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Das TS, Ho K, Udaikumar J, Chen B, Delau O, Shaukat A, Jacobson I, Sarwar R. Risk of colorectal cancer in patients with primary sclerosing cholangitis and concomitant inflammatory bowel disease compared with primary sclerosing cholangitis only. Hepatol Res 2024; 54:807-816. [PMID: 38419394 DOI: 10.1111/hepr.14029] [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: 12/09/2023] [Revised: 02/06/2024] [Accepted: 02/08/2024] [Indexed: 03/02/2024]
Abstract
AIM Primary sclerosing cholangitis (PSC) increases the risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients; however, there is a paucity of literature to suggest PSC alone as an independent risk factor for CRC. We aimed to determine if PSC is an independent risk factor for CRC in a large tertiary care medical center. Optimizing screening intervals is of great importance, given the burden and risks associated with a lifetime of colonoscopy screening. METHODS This retrospective cohort study consists of patients diagnosed with PSC preceding IBD (PSC-IBD) and PSC-only before January 6, 2023 from a large, tertiary, academic medical center. Patients diagnosed with IBD concurrently or before PSC were excluded to reduce IBD's impact on CRC risk. Demographic data and colonoscopy findings were collected and assessed. RESULTS Overall, 140 patients from all NYU Langone Health clinical settings were included. Patients with PSC-IBD were more likely to be diagnosed with CRC (23.3% vs. 1.8%, p < 0.01) and either low-grade or uncharacterized dysplasia (16.7% vs. 0.0%, p < 0.01) compared with those with PSC-only. Among PSC-only patients, the estimated CRC risk was significantly elevated compared with that expected of the standard NYU Langone population (SIR 9.2, 95% CI 1.1, 33.2). CONCLUSIONS Our study revealed a significantly heightened CRC risk in PSC-IBD patients compared with those with PSC-only. Importantly, individuals with PSC-only also face a greater CRC risk compared with the general population. Individuals with PSC-alone may require extended screening and surveillance colonoscopy intervals compared with those with PSC-IBD, yet still require more frequent monitoring than screening guidelines recommend for the general population.
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Affiliation(s)
- Taranika Sarkar Das
- Department of Medicine, NYU Langone Medical Center, New York City, New York, USA
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York City, New York, USA
| | - Kimberly Ho
- NYU Grossman School of Medicine, New York City, New York, USA
| | - Jahnavi Udaikumar
- Department of Medicine, NYU Langone Medical Center, New York City, New York, USA
| | - Bryan Chen
- NYU Grossman School of Medicine, New York City, New York, USA
| | - Olivia Delau
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York City, New York, USA
| | - Aasma Shaukat
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York City, New York, USA
| | - Ira Jacobson
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York City, New York, USA
| | - Raiya Sarwar
- Division of Gastroenterology and Hepatology, NYU Langone Medical Center, New York City, New York, USA
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2
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Bowlus CL, Arrivé L, Bergquist A, Deneau M, Forman L, Ilyas SI, Lunsford KE, Martinez M, Sapisochin G, Shroff R, Tabibian JH, Assis DN. AASLD practice guidance on primary sclerosing cholangitis and cholangiocarcinoma. Hepatology 2023; 77:659-702. [PMID: 36083140 DOI: 10.1002/hep.32771] [Citation(s) in RCA: 125] [Impact Index Per Article: 62.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/26/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology , University of California Davis Health , Sacramento , California , USA
| | | | - Annika Bergquist
- Karolinska Institutet , Karolinska University Hospital , Stockholm , Sweden
| | - Mark Deneau
- University of Utah , Salt Lake City , Utah , USA
| | - Lisa Forman
- University of Colorado , Aurora , Colorado , USA
| | - Sumera I Ilyas
- Mayo Clinic College of Medicine and Science , Rochester , Minnesota , USA
| | - Keri E Lunsford
- Rutgers University-New Jersey Medical School , Newark , New Jersey , USA
| | - Mercedes Martinez
- Vagelos College of Physicians and Surgeons , Columbia University , New York , New York , USA
| | | | | | - James H Tabibian
- David Geffen School of Medicine at UCLA , Los Angeles , California , USA
| | - David N Assis
- Yale School of Medicine , New Haven , Connecticut , USA
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3
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Little R, Kamath BM, Ricciuto A. Liver Disease in Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:129-149. [DOI: 10.1007/978-3-031-14744-9_11] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 152] [Impact Index Per Article: 50.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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5
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Akiyama S, Fukuda S, Steinberg JM, Suzuki H, Tsuchiya K. Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases. World J Gastroenterol 2022; 28:2843-2853. [PMID: 35978883 PMCID: PMC9280738 DOI: 10.3748/wjg.v28.i25.2843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/10/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.
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Affiliation(s)
- Shintaro Akiyama
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Soma Fukuda
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Joshua M Steinberg
- Inflammatory Bowel Disease, Gastroenterology of the Rockies, Denver, CO 80218, United States
| | - Hideo Suzuki
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
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6
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Pugliese N, Arcari I, Aghemo A, Lania AG, Lleo A, Mazziotti G. Osteosarcopenia in autoimmune cholestatic liver diseases: Causes, management, and challenges. World J Gastroenterol 2022; 28:1430-1443. [PMID: 35582674 PMCID: PMC9048470 DOI: 10.3748/wjg.v28.i14.1430] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/05/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.
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Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ivan Arcari
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Andrea G Lania
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Gherardo Mazziotti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
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7
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Yano K, Moroi R, Shiga H, Tarasawa K, Shimoyama Y, Kuroha M, Hamada S, Kakuta Y, Fushimi K, Fujimori K, Kinouchi Y, Masamune A. Analysis of the disease activity of ulcerative colitis with and without concomitant primary sclerosing cholangitis: An investigation using a nationwide database in Japan. JGH Open 2022; 6:50-56. [PMID: 35071788 PMCID: PMC8762614 DOI: 10.1002/jgh3.12693] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Revised: 11/22/2021] [Accepted: 12/01/2021] [Indexed: 11/07/2022]
Abstract
Aims Primary sclerosing cholangitis (PSC) is a relatively common complication of ulcerative colitis (UC). Only a few studies have investigated the impact of PSC on the clinical course of UC, and their conclusions are contradictory. Therefore, we aimed to compare the disease activity of UC with and without PSC. Methods and Results We collected UC patient data using the Diagnosis Procedure Combination database system in Japan and classified eligible admissions into two groups based on their diagnosis of either UC alone or UC associated with PSC. We then compared therapeutic details (medical treatment and surgery) between the two groups. Multivariable logistic regression analysis and propensity score matching was also performed. The rates of systemic steroid injection and infliximab administration in patients with PSC were lower than those in patients without PSC (21% vs. 28%, P = 0.012, 9.6% vs. 16%, P = 0.01, respectively). The rates of surgery, colorectal cancer, duration of hospital stay, and in-hospital mortality did not differ between the two groups. Multivariable analysis revealed that concomitant PSC was a clinical factor that reduced the odds of systemic steroid injection (odds ratio [OR] = 0.66, 95% confidence interval [CI]: 0.49-0.90, P = 0.008) and infliximab (OR = 0.48, 95% CI: 0.32-0.74, P = 0.0008) administration. Conclusion UC patients with PSC might have less UC disease activity than those with UC alone.
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Affiliation(s)
- Kota Yano
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Rintaro Moroi
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Hisashi Shiga
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Kunio Tarasawa
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | - Yusuke Shimoyama
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Masatake Kuroha
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Shin Hamada
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Kiyohide Fushimi
- Department of Health Policy and Informatics Tokyo Medical and Dental University Graduate School of Medicine Bunkyo Japan
| | - Kenji Fujimori
- Department of Health Administration and Policy Tohoku University Graduate School of Medicine Sendai Japan
| | - Yoshitaka Kinouchi
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Department of Internal Medicine Tohoku University Graduate School of Medicine Sendai Japan
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Ponsioen CY, Assis DN, Boberg KM, Bowlus CL, Deneau M, Thorburn D, Aabakken L, Färkkilä M, Petersen B, Rupp C, Hübscher SG. Defining Primary Sclerosing Cholangitis: Results From an International Primary Sclerosing Cholangitis Study Group Consensus Process. Gastroenterology 2021; 161:1764-1775.e5. [PMID: 34384749 DOI: 10.1053/j.gastro.2021.07.046] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2021] [Accepted: 07/29/2021] [Indexed: 12/24/2022]
Affiliation(s)
- Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, the Netherlands
| | - David N Assis
- Department of Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut
| | - Kirsten M Boberg
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis School of Medicine, Sacramento, California
| | - Mark Deneau
- University of Utah and Intermountain Primary Children's Hospital, Salt Lake City, Utah
| | - Douglas Thorburn
- Sheila Sherlock Liver Centre, Royal Free Hospital and Institute for Liver and Digestive Health, University College London, London, United Kingdom; ERN RARE Liver, Hamburg, Germany
| | - Lars Aabakken
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section for Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine, and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; ERN RARE Liver, Hamburg, Germany
| | - Martti Färkkilä
- Abdominal Center, Helsinki University Hospital, Helsinki, Finland; ERN RARE Liver, Hamburg, Germany
| | - Bret Petersen
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Christian Rupp
- Department of Internal Medicine IV, Gastroenterology, and Hepatology, University Hospital Heidelberg, Heidelberg, Germany
| | - Stefan G Hübscher
- Institute of Immunology and Immunotherapy, University of Birmingham and, Department of Cellular Pathology, Queen Elizabeth Hospital, Birmingham, United Kingdom
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9
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Ribaldone DG, Imperatore N, Le Grazie M, Furfaro F, Balestrieri P, De Blasio F, Fagoonee S, Mosso E, Boano V, Reggio D, Sarli E, Castiglione F, Milla M, Vecchi M, Saracco GM, Salizzoni M, Romagnoli R, Fiorino G, Astegiano M. Inflammatory bowel disease course in liver transplant versus non-liver transplant patients for primary sclerosing cholangitis: LIVIBD, an IG-IBD study. Dig Liver Dis 2021; 53:712-716. [PMID: 32972831 DOI: 10.1016/j.dld.2020.09.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 09/15/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Data regarding the effect of orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD) course are scarce and conflicting. AIMS To compare the incidence of refractory IBD in two groups (OLT and non-OLT) of patients affected by IBD and PSC. METHODS An observational, multicentre, cohort retrospective study was conducted by the Italian Group for the study of IBD in Italy. The primary outcome was the need for biologic therapy or bowel resection for medically refractory IBD or hospitalization due to IBD relapse during the follow-up. Secondary outcomes were rate of colonic dysplasia, colorectal cancer, other solid tumours, lymphoma. RESULTS Eighty-four patients were included in the study. The primary outcome was not different between OLT and non-OLT groups (11/27, 40.7%, versus 20/57, 35.1%, respectively, p = 0.62). The lymphoma and other tumours (thyroid cancer, kidney cancer, ileal tumour, ovarian cancer, cervical cancer) rates were significantly higher in the OLT group (p = 0.04 and p = 0.005, respectively), at the limit of statistical significance for high-grade colonic dysplasia (p = 0.06). CONCLUSION OLT in patients affected by IBD and PSC is not a risk factor for a more severe IBD course, but it is associated with a higher occurrence of cancer.
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Affiliation(s)
| | - Nicola Imperatore
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy; Gastroenterology and Endoscopy Unit, AORN Antonio Cardarelli, Naples, Italy
| | - Marco Le Grazie
- IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence, Italy
| | - Federica Furfaro
- Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy
| | | | - Federico De Blasio
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Sharmila Fagoonee
- Institute of Biostructure and Bioimaging (CNR), Molecular Biotechnology Center, Turin, Italy
| | - Elena Mosso
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Valentina Boano
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Dario Reggio
- General Surgery 2U, Liver Transplant Center, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Ennio Sarli
- Italian Group for the study of Inflammatory Bowel Disease IG-IBD, Florence, Italy
| | - Fabiana Castiglione
- Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy
| | - Monica Milla
- IBD Referral Center, Gastroenterology Department, Careggi University Hospital, Florence, Italy
| | - Maurizio Vecchi
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, Torino, Italy
| | - Mauro Salizzoni
- General Surgery 2U, Liver Transplant Center, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Renato Romagnoli
- General Surgery 2U, Liver Transplant Center, Department of Surgical Sciences, University of Turin, Turin, Italy
| | - Gionata Fiorino
- Humanitas Clinical and Research Center - IRCCS, Rozzano, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
| | - Marco Astegiano
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, Turin, Italy
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10
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Attauabi M, Zhao M, Bendtsen F, Burisch J. Systematic Review with Meta-analysis: The Impact of Co-occurring Immune-mediated Inflammatory Diseases on the Disease Course of Inflammatory Bowel Diseases. Inflamm Bowel Dis 2021; 27:927-939. [PMID: 32628745 DOI: 10.1093/ibd/izaa167] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel diseases (IBDs) are at risk of developing a variety of other immune-mediated inflammatory diseases (IMIDs). The influence of co-occurring IMIDs on the disease course of IBD remains unknown. The aim of this study was therefore to conduct a systematic review and meta-analysis of the impact of IMIDs on phenotypic presentation and outcome in patients with IBD. METHODS PubMed and Embase were searched from their earliest records through December 2018 and updated in October 2019 for studies reporting proportions or ratios of IBD-related disease outcomes in patients with and without co-occurring IMIDs. Meta-analyses were performed to estimate summary proportions and risks of the main outcomes. PRISMA guidelines were used, and study quality was assessed according to the Newcastle-Ottawa Scale. RESULTS A total of 93 studies were identified, comprising 16,064 IBD patients with co-occurring IMIDs and 3,451,414 IBD patients without IMIDs. Patients with IBD and co-occurring IMIDs were at increased risk of having extensive colitis or pancolitis (risk ratio, 1.38; 95% Cl, 1.25-1.52; P < 0.01, I2 = 86%) and receiving IBD-related surgeries (risk ratio, 1.17; 95% Cl, 1.01-1.36; P = 0.03; I2 = 85%) compared with patients without IMIDs. Co-occurrence of IMIDs other than primary sclerosing cholangitis in patients with IBD was associated with an increased risk of receiving immunomodulators (risk ratio, 1.15; 95% Cl, 1.06-1.24; P < 0.01; I2 = 60%) and biologic therapies (risk ratio, 1.19; 95% Cl, 1.08-1.32; P < 0.01; I2 = 53%). CONCLUSION This meta-analysis found that the presence of co-occurring IMIDs influences the disease course of IBD, including an increased risk of surgery and its phenotypical expression.
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Affiliation(s)
- Mohamed Attauabi
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mirabella Zhao
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
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11
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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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12
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Aranake-Chrisinger J, Dassopoulos T, Yan Y, Nalbantoglu ILK. Primary sclerosing cholangitis associated colitis: Characterization of clinical, histologic features, and their associations with liver transplantation. World J Gastroenterol 2020; 26:4126-4139. [PMID: 32821074 PMCID: PMC7403798 DOI: 10.3748/wjg.v26.i28.4126] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/08/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) associated inflammatory bowel disease (IBD) is a unique form of IBD (PSC-IBD) with distinct clinical and histologic features from ulcerative colitis (UC) and Crohn disease (CD). In patients with PSC and IBD, the severity of the two disease processes may depend on each other.
AIM To study the histologic and clinical features of PSC patients with and without IBD.
METHODS We assessed specimens from patients with UC (n = 28), CD (n = 10), PSC and UC (PSC-UC; n = 26); PSC and CD (PSC-CD; n = 6); and PSC and no IBD (PSC-no IBD; n = 4) between years 1999-2013. PSC-IBD patients were matched to IBD patients without PSC by age and colitis duration. Clinical data including age, gender, age at IBD and PSC diagnoses, IBD duration, treatment, follow-up, orthotopic liver transplantation (OLT) were noted.
RESULTS PSC-UC patients had more isolated right-sided disease (P = 0.03), and less active inflammation in left colon, rectum (P = 0.03 and P = 0.0006), and overall (P = 0.0005) compared to UC. They required less steroids (P = 0.01) and fewer colectomies (P = 0.03) than UC patients. The PSC-CD patients had more ileitis and less rectal involvement compared to PSC-UC and CD. No PSC-CD patients required OLT compared to 38% of PSC-UC (P = 0.1). PSC-IBD (PSC-UC and PSC-CD) patients with OLT had severe disease in the left colon and rectum (P = 0.04).
CONCLUSION PSC-UC represents a distinct form of IBD. The different disease phenotype in PSC-IBD patients with OLT may support liver-gut axis interaction, however warrants clinical attention and further research.
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Affiliation(s)
- John Aranake-Chrisinger
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | | | - Yan Yan
- Departments of Surgery and Biostatistics, Washington University in St. Louis, School of Medicine, MO 63110, United States
| | - ILKe Nalbantoglu
- Department of Anatomic Pathology, Yale University School of Medicine, New Haven, CT 06525, United States
- Department of Pathology and Immunology, Lauren V. Ackerman Laboratory of Surgical Pathology, Washington University in St. Louis, School of Medicine, MO 63110, United States
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13
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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] [Received: 12/22/2018] [Accepted: 01/23/2019] [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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14
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Khan N, Trivedi C, Shah Y, Cole E, Lewis J, Yang YX. The Natural History of Newly Diagnosed Ulcerative Colitis in Patients with Concomitant Primary Sclerosing Cholangitis. Inflamm Bowel Dis 2018; 24:2062-2067. [PMID: 29697792 DOI: 10.1093/ibd/izy106] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis (PSC) is commonly associated with ulcerative colitis (UC). Our aim was to compare the course of disease in patients with UC-PSC and UC alone in a nationwide cohort. METHODS We conducted a retrospective cohort study among nation-wide Veterans Affairs (VA) patients newly diagnosed with UC to determine the association between PSC status and clinical outcomes related to UC disease course. This study was divided into 2 groups of patients: (1) The incident UC-PSC group and (2) the incident UC-alone group. Follow-up began at the time of index colonoscopy that diagnosed UC and ended at the first occurrence of the respective outcome for the regression analysis of the following censoring events: (1) colectomy, (2) death, (3) end of follow-up, and (4 lost to follow-up. RESULTS The analysis included 836 UC patients without PSC and 74 UC-PSC patients. In univariate comparisons, PSC patients were more likely to have more extensive UC than those without PSC. In a multivariable Cox regression analysis adjusting for sex, age at UC diagnosis, race, severity of UC, and extent of UC, PSC status was not associated with the risk of colectomy for UC, increased risk of receiving ≥ 2 courses of steroids for UC, or with the risk of receiving immunomodulators for UC. CONCLUSION UC-PSC patients do not have a more benign disease course than UC patients without PSC. UC-PSC patients may have a modestly increased risk for multiple courses of steroids, which may be mediated by more extensive colonic involvement.
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Affiliation(s)
- Nabeel Khan
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA.,Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Guardian Drive, PA, USA
| | - Chinmay Trivedi
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA
| | - Yash Shah
- Department of Internal Medicine, Icahn School of Medicine at Mount Sinai, James J. Peters VA Medical Center, NY, USA
| | - Elisabeth Cole
- Children's Hospital of Pittsburgh of UPMC, One Children's Hospital Drive, PA, USA
| | - James Lewis
- Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
| | - Yu-Xiao Yang
- Section of Gastroenterology, Corporal Michael J. Crescenz Medical Center, Pennsylvania, USA.,Section of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Guardian Drive, PA, USA
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15
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Shah SC, Ten Hove JR, Castaneda D, Palmela C, Mooiweer E, Colombel JF, Harpaz N, Ullman TA, van Bodegraven AA, Jansen JM, Mahmmod N, van der Meulen-de Jong AE, Ponsioen CY, van der Woude CJ, Oldenburg B, Itzkowitz SH, Torres J. High Risk of Advanced Colorectal Neoplasia in Patients With Primary Sclerosing Cholangitis Associated With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2018; 16:1106-1113.e3. [PMID: 29378311 DOI: 10.1016/j.cgh.2018.01.023] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Revised: 12/20/2017] [Accepted: 01/12/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC, termed PSC-IBD) are at increased risk for colorectal cancer, but their risk following a diagnosis of low-grade dysplasia (LGD) is not well described. We aimed to determine the rate of advanced colorectal neoplasia (aCRN), defined as high-grade dysplasia and/or colorectal cancer, following a diagnosis of indefinite dysplasia or LGD in this population. METHODS We performed a retrospective, longitudinal study of 1911 patients with colonic IBD (293 with PSC and 1618 without PSC) who underwent more than 2 surveillance colonoscopies from 2000 through 2015 in The Netherlands or the United States (9265 patient-years of follow-up evaluation). We collected data on clinical and demographic features of patients, as well as data from each surveillance colonoscopy and histologic report. For each surveillance colonoscopy, the severity of active inflammation was documented. The primary outcome was a diagnosis of aCRN during follow-up evaluation. We also investigated factors associated with aCRN in patients with or without a prior diagnosis of indefinite dysplasia or LGD. RESULTS Patients with PSC-IBD had a 2-fold higher risk of developing aCRN than patients with non-PSC IBD. Mean inflammation scores did not differ significantly between patients with PSC-IBD (0.55) vs patients with non-PSC IBD (0.56) (P = .89), nor did proportions of patients with LGD (21% of patients with PSC-IBD vs 18% of patients with non-PSC IBD) differ significantly (P = .37). However, the rate of aCRN following a diagnosis of LGD was significantly higher in patients with PSC-IBD (8.4 per 100 patient-years) than patients with non-PSC IBD (3.0 per 100 patient-years; P = .01). PSC (adjusted hazard ratio [aHR], 2.01; 95% CI, 1.09-3.71), increasing age (aHR 1.03; 95% CI, 1.01-1.05), and active inflammation (aHR, 2.39; 95% CI, 1.63-3.49) were independent risk factors for aCRN. Dysplasia was more often endoscopically invisible in patients with PSC-IBD than in patients with non-PSC IBD. CONCLUSIONS In a longitudinal study of almost 2000 patients with colonic IBD, PSC remained a strong independent risk factor for aCRN. Once LGD is detected, aCRN develops at a higher rate in patients with PSC and is more often endoscopically invisible than in patients with only IBD. Our findings support recommendations for careful annual colonoscopic surveillance for patients with IBD and PSC, and consideration of colectomy once LGD is detected.
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Affiliation(s)
- Shailja C Shah
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Gastroenterology and Hepatology, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Joren R Ten Hove
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Daniel Castaneda
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Carolina Palmela
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Erik Mooiweer
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jean-Frédéric Colombel
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Noam Harpaz
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Thomas A Ullman
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ad A van Bodegraven
- Department of Gastroenterology and Hepatology, Vrije Universiteit Medical Center Amsterdam, Amsterdam, The Netherlands
| | - Jeroen M Jansen
- Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis Amsterdam, Amsterdam, The Netherlands
| | - Nofel Mahmmod
- Department of Gastroenterology and Hepatology, St Antonius Hospital Nieuwegein, Nieuwegein, The Netherlands
| | | | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Amsterdam Medical Center, Amsterdam, The Netherlands
| | - Christine J van der Woude
- Department of Gastroenterology and Hepatology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Bas Oldenburg
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Steven H Itzkowitz
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Joana Torres
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Surgical Department, Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal.
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16
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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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17
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Abstract
PURPOSE OF REVIEW To review the characteristics of IBD and PSC that occur in association, as well as their reciprocal influences on disease evolution, in adult and pediatric populations. RECENT FINDINGS IBD co-existing with PSC is genetically and clinically distinct from IBD alone. It is frequently characterized by pancolitis, rectal sparing, and possibly backwash ileitis, as well as a threefold increased risk of colorectal dysplasia. Adults and children with colitis and PSC appear to be at increased risk of active endoscopic and histologic disease in the absence of symptoms compared to individuals without PSC. PSC occurring with Crohn's disease has been observed to be less severe than PSC co-existing with ulcerative colitis, independent of its association with small duct disease. Recent studies suggest that colectomy is associated with a decreased risk of recurrent PSC after liver transplantation, challenging the traditional teaching that PSC and IBD evolve independently. While much about the gut-liver axis in PSC-IBD remains poorly understood, the IBD associated with PSC has a unique phenotype, of which subclinical inflammation is an important component. Additional research is needed to characterize further the potentially protective role of colectomy against recurrent PSC post-liver transplantation and to investigate the influence of IBD control and/or colectomy on PSC progression.
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Affiliation(s)
- Amanda Ricciuto
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada.
| | - Binita M Kamath
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada
| | - Anne M Griffiths
- Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, M5G1X8, Canada
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18
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Tabibian JH, Bowlus CL. Primary sclerosing cholangitis: A review and update. LIVER RESEARCH (BEIJING, CHINA) 2017; 1:221-230. [PMID: 29977644 PMCID: PMC6028044 DOI: 10.1016/j.livres.2017.12.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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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19
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Cardile S, Alterio T, Candusso M, Pietrobattista A, Liccardo D, Basso MS, Papadatou B, Bracci F, Knafelz D, Torre G. Autoimmune liver diseases and inflammatory bowel diseases in children: current issues and future perspectives. Scand J Gastroenterol 2017; 52:662-667. [PMID: 28281846 DOI: 10.1080/00365521.2017.1298833] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Inflammatory bowel diseases (IBDs) represent a group of intestinal disorders with a chronic and relapsing inflammation of the gut, and with a potential risk of systemic involvement of other organs and systems. Over the pediatric age, an incidence higher than 20% of developing extraintestinal manifestation during follow-up has been reported. The liver and the biliary system are frequently involved, and primary sclerosing cholangitis (PSC) is the most predominant entity with an incidence rate of 6.4-7.8% in children. PSC recognizes a multifactorial pathogenesis, and so far a not fully known mechanism for this association. The peculiar phenotype and the distinct clinical course of patients with IBD and PSC-associated make this 'linkage' an attractive study model to better understand mechanisms underlying these diseases. Approaching to these patients is complex and multidisciplinary, and a unique therapeutic strategy has not been standardized yet. New medications are being studied; however, further studies are needed to fully understand the pathogenesis and to improve the care of these patients. The aim of this paper is to review the recent literature regarding hepatobiliary involvement in IBD patients, with particular attention to PSC, and to provide the latest information for a correct diagnosis and appropriate management.
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Affiliation(s)
- Sabrina Cardile
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Tommaso Alterio
- b Department of Pediatrics , University of Messina , Messina , Italy
| | - Manila Candusso
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Andrea Pietrobattista
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Daniela Liccardo
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Maria Sole Basso
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Bronislava Papadatou
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Fiammetta Bracci
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Daniela Knafelz
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
| | - Giuliano Torre
- a Hepatology, Gastroenterology and Nutrition Unit , Bambino Gesù Children's Hospital , Rome , Italy
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20
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Liu K, Strasser SI, Koorey DJ, Leong RW, Solomon M, McCaughan GW. Interactions between primary sclerosing cholangitis and inflammatory bowel disease: implications in the adult liver transplant setting. Expert Rev Gastroenterol Hepatol 2017. [PMID: 28627935 DOI: 10.1080/17474124.2017.1343666] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease which is associated with inflammatory bowel disease (IBD) in most cases. As there is currently no medical therapy which alters the natural history of PSC, liver transplantation may be required. Areas covered: We searched for articles in PubMed and critically reviewed current literature on the interrelationship between PSC and IBD with a specific focus on considerations for patients in the liver transplant setting. Expert commentary: PSC is an uncommon disease which limits available studies to be either retrospective or contain relatively small numbers of patients. Based on observations from these studies, the behavior and complications of PSC and IBD impact on each other both before and after a liver transplant. Both these autoimmune conditions and their associated cancer risk also influence patient selection for transplantation and may be impacted by immunosuppression use post-transplant. Hence, a complex interplay exists between PSC, IBD and liver transplantation which requires clarification with ongoing research.
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Affiliation(s)
- Ken Liu
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
| | - Simone I Strasser
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - David J Koorey
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Rupert W Leong
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,d Gastroenterology and Liver Services , Concord Hospital , Sydney , NSW , Australia
| | - Michael Solomon
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,e Department of Colorectal Surgery , Royal Prince Alfred Hospital , Sydney , NSW , Australia
| | - Geoffrey W McCaughan
- a Sydney Medical School , The University of Sydney , Sydney , NSW , Australia.,b AW Morrow Gastroenterology and Liver Centre , Royal Prince Alfred Hospital , Sydney , NSW , Australia.,c Liver Injury and Cancer Program, Centenary Institute , The University of Sydney , Sydney , NSW , Australia
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21
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Hepatic Issues and Complications Associated With Inflammatory Bowel Disease: A Clinical Report From the NASPGHAN Inflammatory Bowel Disease and Hepatology Committees. J Pediatr Gastroenterol Nutr 2017; 64:639-652. [PMID: 27984347 DOI: 10.1097/mpg.0000000000001492] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatobiliary disorders are common in patients with inflammatory bowel disease (IBD), and persistent abnormal liver function tests are found in approximately 20% to 30% of individuals with IBD. In most cases, the cause of these elevations will fall into 1 of 3 main categories. They can be as a result of extraintestinal manifestations of the disease process, related to medication toxicity, or the result of an underlying primary hepatic disorder unrelated to IBD. This latter possibility is beyond the scope of this review article, but does need to be considered in anyone with elevated liver function tests. This review is provided as a clinical summary of some of the major hepatic issues that may occur in patients with IBD.
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22
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Liu K, Wang R, Kariyawasam V, Wells M, Strasser SI, McCaughan G, Corte C, Leong RW. Epidemiology and outcomes of primary sclerosing cholangitis with and without inflammatory bowel disease in an Australian cohort. Liver Int 2017; 37:442-448. [PMID: 27891750 DOI: 10.1111/liv.13328] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 11/18/2016] [Indexed: 12/14/2022]
Abstract
BACKGROUND & AIMS Epidemiological data on primary sclerosing cholangitis (PSC) outside the Northern hemisphere are limited. Similarly, the impact of inflammatory bowel disease (IBD) on PSC outcomes remains unclear. We aimed to study the epidemiology and outcomes of PSC patients with and without IBD in an Australian cohort. METHODS We retrospectively studied PSC patients attending two tertiary referral hospitals over 20 years. Diagnosis of PSC was made according to international guidelines by positive cholangiography and/or liver biopsy (for small duct PSC) with supporting clinical and laboratory evidence. RESULTS Of 208 PSC patients (61% male) were studied (2271patient-years follow-up). The median age of PSC diagnosis was similar for PSC-IBD and PSC-only patients (40 years vs 42 years, P = .35). All 33 deaths occurred in PSC-IBD patients while there were no deaths in PSC-only patients (21% vs 0%, P < .01). However, there were no significant differences in liver transplantation (PSC-only 25% vs PSC-IBD 31%, P = .45) and transplant-free survival between PSC-only and PSC-IBD patients (P = .43). On multivariate Cox regression, only elevated international normalized ratio (INR) was associated with a greater risk of death or liver transplant (HR 2.0, 95% CI 1.1-3.6, P = .02). Development of gastrointestinal malignancy was higher in the PSC-IBD group compared to PSC-only group (22% vs 2%, P < .01). CONCLUSION Australian PSC patients have similar characteristics compared to European and North American cohorts. IBD is a significant predictor of gastrointestinal malignancies. Deaths were more common in PSC-IBD but overall transplant-free survival remained similar in PSC-IBD and PSC-only groups. An elevated INR was an independent predictor of death or liver transplantation.
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Affiliation(s)
- Ken Liu
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Ruoxi Wang
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
| | - Viraj Kariyawasam
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Mark Wells
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Simone I Strasser
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Geoff McCaughan
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Centenary Institute, University of Sydney, Sydney, NSW, Australia
| | - Crispin Corte
- Sydney Medical School, The University of Sydney, Sydney, NSW, Australia
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, NSW, Australia
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23
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Conway G, Velonias G, Andrews E, Garber JJ, Yajnik V, Ananthakrishnan AN. The impact of co-existing immune-mediated diseases on phenotype and outcomes in inflammatory bowel diseases. Aliment Pharmacol Ther 2017; 45:814-823. [PMID: 28105709 PMCID: PMC5315585 DOI: 10.1111/apt.13940] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 11/28/2016] [Accepted: 12/21/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Inflammatory bowel diseases lead to progressive bowel damage and need for surgery. While the increase in prevalence of other immune-mediated diseases in IBD is well recognised, the impact of this on the natural history of IBD is unknown. AIM To determine the impact of concomitant immune-mediated diseases on phenotypes and outcomes in IBD. METHODS Patients with IBD enrolled in a prospective registry were queried about the presence of other immune-mediated diseases, defined as those where immune dysregulation plays a role in pathogenesis. Demographics and disease-related information were obtained. Subjects also completed measures of quality of life. Multivariable regression models compared disease phenotype and outcomes of IBD patients with and without other immune-mediated diseases. RESULTS The cohort included 2145 IBD patients among whom 458 (21%) had another immune-mediated disease. There was no difference in CD phenotype between the two groups. UC patients were more likely to have pancolitis in the presence of another immune-mediated disease (62%) compared to those without (52%, P = 0.02). IBD patients with another immune-mediated disease had higher rates of needing anti-TNF biologics [Odds ratio (OR) 1.31, 95% CI 1.05-1.63] and surgery (OR 1.26, 95% CI 0.99-1.61). The presence of another immune-mediated disease was also associated with lower disease-specific and general physical quality of life. CONCLUSIONS The presence of another immune-mediated disease in IBD patients was associated with higher likelihood of pancolonic involvement in UC, and a modest increase in need for IBD-related surgery and anti-TNF biological therapy. Such patients also experienced worse quality of life.
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Affiliation(s)
- Grace Conway
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Gabriella Velonias
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Elizabeth Andrews
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - John J Garber
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA,Harvard Medical School
| | - Vijay Yajnik
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA,Harvard Medical School
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24
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Lee H, Westerhoff M, Shen B, Liu X. Clinical Aspects of Idiopathic Inflammatory Bowel Disease: A Review for Pathologists. Arch Pathol Lab Med 2017; 140:413-28. [PMID: 27128299 DOI: 10.5858/arpa.2015-0305-ra] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
CONTEXT -Idiopathic inflammatory bowel disease manifests with different clinical phenotypes showing varying behavior and risk for neoplasia. The clinical questions that are posed to pathologists differ depending on phase of the disease and the clinical circumstances. Understanding the clinical aspects of the dynamic disease process will enhance the role of pathology in optimizing the care of patients with inflammatory bowel disease. OBJECTIVE -To review clinical and surgical aspects of inflammatory bowel disease that are relevant to practicing pathologists. DATA SOURCES -The literature was reviewed. CONCLUSIONS -Diagnosis and management of inflammatory bowel disease require an integrated evaluation of clinical, endoscopic, radiologic, and pathologic features. Therefore, close interaction between clinicians and pathologists is crucial. Having this team approach improves understanding of the pertinent clinical and surgical aspects of the disease and assists in the recognition of unusual presentation of variants, as well as mimics of idiopathic inflammatory bowel disease, by pathologists.
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Affiliation(s)
| | | | | | - Xiuli Liu
- From the Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, New York (Dr Lee); the Department of Anatomic Pathology, University of Washington Medical Center, Seattle (Dr Westerhoff); and the Department of Gastroenterology/Hepatology, Digestive Disease Institute (Dr Shen), and the Department of Pathology, Immunology, and Laboratory Medicine (Dr Liu), University of Florida, Gainesville
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Torres J, Caprioli F, Katsanos KH, Lobatón T, Micic D, Zerôncio M, Van Assche G, Lee JC, Lindsay JO, Rubin DT, Panaccione R, Colombel JF. Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases. J Crohns Colitis 2016; 10:1385-1394. [PMID: 27282402 PMCID: PMC5174730 DOI: 10.1093/ecco-jcc/jjw116] [Citation(s) in RCA: 97] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 04/29/2016] [Accepted: 05/26/2016] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course. METHODS As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. RESULTS Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. CONCLUSIONS Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient.
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Affiliation(s)
- Joana Torres
- Surgical Department, Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Flavio Caprioli
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano and Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano, Milan, Italy
| | - Konstantinos H Katsanos
- Division of Gastroenterology, Department of Internal Medicine, School of Medical Sciences, University of Ioannina, Ioannina, Greece
| | - Triana Lobatón
- Department of Gastroenterology, Germans Trias i Pujol University Hospital, Badalona, Barcelona, Spain
| | - Dejan Micic
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
- Barts Health NHS Trust, Royal London Hospital, Whitechapel, London, UK
| | - Marco Zerôncio
- Inflammatory Bowel Disease Unit, Potiguar University School of Medicine, Natal, Brazil
| | - Gert Van Assche
- Division of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - James C Lee
- Department of Medicine, University of Cambridge, Cambridge, UK
| | - James O Lindsay
- Barts Health NHS Trust, Royal London Hospital, Whitechapel, London, UK
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center, Chicago, IL, USA
- Barts Health NHS Trust, Royal London Hospital, Whitechapel, London, UK
| | - Remo Panaccione
- Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada
| | - Jean-Frédéric Colombel
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Fascì-Spurio F, Pavlidis P, Bjarnason I. A new form of chronic inflammatory bowel disease associated with chronic liver disease. Scand J Gastroenterol 2016; 51:644-5. [PMID: 26728083 DOI: 10.3109/00365521.2015.1128141] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
| | - Polychronis Pavlidis
- b Department of Colorectal Surgery and Gastroenterology , King's College Hospital , London , UK
| | - Ingvar Bjarnason
- b Department of Colorectal Surgery and Gastroenterology , King's College Hospital , London , UK
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Clinical Features and Risk Factors of Autoimmune Liver Involvement in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2016; 63:259-64. [PMID: 26756875 DOI: 10.1097/mpg.0000000000001078] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Autoimmune liver disease is reported in up to 7.8% of children with inflammatory bowel disease. A distinct inflammatory bowel disease phenotype has been suggested in adults and in small pediatric cohorts. The aim of the study was to evaluate the features of inflammatory bowel disease associated with autoimmune liver diseases and to analyze the characteristics of the liver disease. METHODS Information on patients was obtained from the Italian Pediatric Inflammatory Bowel Disease Registry. Data of patients with and without autoimmune liver disease were compared. RESULTS Autoimmune liver disease was detected in 6.8% of the 677 patients enrolled and was significantly associated with the diagnosis of ulcerative colitis (83%), with pancolonic involvement (84%), and with perinuclear antineutrophil cytoplasmic antibody positivity (41%) (all Ps < 0.05). Autoimmune liver disease was defined as sclerosing cholangitis in 61% of the patients and as an overlap syndrome in 33%. Concomitant intra- and extrahepatic biliary involvement was reported in 61% of cases, whereas exclusive extrahepatic lesions were reported in 21%. Hepatobiliary complications were observed in 9% of the patients during follow-up. CONCLUSIONS Autoimmune liver disease, especially sclerosing cholangitis, was significantly more common in patients with extensive ulcerative colitis. Although complications are relatively rare in the pediatric age, monitoring is recommended.
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Torres J, Bao X, Goel A, Colombel JF, Pekow J, Jabri B, Williams K, Castillo A, Odin J, Meckel K, Fasihuddin F, Peter I, Itzkowitz S, Hu J. The features of mucosa-associated microbiota in primary sclerosing cholangitis. Aliment Pharmacol Ther 2016; 43:790-801. [PMID: 26857969 PMCID: PMC5177987 DOI: 10.1111/apt.13552] [Citation(s) in RCA: 113] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Revised: 11/12/2015] [Accepted: 01/18/2016] [Indexed: 12/12/2022]
Abstract
BACKGROUND Little is known about the role of the microbiome in primary sclerosing cholangitis. AIM To explore the mucosa-associated microbiota in primary sclerosing cholangitis (PSC) patients across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)-only patients and healthy controls. METHODS Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies. RESULTS Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order. CONCLUSIONS The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order.
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Affiliation(s)
- Joana Torres
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Xiuliang Bao
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA,Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Aparna Goel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Jean-Frederic Colombel
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Joel Pekow
- Section of Gastroenterology, Hepatology, and Nutrition University of Chicago, Chicago, Illinois, USA
| | - Bana Jabri
- Section of Gastroenterology, Hepatology, and Nutrition University of Chicago, Chicago, Illinois, USA
| | - Kelli Williams
- Section of Gastroenterology, Hepatology, and Nutrition University of Chicago, Chicago, Illinois, USA
| | - Anabella Castillo
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Joseph Odin
- Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Katherine Meckel
- Section of Gastroenterology, Hepatology, and Nutrition University of Chicago, Chicago, Illinois, USA
| | - Farah Fasihuddin
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Inga Peter
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Steven Itzkowitz
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Jianzhong Hu
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, USA
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Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that most often occurs in association with inflammatory bowel disease (IBD). We examined whether the activity or colonic distribution of IBD differed in pediatric patients with and without PSC. METHODS We compared colonic disease distribution, physician global assessment scores, Mayo endoscopic severity scores, IBD-related hospital admissions, and colonic resection surgery rate in a retrospective cohort of pediatric patients with IBD with and without PSC. RESULTS We identified 37 patients with PSC-IBD, and 137 non-PSC matched IBD controls. Pancolitis was seen in 89.7 versus 72.4% (P = 0.051) of patients with PSC-IBD and rectal sparing in 24.3 versus 21.6% (P = 0.721) of patients with IBD. Physician global assessment and Mayo scores at presentation and in follow-up were similar in PSC-IBD and IBD. Patients with PSC-IBD had 0.19 admissions per person-year compared with 0.25 in patients with IBD. The incidence rate ratio for admission was 0.75 (95% confidence interval (CI), 0.51-1.08). The 5-year probability of colonic surgery was 16.4% (95% CI, 7.0-36.0) in patients with PSC-IBD and 24.7% (95% CI, 17.7-33.8) in patients with IBD (P = 0.271). In a multivariate model, male sex (hazard ratio [HR] = 2.2 [95% CI, 1.1-4.3]) and the presence of a non-PSC immune-mediated comorbidity {HR = 3.9 (95% CI, 1.5-10.4), but not PSC (HR = 0.5 [95% CI, 0.2-1.3])} or Crohn's disease (HR = 0.5 [95% CI, 0.1-1.5]), were risk factors for colonic surgery in pediatric IBD. CONCLUSIONS Patients with IBD and PSC were more likely to present with pancolitis, but had similar rates of rectal sparing. Patients with IBD showed similar disease activity across a wide range of measures, at presentation and in follow-up, regardless of the presence of PSC.
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Bjarnason I, Hayee B, Pavlidis P, Kvasnovsky C, Scalori A, Sisson G, Charlesworth A, Shaikh H, Bjornsson E, Heneghan MA. Contrasting Pattern of Chronic Inflammatory Bowel Disease in Primary and Autoimmune Sclerosing Cholangitis. EBioMedicine 2015; 2:1523-7. [PMID: 26629548 PMCID: PMC4634318 DOI: 10.1016/j.ebiom.2015.08.041] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Revised: 08/29/2015] [Accepted: 08/29/2015] [Indexed: 12/22/2022] Open
Abstract
Background Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (AISC) are related, but distinct chronic liver diseases. PSC is associated with a high prevalence of ulcerative colitis while the intestinal inflammation associated with AISC is less well characterised. Aims To assess and contrast aspects of intestinal inflammation in patients with AISC and PSC and compare the clinical features with those of patients with ulcerative colitis and Crohn's disease. Methods 23 and 22 patients with AISC and PSC, respectively, underwent review of colonoscopy and biopsy findings, capsule enteroscopy and assessment of clinical and inflammatory (faecal calprotectin) disease activity, which was compared with that of patients with ulcerative colitis and Crohn's disease (n = 55 each). Findings Five and 6 patients with AISC and PSC, respectively, had normal colonoscopy and faecal calprotectin levels of 34.4 ± 8.3 and 39.7 ± 8.4 μg/g, respectively (normal < 50 μg/g), whereas 18 and 16, respectively, had identical variably severe, right sided colitis with frequent rectal sparing, consistent with ulcerative colitis. Mean (± SD) faecal calprotectin levels did not differ significantly (p > 0.05) between patients with intestinal inflammation in AISC (588 ± 549 μg/g), PSC (421 ± 351 μg/g), ulcerative colitis (501 ± 656 μg/g) or Crohn's disease (476 ± 571 μg/g). Capsule enteroscopy showed that 7 of 18 (39%) (p < 0.03) of those with AISC had small bowel mucosal breaks whereas no patient with PSC had these findings. Interpretation Collectively these findings lend support to the suggestion that the chronic inflammatory bowel disease associated with PSC and in particular AISC may represent a distinct nosologic entity different from classic ulcerative colitis and Crohn's disease.
The ulcerative colitis (UC) associated with autoimmune and primary sclerosing cholangitis behaves differently to classic UC. Patients with autoimmune and primary sclerosing cholangitis have similar pattern of colitis, resembling ulcerative colitis. 39% of those with autoimmune sclerosing cholangitis had small intestinal mucosal breaks resembling Crohn’s disease. The colitis associated with these chronic liver diseases differs distinctively from classic inflammatory bowel disease. Most patients with the chronic liver disease primary sclerosing cholangitis have a colitis, which is classified as ulcerative colitis. Here we show that patients with a related liver disease, namely autoimmune sclerosing cholangitis, have an identical colitis, but 39% also have small bowel erosions or ulcers which is more suggestive of Crohn's disease. Intestinal inflammatory activity was similar in these patients as compared with patients with ulcerative colitis and Crohn's disease. Collectively these findings and the contrasting natural history of the colitis of chronic liver suggests that this represents a separate nosologic entity from classic inflammatory bowel disease.
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Affiliation(s)
- Ingvar Bjarnason
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK ; Department of Minimally Invasive Colorectal Surgery, King's College Hospital, Denmark Hill, London, UK
| | - Bu Hayee
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK
| | - Polychronis Pavlidis
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK
| | - Charlotte Kvasnovsky
- Department of Minimally Invasive Colorectal Surgery, King's College Hospital, Denmark Hill, London, UK
| | - Astrid Scalori
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London, UK
| | - Guy Sisson
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK
| | - Annika Charlesworth
- Department of Gastroenterology, King's College Hospital, Denmark Hill, London, UK
| | - Hizbullah Shaikh
- Department of Histopathology, King's College Hospital, Denmark Hill, London, UK
| | - Einar Bjornsson
- Department of Gastroenterology, Landspitali University Hospital, Reykjavik, Iceland
| | - Michael A Heneghan
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London, UK
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Dohan A, Faraoun S, Barral M, Guerrache Y, Boudiaf M, Dray X, Hoeffel C, Allez M, Farges O, Beaugerie L, Aparicio T, Marteau P, Fishman E, Lucidarme O, Eveno C, Pocard M, Dautry R, Soyer P. Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features. Diagn Interv Imaging 2015; 96:871-83. [DOI: 10.1016/j.diii.2015.02.009] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 02/24/2015] [Indexed: 12/11/2022]
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Solid Organ Transplantation in Patients with Inflammatory Bowel Diseases (IBD): Analysis of Transplantation Outcome and IBD Activity in a Large Single Center Cohort. PLoS One 2015; 10:e0135807. [PMID: 26288187 PMCID: PMC4545391 DOI: 10.1371/journal.pone.0135807] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Accepted: 07/27/2015] [Indexed: 12/12/2022] Open
Abstract
Background Currently, limited data of the outcome of inflammatory bowel disease (IBD) in patients after solid organ transplantation (SOT) are available. We aimed to analyze effects of SOT on the IBD course in a large IBD patient cohort. Methods Clinical data from 1537 IBD patients were analyzed for patients who underwent SOT (n = 31) between July 2002 and May 2014. Sub-analyses included SOT outcome parameters, IBD activity before and after SOT, and efficacy of IBD treatment. Results 4.74% of patients with ulcerative colitis (UC) and 0.84% of patients with Crohn’s disease (CD) underwent SOT (p = 2.69 x 10−6, UC vs. CD). 77.4% of patients with SOT underwent liver transplantation (LTx) with tacrolimus-based immunosuppressive therapy after SOT. All LTx were due to primary sclerosing cholangitis (PSC) or PSC overlap syndromes. Six patients (19.4%) required renal transplantation and one patient (3.2%) heart transplantation. A survival rate of 83.9% after a median follow-up period of 103 months was observed. Before SOT, 65.0% of patients were in clinical remission and 5 patients received immunosuppressive therapy (16.1%). After SOT, 61.0% of patients were in remission (p = 1.00 vs. before SOT) and 29.0% required IBD-specific immunosuppressive or anti-TNF therapy (p = 0.54 vs. before SOT). 42.9% of patients with worsening of IBD after SOT were at higher risk of needing steroid therapy for increased IBD activity (p = 0.03; relative risk (RR): 10.29; 95% CI 1.26–84.06). Four patients (13.0%) needed anti-TNF therapy after SOT (response rate 75%). Conclusions SOT was more common in UC patients due to the higher prevalence of PSC-related liver cirrhosis in UC. Despite mainly tacrolimus-based immunosuppressive regimens, outcome of SOT and IBD was excellent in this cohort. In this SOT cohort, concomitant immunosuppressive therapy due to IBD was well tolerated.
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Parian A, Lazarev M. Who and how to screen for cancer in at-risk inflammatory bowel disease patients. Expert Rev Gastroenterol Hepatol 2015; 9:731-46. [PMID: 25592672 DOI: 10.1586/17474124.2015.1003208] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Inflammatory bowel diseases (IBDs) include both Crohn's disease and ulcerative colitis and both diseases are marked by inflammation within the gastrointestinal tract. Due to long-standing inflammation, IBD patients are at increased risk of colorectal cancer, especially patients with chronic inflammation, pancolitis, co-diagnosis of primary sclerosing cholangitis and a longer duration of disease. Small bowel inflammation places Crohn's patients at an increased risk of small bowel cancer. A higher risk of skin cancers, lymphomas and cervical abnormalities is also seen in IBD patients; this is likely related to both disease factors and the presence of immunosuppressive medication. This article reviews which patients are at an increased risk of IBD-associated or IBD treatment-associated cancers, when to begin screening and which screening methods are recommended.
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Affiliation(s)
- Alyssa Parian
- Department of Gastroenterology, Johns Hopkins University, 4940 Eastern Avenue, Building A, Baltimore, MD 21224, USA
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Raszeja-Wyszomirska J, Kucharski R, Zygmunt M, Safranow K, Miazgowski T. The impact of fragility fractures on health-related quality of life in patients with primary sclerosing cholangitis. HEPATITIS MONTHLY 2015; 15:e25539. [PMID: 25972904 PMCID: PMC4426354 DOI: 10.5812/hepatmon.25539] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/22/2014] [Revised: 01/23/2015] [Accepted: 02/04/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Osteoporosis occurs frequently in patients with chronic cholestatic liver diseases, yet data are scarce regarding the prevalence of osteoporosis and fragility fractures and their impact on Health-Related Quality of Life (HRQoL) in Primary Sclerosing Cholangitis (PSC). OBJECTIVES We aimed to assess Bone Mineral Density (BMD), physical activity and incidence of fragility fractures in patients with PSC. We also sought associations between prior fractures and HRQoL. PATIENTS AND METHODS The study was performed on 33 patients (11 females, 22 males) aged 35.3 ± 13 years. HRQoL was assessed by Short Form (SF)-36, Primary Biliary Cirrhosis (PBC)-40 and PBC-27 questionnaires. BMD was measured by densitometry in the lumbar spine and hip. Physical activity was assessed by questionnaire. RESULTS In 32% of patients, BMD measured in the hip or spine was below 1.0 Standard Deviation. A history of fragility fractures (distal forearm and ribs) was reported in six patients (18%). In SF-36 assessment, patients with fractures had lower scores in the role functioning, general health and vitality domains and Physical Component Summary (PCS) than those without fractures. Prior fractures adjusted for gender and PSC duration were associated with lower PCS and Mental Component Summary (MCS) scores. Symptoms and fatigue (assessed by PBC) and prior fractures were inversely associated with MCS (P = 0.007). CONCLUSIONS In middle-aged subjects with PSC, we found a high rate of non-vertebral fractures and a moderately decreased BMD in lumbar spine and hip. Fragility fractures had an impact on physical and mental aspects of HRQoL.
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Affiliation(s)
- Joanna Raszeja-Wyszomirska
- Hepatology and Internal Medicine Unit, Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Robert Kucharski
- Liver Research Laboratories, Pomeranian Medical University, Szczecin, Poland
| | - Marta Zygmunt
- Hepatology and Internal Medicine Unit, Department of General Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland
| | - Krzysztof Safranow
- Department of Biochemistry and Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Tomasz Miazgowski
- Department of Hypertension and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
- Corresponding Author: Tomasz Miazgowski, Department of Hypertension and Internal Medicine, Pomeranian Medical University, Szczecin, Poland. Tel: +48-91425 3550, Fax: +48-914253552, E-mail:
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Reinisch W, Reinink AR, Higgins PDR. Factors associated with poor outcomes in adults with newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol 2015; 13:635-42. [PMID: 24887059 DOI: 10.1016/j.cgh.2014.03.037] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2013] [Revised: 03/05/2014] [Accepted: 03/21/2014] [Indexed: 02/07/2023]
Abstract
It is a challenge to accurately identify patients with early stage ulcerative colitis (UC) who are at highest risk for a poor outcome and therefore might require salvage therapy. Several epidemiologic and clinical studies have analyzed factors associated with poor prognosis and increased risk for colectomy. We review prognostic factors for adults with newly diagnosed UC and discuss which patients might benefit from rapid and progressive therapy. Patients with poor prognoses tend to be young nonsmokers with high levels of inflammatory biomarkers, low levels of hemoglobin, and extensive disease, based on colonoscopy. We examine these risk factors in 2 hypothetical patients who have been newly diagnosed with UC.
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Affiliation(s)
- Walter Reinisch
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
| | - Andrew R Reinink
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
| | - Peter D R Higgins
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan
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Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. J Clin Transl Hepatol 2014; 2:266-84. [PMID: 26357630 PMCID: PMC4521232 DOI: 10.14218/jcth.2014.00024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 10/15/2014] [Accepted: 10/19/2014] [Indexed: 12/12/2022] Open
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease.
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Affiliation(s)
- Renée M. Marchioni Beery
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Renée M. Marchioni Beery, DO, Division of Internal Medicine, Department of Gastroenterology and Hepatology, 263 Farmington Avenue, Farmington, CT 06030-1845, USA. Tel: +01-860-679-3158, Fax: +01-860-679-3159. E-mail:
| | - Haleh Vaziri
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Faripour Forouhar
- Department of Pathology and Lab Medicine, University of Connecticut Health Center, Farmington, CT, USA
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Gizard E, Ford AC, Bronowicki JP, Peyrin-Biroulet L. Systematic review: The epidemiology of the hepatobiliary manifestations in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2014; 40:3-15. [PMID: 24815622 DOI: 10.1111/apt.12794] [Citation(s) in RCA: 95] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2013] [Revised: 12/31/2013] [Accepted: 04/22/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND Extraintestinal manifestations are frequent in inflammatory bowel diseases (IBD). Most studies published so far focused on viral hepatitis and liver toxicity of IBD-related drugs. AIM To conduct a systematic review of hepatobiliary manifestations associated with IBD. We excluded viral hepatitis and liver toxicity of IBD-related drugs. METHODS Studies were identified through the electronic database of MEDLINE, EMBASE and the annual meetings of Digestive Disease Week, the American College of Gastroenterology, the United European Gastroenterology Week and the European Crohn's and Colitis Organization. RESULTS One hundred and forty six articles were included in this systematic review. Cholelithiasis is more frequent in Crohn's disease (CD) than in general population. Prevalence of cholelithiasis in CD ranged from 11% to 34%, whereas it ranges from 5.5% to 15% in non-IBD patients. PSC is more frequent in UC than in CD. Prevalence of PSC ranges from 0.76% to 5.4% in UC and from 1.2% to 3.4% in CD. There is a male predominance when PSC is associated with UC, with a male/female ratio ranging from 65/35 to 70/30. No conclusion can be made on a possible increased risk of gall-bladder carcinoma. Mean prevalence of fatty liver is 23% (range, 1.5-55%). Hepatic amyloidosis occurs in less than 1% of IBD. Liver abscess is encountered mainly in CD. Portal vein thrombosis occurs in 39% to 45% of IBD patients undergoing proctocolectomy. CONCLUSIONS Hepatobiliary manifestations associated with inflammatory bowel diseases are frequent and probably underdiagnosed.
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Affiliation(s)
- E Gizard
- Inserm U954 and Department of Hepato-Gastroenterology, University Hospital of Nancy-Brabois, Université de Lorraine, Vandoeuvre-lès-Nancy, France
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Abstract
The interaction between inflammatory bowel disease (IBD) and hepatobiliary manifestations represents a classic example of liver-gut crosstalk. The importance of liver-gut crosstalk in IBD is demonstrated in the pathogenesis and outcome of primary sclerosing cholangitis (PSC) in IBD patients. Immunoglobulin G4-associated cholangitis (IAC), which has recently been described in UC patients, may also illustrate the significance of gut-liver interaction in these patients. Presence of these hepatobiliary manifestations influences the outcome of associated IBD, in particular ulcerative colitis (UC), and vice versa. The pathogenesis of PSC is postulated to be related to gut inflammation in IBD that results in inflammation in the portal tracts (the 'leaky gut'). Enterohepatic circulation of lymphocytes from the gut to the liver is also of potential relevance to PSC pathogenesis and outcomes. The presence of PSC and gut inflammation in IBD influences the course and outcomes of both diseases. Further research is required, to understand the mutual effect of liver-gut crosstalk in the outcomes of UC patients, and highlights the importance of an interdisciplinary approach-involving gastroenterologists, hepatologists, advanced endoscopists and liver transplant surgeons-in the management of these patients.
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Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology/Hepatology, Digestive Disease Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
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Tsaitas C, Semertzidou A, Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol 2014; 6:178-187. [PMID: 24799986 PMCID: PMC4009473 DOI: 10.4254/wjh.v6.i4.178] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 03/05/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with primary sclerosing cholangitis (PSC) complicated by inflammatory bowel disease (IBD) represent a distinct subset of patients with unique characteristics, which have serious clinical implications. The aim of this literature review was to shed light to the obscure clinical and molecular aspects of the two diseases combined utilizing current data available and putting issues of diagnosis and treatment into perspective. The prevalence of IBD, mainly ulcerative colitis in PSC patients is estimated to be 21%-80%, dependent on screening programs and nationality. PSC-associated colitis is likely to be extensive, characterized by rectal sparing, backwash ileitis, and generally mild symptoms. It is also more likely to progress to colorectal malignancy, making it imperative for clinicians to maintain a high level of suspicion when tackling PSC patients. There is no optimal surveillance strategy but current guidelines advocate that colonoscopy is necessary at the time of PSC diagnosis with annual endoscopic follow-up. Random biopsies have been criticized and a shift towards targeted biopsies using chromoendoscopy, laser endomicroscopy and narrow-band imaging has been noted. Techniques directed towards genetic mutations instead of histological abnormalities hold promise for easier, more accurate diagnosis of dysplastic lesions. Chemopreventive measures against colorectal cancer have been sought in these patients. Ursodeoxycholic acid seemed promising at first but subsequent studies yielded conflicting results showing anticarcinogenic effects in low doses (8-15 mg/kg per day) and carcinogenic properties in high doses (15-30 mg/kg per day).
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Affiliation(s)
- Christos Tsaitas
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
| | - Anysia Semertzidou
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
| | - Emmanouil Sinakos
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
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Karlsen TH, Vesterhus M, Boberg KM. Review article: controversies in the management of primary biliary cirrhosis and primary sclerosing cholangitis. Aliment Pharmacol Ther 2014; 39:282-301. [PMID: 24372568 DOI: 10.1111/apt.12581] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 10/09/2013] [Accepted: 11/18/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Despite considerable advances over the last two decades in the molecular understanding of cholestasis and cholestatic liver disease, little improvement has been made in diagnostic tools and therapeutic strategies. AIMS To critically review controversial aspects of the scientific basis for common clinical practice in primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) and to discuss key ongoing challenges to improve patient management. METHODS We performed a literature search using PubMed and by examining the reference lists of relevant review articles related to the clinical management of PBC and PSC. Articles were considered on the background of the European Association for the Study of the Liver (EASL) and the American Association for the Study of Liver Diseases (AASLD) practice guidelines and clinical experience of the authors. RESULTS Ongoing challenges in PBC mainly pertain to the improvement of medical therapy, particularly for patients with a suboptimal response to ursodeoxycholic acid. In PSC, development of medical therapies and sensitive screening protocols for cholangiocarcinoma represent areas of intense research. To rationally improve patient management, a better understanding of pathogenesis, including complications like pruritis and fatigue, is needed and there is a need to identify biomarker end-points for treatment effect and prognosis. Timing of liver transplantation and determining optimal regimens of immunosuppression post-liver transplantation will also benefit from better appreciation of pre-transplant disease mechanisms. CONCLUSION Controversies in the management of PBC and PSC relate to topics where evidence for current practice is weak and further research is needed.
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Affiliation(s)
- T H Karlsen
- Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway
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Xavier JCC, Coelho KIR, Sassaki LY, Yamashiro FDS, Oliveira KCL, Rodrigues MAM. Primary sclerosing cholangitis associated with severe ulcerative colitis in a young man. AUTOPSY AND CASE REPORTS 2013; 3:37-41. [PMID: 28584805 PMCID: PMC5453659 DOI: 10.4322/acr.2013.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2013] [Accepted: 12/03/2013] [Indexed: 11/23/2022] Open
Abstract
Primary sclerosing cholangitis, a chronic progressive cholestatic liver disease, is the most serious hepatobiliary complication of ulcerative colitis (UC). The authors present the case of a severe and intractable form of UC associated with primary sclerosing cholangitis, in which the diagnosis of this hepatobiliary complication was made during the postmortem examination. A 19-year-old man, with an 8-month diagnosis of UC, was non-responsive to any therapeutic approach. He presented at the emergency care unit severely ill and with cachexia, and subsequently died of septic shock. The postmortem examination confirmed the clinical diagnosis of severe UC and disclosed the presence of primary sclerosing cholangitis. Although laboratory tests have shown a typical cholestatic profile with elevated alkaline phosphatase and gamma-glutamyl transferase levels, hepatic dysfunction was related to sepsis. This report highlights how challenging the diagnosis of primary sclerosing cholangitis can be and shows the value of the postmortem examination to add important information to a medical diagnosis.
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Affiliation(s)
| | | | - Ligia Yukie Sassaki
- Department of Internal Medicine - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu/SP, Brazil
| | - Fabio da Silva Yamashiro
- Department of Internal Medicine - Faculdade de Medicina - Universidade Estadual Paulista, Botucatu/SP, Brazil
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Rojas-Feria M, Castro M, Suárez E, Ampuero J, Romero-Gómez M. Hepatobiliary manifestations in inflammatory bowel disease: The gut, the drugs and the liver. World J Gastroenterol 2013; 19:7327-7340. [PMID: 24259964 PMCID: PMC3831215 DOI: 10.3748/wjg.v19.i42.7327] [Citation(s) in RCA: 91] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2013] [Revised: 08/07/2013] [Accepted: 09/29/2013] [Indexed: 02/06/2023] Open
Abstract
Abnormal liver biochemical tests are present in up to 30% of patients with inflammatory bowel disease (IBD), and therefore become a diagnostic challenge. Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis (UC), and typically do not correlate with intestinal activity. Primary sclerosing cholangitis (PSC) is the most common hepatobiliary manifestation of IBD, and is more prevalent in UC. Approximately 5% of patients with UC develop PSC, with the prevalence reaching up to 90%. Cholangiocarcinoma and colon cancer risks are increased in these patients. Less common disorders include autoimmune hepatitis/PSC overlap syndrome, IgG4-associated cholangiopathy, primary biliary cirrhosis, hepatic amyloidosis, granulomatous hepatitis, cholelithiasis, portal vein thrombosis, liver abscess, and non-alcoholic fatty liver disease. Hepatitis B reactivation during immunosuppressive therapy is a major concern, with screening and vaccination being recommended in serologically negative cases for patients with IBD. Reactivation prophylaxis with entecavir or tenofovir for 6 to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen (HBsAg) positive, independently from viral load. HBsAg negative and anti-HBc positive patients, with or without anti-HBs, should be closely monitored, measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy, and should be treated if the viral load increases. On the other hand, immunosuppressive therapy does not seem to promote reactivation of hepatitis C, and hepatitis C antiviral treatment does not influence IBD natural history either. Most of the drugs used for IBD treatment may induce hepatotoxicity, although the incidence of serious adverse events is low. Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant. Methotrexate-related hepatotoxicity has been described in 14% of patients with IBD, in a dose-dependent manner. Liver biopsy is not routinely recommended. Biologics-related hepatotoxicity is rare, but has been shown most frequently in patients treated with infliximab. Thiopurines have been associated with veno-occlusive disease, regenerative nodular hyperplasia, and liver peliosis. Routine liver biochemical tests are recommended, especially during the first month of treatment. All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement. Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.
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Abstract
Ulcerative colitis (UC) is a chronic idiopathic inflammatory disease of the gastrointestinal tract that affects the mucosal lining of the colon. Recent epidemiological data show that its incidence and prevalence are increasing in many parts of the world, in parallel with altered lifestyles, improved access to health, improved sanitation and industrialisation rates. Current therapeutic strategies for treating UC have only been moderately successful. Despite major recent advances in inflammatory bowel disease therapeutic resources, a considerable proportion of patients are still refractory to conventional treatment. Less than half of all patients achieve long-term remission, many require colectomy, and the disease still has a major impact on patients' lives. Moreover, recent data point to slightly raised mortality. While these outcomes could be partly improved by optimising current therapeutic strategies, they clearly highlight the need to develop new therapies. Currently, a number of promising and innovative therapeutic approaches are being explored, some of which will hopefully survive to reach the clinic. Until such a time arrives, it is important that a better understanding of the clinical particularities of the disease, an improved knowledge of the host-microbiome negative interactions and of the environmental factors beyond disease development is achieved to obtain the final and desired outcome: to provide better treatment and quality of life for patients with this disabling disease.
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Affiliation(s)
- Joana Torres
- Gastroenterology Service, Surgery Department, Hospital Beatriz Ângelo, , Loures, Portugal
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Jørgensen KK, Lindström L, Cvancarova M, Karlsen TH, Castedal M, Friman S, Schrumpf E, Foss A, Isoniemi H, Nordin A, Holte K, Rasmussen A, Bergquist A, Vatn MH, Boberg KM. Immunosuppression after liver transplantation for primary sclerosing cholangitis influences activity of inflammatory bowel disease. Clin Gastroenterol Hepatol 2013; 11:517-23. [PMID: 23333218 DOI: 10.1016/j.cgh.2012.12.027] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2012] [Revised: 11/04/2012] [Accepted: 12/21/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Previous studies have shown conflicting results regarding the course of inflammatory bowel disease (IBD) after liver transplantation in patients with primary sclerosing cholangitis (PSC). We studied the progression of IBD in patients with PSC who have undergone liver transplantation. We also studied risk factors, including medical therapy, that could influence on IBD disease activity. METHODS In a longitudinal multicenter study, we analyzed data from the Nordic Liver Transplant Group on 439 patients with PSC who underwent liver transplantation from November 1984 through December 2006; 353 had IBD at the time of transplantation. We compared IBD activity before and after liver transplantation. Two hundred eighteen patients who had an intact colon and had undergone pretransplant and post-transplant colonoscopies were characterized further. RESULTS Macroscopic colonic inflammation was more frequent after liver transplantation than before liver transplantation (153 vs 124 patients; P < .001). The degree of inflammation decreased in 37 patients (17%), was unchanged in 93 patients (43%), and increased in 88 patients (40%) (P < .001). The rate of relapse after transplantation was higher than that before transplantation (P < .001), and overall clinical IBD activity also increased (P < .001). Young age at diagnosis of IBD and dual treatment with tacrolimus and mycophenolate mofetil were significant risk factors for increased IBD activity after transplantation, whereas combination treatment with cyclosporin A and azathioprine had protective effects. CONCLUSIONS Immunosuppression affects IBD activity after liver transplantation in patients with PSC; a shift from present standard maintenance treatment of tacrolimus and mycophenolate mofetil to cyclosporin A and azathioprine should be considered for these patients.
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Affiliation(s)
- Kristin Kaasen Jørgensen
- Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
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Chaparro M, Trapero-Marugán M, Guijarro M, López C, Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and primary sclerosing cholangitis: a case report and a short review of the literature. J Crohns Colitis 2013; 7:e61-5. [PMID: 22552273 DOI: 10.1016/j.crohns.2012.04.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Revised: 04/01/2012] [Accepted: 04/03/2012] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis is a chronic progressive disorder which involves the medium size and large ducts in the intrahepatic and extrahepatic biliary tree. The great majority of cases have underlying inflammatory bowel disease, mainly ulcerative colitis. A higher risk of colorectal cancer has been described among ulcerative colitis patients with primary sclerosing cholangitis. Here we report a case of a primary sclerosing cholangitis in a young male with a newly diagnosed ulcerative colitis presenting with colonic dysplasia. Surveillance for colorectal cancer should be strongly recommended in this group of patients.
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Affiliation(s)
- María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Boonstra K, van Erpecum KJ, van Nieuwkerk KMJ, Drenth JPH, Poen AC, Witteman BJM, Tuynman HARE, Beuers U, Ponsioen CY. Primary sclerosing cholangitis is associated with a distinct phenotype of inflammatory bowel disease. Inflamm Bowel Dis 2012; 18:2270-6. [PMID: 22407885 DOI: 10.1002/ibd.22938] [Citation(s) in RCA: 136] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Accepted: 02/14/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD). The aim of this study was to assess the IBD phenotype associated with PSC in a large well-phenotyped population-based PSC cohort using endoscopic and histopathologic criteria. METHODS PSC cases were identified and ascertained, fulfilling well-established criteria, in 39 hospitals in a geographically defined region of The Netherlands. IBD location was recorded according to the Montreal Classification. As this classification does not consider segmental inflammation, backwash ileitis, or rectal sparing, an additional subgroup analysis was performed in 80 cases and 80 age- and sex-matched IBD controls, reviewing all endoscopy and pathology reports filed between 2000 and 2010. RESULTS In all, 380 (66%) of a total of 579 PSC patients had coexistent IBD, mainly ulcerative colitis (UC) (75%). Overall, 207 (83%) of the PSC-UC patients had a pancolitis, 32 (13%) a left-sided colitis, and 9 (4%) a proctitis only. Seventy (95%) PSC-Crohn's disease (CD) patients had an (ileo)colitis and four (5%) ileitis only. In the subgroup analysis 53 (66%) PSC-UC patients were identified, 24 (30%) PSC-CD patients, and three (4%) PSC-IBD-U patients. Fifty (94%) PSC-UC patients had a pancolitis, compared with 32 (62%) matched UC patients (P < 0.001). Left-sided colitis was seen in 16 (31%) UC controls and in one PSC-UC patient (P < 0.001). Backwash ileitis and rectal sparing were rare findings (<10%) in the cohorts under study. CONCLUSIONS IBD in PSC patients represents a distinct phenotype in that pancolitis is observed in 94% of PSC-UC and colitis in 96% of PSC-CD patients. Backwash ileitis and rectal sparing were rare findings in the PSC-UC patients.
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Affiliation(s)
- Kirsten Boonstra
- Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
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Ordonez F, Lacaille F, Canioni D, Talbotec C, Fournet JC, Cerf-Bensussan N, Goulet O, Schmitz J, Ruemmele FM. Pediatric ulcerative colitis associated with autoimmune diseases: a distinct form of inflammatory bowel disease? Inflamm Bowel Dis 2012; 18:1809-17. [PMID: 22238154 DOI: 10.1002/ibd.22864] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2011] [Accepted: 12/05/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND The pathogenesis of inflammatory bowel disease (IBD) is multifactorial, with some patients presenting additional autoimmune symptoms. Inflammatory colitis associated with autoimmune (AI) liver disease appears to have clinical features different from those of "classical" ulcerative colitis (CUC). The aim of this study was to describe these features, in order to differentiate a subgroup of colitis associated with autoimmunity (CAI) from CUC. METHODS Twenty-eight consecutive children with inflammatory colitis associated with primary sclerosing cholangitis (PSC), celiac disease, or AI hepatitis were compared with a matched control group of 27 children with isolated UC. Clinical course, histology, as well as inflammatory profile in the colonic mucosa based on real-time polymerase chain reaction (PCR) were analyzed. RESULTS In CAI the main digestive symptoms at disease onset were abdominal pain (12/28) and bloody strings in the stool (12/28), along with a high prevalence of autoimmune diseases in relatives, as compared with bloody diarrhea in the CUC group (26/27). At diagnosis, pancolitis was seen in 18/28 CAI patients compared with 8/27 in UC. In CAI, the pathological findings were different from CUC: 1) major lesions predominantly located in the right colon; 2) pseudo-villous appearance of the mucosa, and strong infiltration with eosinophils; 3) mild glandular lesions; and 4) differing inflammatory infiltrate with reduced FOXP3, interleukin (IL)-2, and thymic stromal lymphopoietin (TSLP) levels. Evolution in CAI was less aggressive, requiring less corticosteroids/immunomodulators. CONCLUSIONS Precise clinical, histological, and molecular analyses reveal marked differences between patients with CUC and those with associated AI phenomena, supporting the hypothesis of a distinct AI presentation of IBD.
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Affiliation(s)
- Felipe Ordonez
- Assistance Publique-Hôpitaux de Paris, Hôpital Necker-Enfants Malades, Service de Gastroentérologie pédiatrique, Paris, France
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Dyson JK, Rutter MD. Colorectal cancer in inflammatory bowel disease: What is the real magnitude of the risk? World J Gastroenterol 2012; 18:3839-48. [PMID: 22876036 PMCID: PMC3413056 DOI: 10.3748/wjg.v18.i29.3839] [Citation(s) in RCA: 158] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Revised: 05/22/2012] [Accepted: 05/26/2012] [Indexed: 02/06/2023] Open
Abstract
The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in IBD. IBD-associated CRC (IBD-CRC) affects patients at a younger age than sporadic CRC. The prognosis for sporadic CRC and IBD-CRC is similar, with a 5-year survival of approximately 50%. Identifying at risk patients and implementing appropriate surveillance for these patients is central to managing the CRC risk in IBD. The increased risk of colorectal cancer in association with IBD is thought to be due to genetic and acquired factors. The link between inflammation and cancer is well recognised but the molecular biology, immune pathobiology and genetics of IBD-CRC are areas of much ongoing research. This review examines the literature relating to IBD-CRC, focusing on the incidence of IBD-CRC and examining potential risk factors including age at diagnosis, gender, duration and extent of colitis, severity of inflammation, family history of sporadic CRC and co-existent primary sclerosing cholangitis (PSC). Confirmed risk factors for IBD-CRC are duration, severity and extent of colitis, the presence of co-existent PSC and a family history of CRC. There is insufficient evidence currently to support an increased frequency of surveillance for patients diagnosed with IBD at a younger age. Evidence-based guidelines advise surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis, with the interval for further surveillance guided by risk factors (extent of disease, family history of CRC, post-inflammatory polyps, concomitant PSC, personal history of colonic dysplasia, colonic strictures). There is a move away from using random colonic biopsies towards targeted biopsies aimed at abnormal areas identified by newer colonoscopic techniques (narrow band imaging, chromoendoscopy, confocal microendoscopy).
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Blonski W, Buchner AM, Lichtenstein GR. Clinical predictors of aggressive/disabling disease: ulcerative colitis and crohn disease. Gastroenterol Clin North Am 2012; 41:443-62. [PMID: 22500528 DOI: 10.1016/j.gtc.2012.01.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Many clinical factors predict the aggressive course of CD. Younger age at initial diagnosis, the presence of perianal lesions, ileal involvement, smoking, and the need for therapy with corticosteroids are the major predictors of disabling disease or change of behavior to a more aggressive disease. On the other hand, treatment with azathioprine and biologic agents and colonic localization of disease are the major factors that are predictive of less aggressive CD course. The problem we face with determining the factors that increase the risk of disabling disease is that there is no standardized and consistent definition of disabling or aggressive disease. Only two studies analyzed predictors using the same definition of aggressive disease. Only Beaugerie and colleagues developed the score predictive of disabling disease based on three independent factors associated with disabling course that were present at the time of initial diagnosis of CD (requirement of corticosteroids, age less than 40 years, and presence of perianal disease). This score ranged from 0 to 3 points based on the presence of given parameters. The positive predictive value was 0.91 and 0.93 in patients having two or three risk factors, 0.61 for no factors present, and 0.67 for one factor present. In order to determine factors predictive of disabling CD there is a need to establish consistent definition of disabling disease with subsequent future studies on large group of patients to validate such definition and determine factors that may predict the aggressive course.
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Affiliation(s)
- Wojciech Blonski
- Division of Gastroenterology, University of Pennsylvania, Philadelphia, PA 19104-4283, USA
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Navaneethan U, Venkatesh PGK, Bennett AE, Patel V, Hammel J, Kiran RP, McCullough AJ, Shen B. Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis. J Crohns Colitis 2012; 6:536-42. [PMID: 22398056 DOI: 10.1016/j.crohns.2011.10.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2011] [Revised: 10/06/2011] [Accepted: 10/26/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Budesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA). MATERIALS AND METHODS The study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9 mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3 months followed by 3-6 mg maintenance for another 9 months. Demographic and clinical variables were analyzed. RESULTS The mean age was 39.4±12.4 years (range, 21-59 years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p=0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p=0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p=0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p=0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p=0.22] at the end of the treatment period (1 year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p=0.001). CONCLUSIONS Oral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients.
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Affiliation(s)
- Udayakumar Navaneethan
- Departments of Gastroenterology and Colorectal Surgery, Digestive Disease Institute, the Cleveland Clinic Foundation, Cleveland, OH, USA
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