brenna
- a St. Olavs Hospital , Norwegian University of Science and Technology , Trondheim , Norway
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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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Lindström L, Jørgensen KK, Boberg KM, Castedal M, Rasmussen A, Rostved AA, Isoniemi H, Bottai M, Bergquist A. Risk factors and prognosis for recurrent primary sclerosing cholangitis after liver transplantation: a Nordic Multicentre Study. Scand J Gastroenterol 2018; 53:297-304. [PMID: 29301479 DOI: 10.1080/00365521.2017.1421705] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The risk for recurrent primary sclerosing cholangitis (rPSC) after liver transplantation is associated with inflammatory bowel disease (IBD). We assessed the frequency of rPSC and studied risk factors for recurrent disease with special focus on IBD. We also evaluated the importance of rPSC for prognosis. MATERIALS AND METHODS All liver transplanted PSC patients in the Nordic countries between 1984 and 2007 (n = 440), identified by the Nordic Liver Transplant Registry, were studied. Data were retrieved from patients' chart reviews. Multivariable Cox regression models were used to calculate risk factors for rPSC and death. RESULTS Of the 440 patients with a follow-up time after liver transplantation of 3743 patient years, rPSC was diagnosed in 19% (n = 85). Colectomy before liver transplantation was associated with a reduced risk of rPSC (HR 0.49; 95% CI, 0.26-0.94, p = 0.033). Neither high IBD activity nor presence of IBD flares before or after liver transplantation was associated with rPSC. Treatment with tacrolimus was an independent risk factor associated with increased risk for rPSC (HR, 1.81; 95% CI, 1.15-2.86, p = 0.010). The risk of dying or needing a re-transplantation after rPSC was increased in all age groups, but highest in patients transplanted before 40 years of age (HR 7.3; 95% CI, 4.1-12.8, p = 0.0001). CONCLUSIONS This study confirms that colectomy before liver transplantation is associated with a decreased risk of rPSC. Inflammatory activity of IBD was not associated with the risk of rPSC. Tacrolimus was an independent risk factor for PSC recurrence and its use as first line immunosuppression in PSC needs further study.
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Affiliation(s)
- Lina Lindström
- a Centre for Digestive Diseases, Division of Hepatology , Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
| | - Kristin K Jørgensen
- b Department of Transplantation Medicine, Section for Gastroenterology and Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation , Oslo University Hospital Rikshospitalet , Oslo , Norway.,c Department of Gastroenterology , Akershus University Hospital , Lørenskog , Norway
| | - Kirsten M Boberg
- b Department of Transplantation Medicine, Section for Gastroenterology and Norwegian PSC Research Center, Division of Surgery, Inflammatory Diseases and Transplantation , Oslo University Hospital Rikshospitalet , Oslo , Norway.,d Institute of Clinical Medicine , University of Oslo , Oslo , Norway
| | - Maria Castedal
- e Transplant Institute , Sahlgrenska University Hospital and Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden
| | - Allan Rasmussen
- f Department of Surgery and Liver Transplantation , Rigshospitalet , Copenhagen , Denmark
| | | | - Helena Isoniemi
- g Department of Surgery , University of Helsinki and Helsinki University Hospital , Helsinki , Finland
| | - Matteo Bottai
- h Unit of Biostatistics, Institute of Environmental Medicine , Karolinska Institutet , Stockholm , Sweden
| | - Annika Bergquist
- a Centre for Digestive Diseases, Division of Hepatology , Karolinska University Hospital, Karolinska Institutet , Stockholm , Sweden
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Wijarnpreecha K, Panjawatanan P, Mousa OY, Cheungpasitporn W, Pungpapong S, Ungprasert P. Association between smoking and risk of primary sclerosing cholangitis: A systematic review and meta-analysis. United European Gastroenterol J 2018; 6:500-508. [PMID: 29881604 DOI: 10.1177/2050640618761703] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/05/2018] [Indexed: 12/15/2022] Open
Abstract
Background/Objectives Studies have suggested that smokers may have a lower risk of primary sclerosing cholangitis (PSC) although the results have been inconsistent. This systematic review and meta-analysis was conducted to summarize all available data to better characterize this association. Methods A comprehensive literature review was conducted using Medline and Embase databases through January 2018 to identify all studies that compared the risk of PSC among current/former smokers versus nonsmokers. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Seven case-control studies with 2,307,393 participants met the eligibility criteria and were included in the meta-analysis. The risk of PSC among current smokers and former smokers was significantly lower than nonsmokers with the pooled odds ratio of 0.31 (95% CI, 0.18-0.53) and 0.52 (95% CI, 0.44-0.61), respectively. The risk remained significantly lower among current smokers and former smokers compared with nonsmokers even when only patients with PSC without inflammatory bowel disease were included. Conclusions A significantly decreased risk of PSC among current and former smokers was demonstrated in this study.
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Affiliation(s)
- Karn Wijarnpreecha
- 1Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA
| | | | - Omar Y Mousa
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Wisit Cheungpasitporn
- 4Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Surakit Pungpapong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Patompong Ungprasert
- 5Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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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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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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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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Abstract
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease affecting intra- and extrahepatic bile ducts, primarily the large biliary ducts. Clinical manifestations are broad, and the spectrum encompasses asymptomatic cholestasis, icteric cholangitis with pruritis, cirrhosis, and cholangiocarcinoma. Though rare, PSC has a propensity to affect young to middle-aged males and is strongly associated with inflammatory bowel disease. There is an unmet need for effective medical treatments for PSC, and to date, the only curative therapy is liver transplantation reserved for those with end-stage liver disease. This article addresses the diagnostic and management challenges of PSC, with a succinct analysis of existing therapies, their limitations, and a glimpse into the future of the management of this multifaceted pathologic entity.
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Affiliation(s)
- Sanjeev Sirpal
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), University of Montreal, Montreal, QC
| | - Natasha Chandok
- Department of Medicine, University of Western Ontario, London, ON, Canada
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41
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Grammatikopoulos T, Thompson RJ. Reply to: "Doublecortin domain containing protein 2 (DCDC2) genetic variants in primary sclerosing cholangitis". J Hepatol 2017; 67:652-653. [PMID: 28461131 DOI: 10.1016/j.jhep.2017.04.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Accepted: 04/22/2017] [Indexed: 12/04/2022]
Affiliation(s)
- Tassos Grammatikopoulos
- Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK; Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London, London, UK.
| | - Richard J Thompson
- Paediatric Liver, GI & Nutrition Centre, King's College Hospital, London, UK; Institute of Liver Studies, Division of Transplantation Immunology and Mucosal Biology, King's College London, London, UK
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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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Filipec Kanizaj T, Mijic M. Inflammatory bowel disease in liver transplanted patients. World J Gastroenterol 2017; 23:3214-3227. [PMID: 28566881 PMCID: PMC5434427 DOI: 10.3748/wjg.v23.i18.3214] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2017] [Revised: 04/13/2017] [Accepted: 04/21/2017] [Indexed: 02/06/2023] Open
Abstract
Most common hepatobiliary manifestation of inflammatory bowel disease (IBD) are primary sclerosing cholangitis (PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation (LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Anti-tumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic disease leading to fibrotic scarring of the intrahepatic and extrahepatic bile ducts, causing considerable morbidity and mortality via the development of cholestatic liver cirrhosis, concurrent IBD and a high risk of bile duct cancer. Expectations have been high that genetic studies would determine key factors in PSC pathogenesis to support the development of effective medical therapies. Through the application of genome-wide association studies, a large number of disease susceptibility genes have been identified. The overall genetic architecture of PSC shares features with both autoimmune diseases and IBD. Strong human leukocyte antigen gene associations, along with several susceptibility genes that are critically involved in T-cell function, support the involvement of adaptive immune responses in disease pathogenesis, and position PSC as an autoimmune disease. In this Review, we survey the developments that have led to these gene discoveries. We also elaborate relevant interpretations of individual gene findings in the context of established disease models in PSC, and propose relevant translational research efforts to pursue novel insights.
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45
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Restellini S, Chazouillères O, Frossard JL. Hepatic manifestations of inflammatory bowel diseases. Liver Int 2017; 37:475-489. [PMID: 27712010 DOI: 10.1111/liv.13265] [Citation(s) in RCA: 52] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Accepted: 09/27/2016] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel diseases are associated with various hepatobiliary disorders, reported both in Crohn's disease and ulcerative colitis. They may occur at any moment in the natural course of the disease. The prevalence of liver dysfunction rises from 3% to 50% accordingly to definitions used in different studies. Fatty liver is considered as the most common hepatobiliary complication in inflammatory bowel diseases while primary sclerosing cholangitis is the most specific one. Less frequently, inflammatory bowel diseases-associated hepatobiliary disorders include: autoimmune hepatitis/ primary sclerosing cholangitis overlap syndrome, IgG4-associated cholangiopathy, primary biliary cholangitis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis and liver abscess. The spectrum of these manifestations varies according to the type of inflammatory bowel diseases. Treatments of inflammatory bowel diseases may cause liver toxicity, although incidence of serious complications remains low. However, early diagnosis of drug-induced liver injury is of major importance as it affects future clinical management. When facing abnormal liver tests, clinicians should undertake a full diagnostic work-up in order to determine whether the hepatic abnormalities are related to the inflammatory bowel diseases or not. Management of hepatic manifestations in inflammatory bowel diseases usually involves both hepatologists and gastroenterologists because of the complexity of some situations.
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Affiliation(s)
- Sophie Restellini
- Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève, Genève, Suisse
| | - Olivier Chazouillères
- Division d'Hépatologie, Centre de Référence des Maladies Inflammatoires des Voies Biliaires, et Université de Sorbonne, UPMC Univ Paris 06, UMR_S 938, CDR Saint-Antoine, AP-HP, Hôpital Saint-Antoine, Paris, France
| | - Jean-Louis Frossard
- Service de Gastroentérologie et Hépatologie, Hôpitaux Universitaires de Genève, Genève, Suisse
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McCarty TR, Afinogenova Y, Njei B. Use of Wireless Capsule Endoscopy for the Diagnosis and Grading of Esophageal Varices in Patients With Portal Hypertension: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51:174-182. [PMID: 27548729 PMCID: PMC5218864 DOI: 10.1097/mcg.0000000000000589] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Esophageal variceal bleeding is a severe complication of portal hypertension with significant morbidity and mortality. Although traditional screening and grading of esophageal varices has been performed by endogastroduodenoscopy (EGD), wireless video capsule endoscopy provides a minimally invasive alternative that may improve screening and surveillance compliance. AIM OF THE STUDY The aim of the study was to perform a systematic review and structured meta-analysis of all eligible studies to evaluate the efficacy of wireless capsule endoscopy for screening and diagnosis of esophageal varices among patients with portal hypertension. METHODS Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were performed through December 2015. Bivariate and hierarchical models were used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence region. Bias of included studies was assessed using the quality assessment of diagnostic accuracy studies-2. RESULTS Seventeen studies from 2005 to 2015 were included in this meta-analysis (n=1328). The diagnostic accuracy of wireless capsule endoscopy in the diagnosis of esophageal varices was 90% [95% confidence interval (CI), 0.88-0.93]. The diagnostic pooled sensitivity and specificity were 83% (95% CI, 0.76-0.89) and 85% (95% CI, 0.75-0.91), respectively. The diagnostic accuracy of wireless capsule endoscopy for the grading of medium to large varices was 92% (95% CI, 0.90-0.94). The pooled sensitivity and specificity were 72% (95% CI, 0.54-0.85) and 91% (95% CI, 0.86-0.94), respectively, for the grading of medium to large varices. The use of capsule demonstrated only mild adverse events. A sensitivity analysis limited to only high quality studies revealed similar results. DISCUSSION Wireless esophageal capsule endoscopy is well tolerated and safe in patients with liver cirrhosis and suspicion of portal hypertension. The sensitivity of capsule endoscopy is not currently sufficient to replace EGD as a first exploration in these patients, but given its high accuracy, it may have a role in cases of refusal or contraindication to EGD.
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Affiliation(s)
- Thomas R. McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Yuliya Afinogenova
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - Basile Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
- Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
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Njei B, McCarty TR, Varadarajulu S, Navaneethan U. Systematic review with meta-analysis: endoscopic retrograde cholangiopancreatography-based modalities for the diagnosis of cholangiocarcinoma in primary sclerosing cholangitis. Aliment Pharmacol Ther 2016; 44:1139-1151. [PMID: 27696456 DOI: 10.1111/apt.13817] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2016] [Revised: 05/18/2016] [Accepted: 09/13/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND The accuracy of current endoscopic modalities for diagnosing cholangiocarcinoma in primary sclerosing cholangitis (PSC) is suboptimal. AIM To evaluate the comparative effectiveness of endoscopic retrograde cholangiopancreatography (ERCP)-based modalities, independently or in combination, for the diagnosis of cholangiocarcinoma in patients with PSC-induced biliary strictures. METHODS Searches of PubMed, EMBASE, Web of Science and the Cochrane Library databases were performed through December 2015. Measured outcomes included sensitivity and specificity of all diagnostic modalities independently or in combination. A bivariate model was used to compute the pooled sensitivity and specificity, and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI). A logistic regression model was used to impute the incremental performance of combining two diagnostic tests. RESULTS Twenty-one studies met inclusion criteria: 13 on bile duct brushing for cytology, 7 on fluorescence in situ hybridisation (FISH), 2 on probe-based confocal laser endomicroscopy, and 4 on single-operator cholangioscopy with targeted biopsies. Single-operator cholangioscopy with targeted biopsies was the most accurate diagnostic modality at 96% (95% CI, 94-97%). The pooled sensitivity and specificity of single-operator cholangioscopy for diagnosis of cholangiocarcinoma in patients with PSC was 65% (95% CI, 35-87%) and 97% (95% CI, 87-99%), respectively. The pooled diagnostic odds ratio to detect cholangiocarcinoma was 59 (95% CI, 10-341). CONCLUSIONS Single-operator cholangioscopy with targeted biopsies appears to be the most accurate ERCP-based modality for diagnosing cholangiocarcinoma in primary sclerosing cholangitis. However, future large, well-designed comparative diagnostic studies are warranted to validate these findings.
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Affiliation(s)
- B Njei
- Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.,Investigative Medicine Program, Yale Center of Clinical Investigation, New Haven, CT, USA
| | - T R McCarty
- Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA
| | - S Varadarajulu
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
| | - U Navaneethan
- Center for Interventional Endoscopy, Florida Hospital, Orlando, FL, USA
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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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50
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Ali AH, Carey EJ, Lindor KD. The management of autoimmunity in patients with cholestatic liver diseases. Expert Rev Gastroenterol Hepatol 2016; 10:73-91. [PMID: 26523975 DOI: 10.1586/17474124.2016.1095088] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Cholestatic liver diseases are rare diseases that often lead to cirrhosis and its consequent complications. In addition to liver-related morbidity, patients with cholestatic liver diseases often suffer from autoimmune diseases that affect several organs and tissues. The robust and efficient data collection and collaboration between hepatologists and rheumatologists have led to significant advancements in understanding the relationship between the cholestatic liver diseases and associated autoimmune diseases. In this paper, we discuss the cholestatic liver diseases (primary biliary cirrhosis, primary sclerosing cholangitis and immunoglobulin G4 associated cholangitis) and associated autoimmune diseases.
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Affiliation(s)
- Ahmad H Ali
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Elizabeth J Carey
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA
| | - Keith D Lindor
- a 1 Division of Gastroenterology and Hepatology, Mayo Clinic, Phoenix, AZ, USA.,b 2 Arizona State University, College of Health Solutions, Phoenix, AZ, USA
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