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Are VS, Gromski MA, Akisik F, Vilar-Gomez E, Lammert C, Ghabril M, Vuppalanchi R, Chalasani N. Primary Sclerosing Cholangitis Limited to Intrahepatic Bile Ducts Has Distinctly Better Prognosis. Dig Dis Sci 2024; 69:1421-1429. [PMID: 38347369 DOI: 10.1007/s10620-023-08260-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 07/25/2023] [Indexed: 04/19/2024]
Abstract
BACKGROUND There are two sub-phenotypes of large-duct primary sclerosing cholangitis (PSC): isolated intrahepatic PSC (IIPSC) and extrahepatic disease with or without intrahepatic (extra/intrahepatic). AIMS This study examined the differences in outcomes in patients with IIPSC compared to extra/intrahepatic and small-duct PSC. METHODS Patients with PSC treated at our institution from 1998 to 2019 were investigated. Biochemistries, clinical events, and survival were assessed by chart review and National Death Index. Cox-proportional hazards were used to determine the risk of clinical outcomes based on biliary tract involvement. RESULTS Our cohort comprised 442 patients with large-duct PSC (57 had IIPSC, 385 had extra/intrahepatic PSC) and 23 with small-duct PSC. Median follow-up in the IIPSC group was not significantly different from the extra/intrahepatic group [7 vs. 6 years, P = 0.06]. Except for lower age (mean 37.9 vs. 43.0 years, P = 0.045), the IIPSC group was not different from the extra/intrahepatic. The IIPSC group had longer transplant-free survival (log-rank P = 0.001) with a significantly lower risk for liver transplantation (12% vs. 34%, P < 0.001). The IIPSC group had a lower risk of death or transplantation than the extra/intrahepatic PSC group [HR: 0.34, 95% CI: 0.17-0.67, P < 0.001]. No bile duct or gallbladder cancers developed in patients with IIPSC, compared to 24 in the extra/intrahepatic group. The clinical characteristics and outcomes of IIPSC were similar to 23 individuals with small-duct PSC. CONCLUSIONS Patients with IIPSC have a favorable prognosis similar to small-duct PSC. These data are important for counseling patients and designing therapeutic trials for PSC.
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Affiliation(s)
- Vijay S Are
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Mark A Gromski
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Fatih Akisik
- Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Eduardo Vilar-Gomez
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Craig Lammert
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Marwan Ghabril
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
| | - Raj Vuppalanchi
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA.
| | - Naga Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, 702 Rotary Circle, Suite 225, Indianapolis, IN, 46202, USA
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Gui W, Hole MJ, Molinaro A, Edlund K, Jørgensen KK, Su H, Begher-Tibbe B, Gaßler N, Schneider CV, Muthukumarasamy U, Mohs A, Liao L, Jaeger J, Mertens CJ, Bergheim I, Strowig T, Hengstler JG, Hov JR, Marschall HU, Trautwein C, Schneider KM. Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis. Nat Commun 2023; 14:3304. [PMID: 37280200 PMCID: PMC10244448 DOI: 10.1038/s41467-023-38840-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 05/18/2023] [Indexed: 06/08/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.
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Affiliation(s)
- Wenfang Gui
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Mikal Jacob Hole
- Norwegian PSC Research Center, Section of Gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Antonio Molinaro
- Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Karolina Edlund
- Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, 44139, Germany
| | - Kristin K Jørgensen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway
| | - Huan Su
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Brigitte Begher-Tibbe
- Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, 44139, Germany
| | - Nikolaus Gaßler
- Institute for Legal Medicine, Section Pathology, University Hospital, Jena, 07747, Germany
| | - Carolin V Schneider
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Uthayakumar Muthukumarasamy
- Helmholtz Centre for Infection Research, Braunschweig, Germany and Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, 97080, Germany
| | - Antje Mohs
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Lijun Liao
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
- Department of Anesthesiology and Pain Management, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China
| | - Julius Jaeger
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Christian J Mertens
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany
| | - Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Vienna, A-1090, Austria
| | - Till Strowig
- Helmholtz Centre for Infection Research, Braunschweig, Germany and Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, 97080, Germany
| | - Jan G Hengstler
- Leibniz Research Centre for Working Environment and Human Factors, Technical University Dortmund, Dortmund, 44139, Germany
| | - Johannes R Hov
- Norwegian PSC Research Center, Section of Gastroenterology and Research Institute of Internal Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital and University of Oslo, Oslo, Norway
| | - Hanns-Ulrich Marschall
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41345, Sweden
| | - Christian Trautwein
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany.
| | - Kai Markus Schneider
- Department of Medicine III, University Hospital RWTH Aachen, Aachen, 52074, Germany.
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Mazza S, Soro S, Verga MC, Elvo B, Ferretti F, Cereatti F, Drago A, Grassia R. Liver-side of inflammatory bowel diseases: Hepatobiliary and drug-induced disorders. World J Hepatol 2021; 13:1828-1849. [PMID: 35069993 PMCID: PMC8727201 DOI: 10.4254/wjh.v13.i12.1828] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 07/16/2021] [Accepted: 11/15/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatobiliary disorders are among the most common extraintestinal manifestations in inflammatory bowel diseases (IBD), both in Crohn’s disease and ulcerative colitis (UC), and therefore represent a diagnostic challenge. Immune-mediated conditions include primary sclerosing cholangitis (PSC) as the main form, variant forms of PSC (namely small-duct PSC, PSC-autoimmune hepatitis overlap syndrome and IgG4-related sclerosing cholangitis) and granulomatous hepatitis. PSC is by far the most common, presenting in up to 8% of IBD patients, more frequently in UC. Several genetic foci have been identified, but environmental factors are preponderant on disease pathogenesis. The course of the two diseases is typically independent. PSC diagnosis is based mostly on typical radiological findings and exclusion of secondary cholangiopathies. Risk of cholangiocarcinoma is significantly increased in PSC, as well as the risk of colorectal cancer in patients with PSC and IBD-related colitis. No disease-modifying drugs are approved to date. Thus, PSC management is directed against symptoms and complications and includes medical therapies for pruritus, endoscopic treatment of biliary stenosis and liver transplant for end-stage liver disease. Other non-immune-mediated hepatobiliary disorders are gallstone disease, whose incidence is higher in IBD and reported in up to one third of IBD patients, non-alcoholic fatty liver disease, pyogenic liver abscess and portal vein thrombosis. Drug-induced liver injury (DILI) is an important issue in IBD, since most IBD therapies may cause liver toxicity; however, the incidence of serious adverse events is low. Thiopurines and methotrexate are the most associated with DILI, while the risk related to anti-tumor necrosis factor-α and anti-integrins is low. Data on hepatotoxicity of newer drugs approved for IBD, like anti-interleukin 12/23 and tofacitinib, are still scarce, but the evidence from other rheumatic diseases is reassuring. Hepatitis B reactivation during immunosuppressive therapy is a major concern in IBD, and adequate screening and vaccination is warranted. On the other hand, hepatitis C reactivation does not seem to be a real risk, and hepatitis C antiviral treatment does not influence IBD natural history. The approach to an IBD patient with abnormal liver function tests is complex due to the wide range of differential diagnosis, but it is of paramount importance to make a quick and accurate diagnosis, as it may influence the therapeutic management.
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Affiliation(s)
- Stefano Mazza
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Sara Soro
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Maria Chiara Verga
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Biagio Elvo
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Francesca Ferretti
- Gastroenterology Unit, ASST Fatebenefratelli-Sacco, Department of Biomedical and Clinical Sciences (DIBIC), Università degli Studi di Milano, Milan 20157, Italy
| | - Fabrizio Cereatti
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Andrea Drago
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
| | - Roberto Grassia
- Gastroenterology and Digestive Endoscopy Unit, ASST Cremona, Cremona 26100, Italy
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Trivedi PJ, Hirschfield GM. Recent advances in clinical practice: epidemiology of autoimmune liver diseases. Gut 2021; 70:1989-2003. [PMID: 34266966 DOI: 10.1136/gutjnl-2020-322362] [Citation(s) in RCA: 130] [Impact Index Per Article: 32.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Accepted: 06/24/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune liver diseases are chronic inflammatory hepatobiliary disorders that when classically defined encompass three distinctive clinical presentations; primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). Meaningful changes in disease epidemiology are reported, with increasing incidence and prevalence of AIH and PSC in Europe, and rising prevalence of PBC across Europe, North America and the Asia-Pacific region. However, there appears to be very significant global variation with contemporary incidence rates of disease per 100 000 ranging from 0.84 to 2.75 for PBC, 0.1 to 4.39 for PSC and 0.4 to 2.39 for AIH. Prevalence corresponds, and per 100 000 estimates for PBC range from 1.91 to 40.2, for PSC between 0.78 and 31.7 and for AIH from 4.8 to 42.9. Population-based studies and multicentre observational cohort series provide improved understanding of the clinical course that patients experience, highlighting variations in presenting phenotypes geographically and temporally. Collectively, while autoimmune liver diseases are rare, the clinical burden is disproportionately high relative to population incidence and prevalence. Age, sex and race also impact clinical outcomes, and patient morbidity and mortality are reflected by high need for gastroenterology, hepatology and organ transplant services.
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Affiliation(s)
- Palak J Trivedi
- National Institute for Health Research (NIHR) Birmingham Liver Biomedical Research Centre, University of Birmingham College of Medical and Dental Sciences, Birmingham, Birmingham, UK
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
- Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, UK
| | - Gideon M Hirschfield
- Toronto Centre for Liver Disease, Division of Gastroenterology and Hepatology, University of Toronto, Toronto, Ontario, Canada
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5
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Guerra I, Bujanda L, Castro J, Merino O, Tosca J, Camps B, Gutiérrez A, Gordillo Ábalos J, de Castro L, Iborra M, Carbajo AY, Taxonera C, Rodríguez-Lago I, Mesonero F, de Francisco R, Gómez-Gómez GJ, Chaparro M, Tardillo CA, Rivero M, Algaba A, Martín Arranz E, Cañete F, Vicente R, Sicilia B, Antolín B, Prieto V, Márquez L, Benítez JM, Camo P, Piqueras M, Gargallo CJ, Hinojosa E, Huguet JM, Pérez Calle JL, Van Domselaar M, Rodriguez C, Calvet X, Muñoz-Villafranca C, García-Sepulcre MF, Munoz-Garrido P, Fernández-Clotet A, Gómez Irwin L, Hernández S, Guardiola J, Sempere L, González Muñoza C, Hernández V, Beltrán B, Barrio J, Alba C, Moraleja I, López-Sanromán A, Riestra S, Martínez Montiel P, Garre A, Arranz L, García MJ, Martín Arranz MD, Corsino P, Arias L, Fernández-Salazar L, Fernández-Pordomingo A, Andreu M, Iglesias E, Ber Y, Mena R, Arroyo Villarino MT, Mora M, Ruiz L, López-Serrano P, Blazquez I, Villoria A, Fernández M, Bermejo F, Banales JM, Domènech E, Gisbert JP. Clinical Characteristics, Associated Malignancies and Management of Primary Sclerosing Cholangitis in Inflammatory Bowel Disease Patients: A Multicentre Retrospective Cohort Study. J Crohns Colitis 2019; 13:1492-1500. [PMID: 31063540 DOI: 10.1093/ecco-jcc/jjz094] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. METHODS PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. RESULTS In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50-139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7-19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9-5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1-9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39-53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. CONCLUSIONS PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.
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Affiliation(s)
- Ivan Guerra
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Luis Bujanda
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | | | - Olga Merino
- Hospital Universitario de Cruces, Barakaldo, Vizcaya, Spain
| | - Joan Tosca
- Hospital Universitario Clínico de Valencia, Department of Medicine, University of Valencia, Valencia, Spain
| | - Blau Camps
- Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), l'Hospitalet de Llobregat, Spain
| | - Ana Gutiérrez
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | - Luisa de Castro
- Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica. Estructura Organizativa de Xestión Integrada de Vigo, Vigo, Spain
| | - Marisa Iborra
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | | | - Carlos Taxonera
- Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | | | | | - Ruth de Francisco
- Hospital Universitario Central De Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | - María Chaparro
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Carlos A Tardillo
- Hospital Universitario Nuestra Señora Candelaria, Santa Cruz De Tenerife, Spain
| | - Montserrat Rivero
- Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain
| | - Alicia Algaba
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Eduardo Martín Arranz
- Hospital Universitario La Paz and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid
| | - Fiorella Cañete
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | | | | | - Beatriz Antolín
- Hospital Clínico Universitario de Valladolid, Valladolid, Spain
| | | | | | - José M Benítez
- Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | | | - Carla J Gargallo
- Hospital Clínico Universitario "Lozano Blesa" and Aragón Health Research Institute (IIS Aragón), Zaragoza, Spain
| | | | - José M Huguet
- Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Manuel Van Domselaar
- Hospital Universitario de Torrejón and Universidad Francisco de Vitoria, Madrid, Spain
| | | | - Xavier Calvet
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Corporació Sanitària Universitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain
| | | | | | - Patricia Munoz-Garrido
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | | | | | - Sherly Hernández
- Hospital Universitario Clínico de Valencia, Department of Medicine, University of Valencia, Valencia, Spain
| | - Jordi Guardiola
- Hospital Universitari de Bellvitge, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), l'Hospitalet de Llobregat, Spain
- Universitat de Barcelona, Spain
| | - Laura Sempere
- Hospital General Universitario de Alicante, Alicante, Spain
| | | | - Vicent Hernández
- Complexo Hospitalario Universitario de Vigo, Instituto de Investigación Biomédica. Estructura Organizativa de Xestión Integrada de Vigo, Vigo, Spain
| | - Belén Beltrán
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario y Politécnico de La Fe, Valencia, Spain
| | | | - Cristina Alba
- Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
| | | | | | - Sabino Riestra
- Hospital Universitario Central De Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, Spain
| | | | - Ana Garre
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
| | - Laura Arranz
- Hospital Universitario Nuestra Señora Candelaria, Santa Cruz De Tenerife, Spain
| | - María José García
- Hospital Universitario Marqués de Valdecilla and IDIVAL, Santander, Spain
| | - María Dolores Martín Arranz
- Hospital Universitario La Paz and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid
| | - Pilar Corsino
- Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Lara Arias
- Hospital Universitario de Burgos, Burgos, Spain
| | | | | | | | - Eva Iglesias
- Hospital Universitario Reina Sofía and Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | | | | | | | | | - Lucía Ruiz
- Hospital General Universitario de Valencia, Valencia, Spain
| | | | - Isabel Blazquez
- Hospital Universitario de Torrejón and Universidad Francisco de Vitoria, Madrid, Spain
| | - Albert Villoria
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Complejo hospitalario de Navarra, Pamplona, Spain
| | - María Fernández
- Corporació Sanitària Universitària Parc Taulí, Universitat Autònoma de Barcelona, Sabadell, Spain
| | - Fernando Bermejo
- Hospital Universitario de Fuenlabrada and Instituto de Investigación del Hospital Universitario La Paz, IdiPaz, Madrid, Spain
| | - Jesus M Banales
- Hospital Donostia/Instituto Biodonostia, Universidad del País Vasco UPV/EHU, Donostia-San Sebastián, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Ikerbasque (Basque Foundation for Sciencies), Bilbao, Spain
| | - Eugeni Domènech
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Javier P Gisbert
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
- Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid, Madrid, Spain
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Vanishing Bile Duct Syndrome in a Patient with Uterine Cancer and Paraneoplastic Systemic Sclerosis. ACG Case Rep J 2019; 5:e95. [PMID: 30643839 PMCID: PMC6317838 DOI: 10.14309/crj.2018.95] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 09/12/2018] [Indexed: 01/20/2023] Open
Abstract
Vanishing bile duct syndrome (VBDS) is a rare entity of acquired disorders resulting in cholestasis secondary to progressive destruction of intrahepatic bile ducts. The syndrome has been described in the setting of autoimmune disorders, medication toxicities, genetic disorders, infectious etiologies, and in rare cases, neoplastic processes. There are no known case reports of VBDS in the setting of uterine malignancy. We present a case of VBDS in a patient with underlying uterine cancer complicated by paraneoplastic systemic sclerosis.
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7
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Isayama H, Tazuma S, Kokudo N, Tanaka A, Tsuyuguchi T, Nakazawa T, Notohara K, Mizuno S, Akamatsu N, Serikawa M, Naitoh I, Hirooka Y, Wakai T, Itoi T, Ebata T, Okaniwa S, Kamisawa T, Kawashima H, Kanno A, Kubota K, Tabata M, Unno M, Takikawa H. Clinical guidelines for primary sclerosing cholangitis 2017. J Gastroenterol 2018; 53:1006-1034. [PMID: 29951926 PMCID: PMC8930933 DOI: 10.1007/s00535-018-1484-9] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/11/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is relatively rare disease and pathogenesis and methods of treatments were still not established. Then, we had conducted the making clinical guidelines to manage patients with PSC based on the literature review and expert opinions. These clinical guidelines were made for the medical doctors on the management of PSC, except child case of PSC. METHODS We had employed modified Delphi method. The production committee decided guidelines, strength of recommendations and evidence level after reviewed literatures systematically, and The Expert panel evaluated those. The Scientific Committee of the Japan Biliary Association (JBA) evaluated revised guidelines, and the Public comments were collected on web site of JBA. RESULTS We had made 16 guidelines about epidemiology/pathophysiology, diagnostics, therapy and prognosis. Also, we had made both diagnostic and therapeutic flow chart. CONCLUSIONS We hope that these guidelines will contribute to the improvement and development of the medical care of PSC.
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Affiliation(s)
- Hiroyuki Isayama
- Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan
| | - Susumu Tazuma
- Department of General Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University Hospital, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Norihiro Kokudo
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Atsushi Tanaka
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Toshio Tsuyuguchi
- Department of Medicine and Gastroenterology, Chiba University, Chiba, Japan
| | - Takahiro Nakazawa
- Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan
| | - Kenji Notohara
- Department of Anatomic Pathology, Kurashiki Central Hospital, Kurashiki, Japan
| | - Suguru Mizuno
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Masahiro Serikawa
- Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Itaru Naitoh
- Department of Gastroenterology and Metabolism, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan
| | - Yoshiki Hirooka
- Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan
| | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takao Itoi
- Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan
| | - Tomoki Ebata
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shinji Okaniwa
- Department of Gastroenterology, Iida Municipal Hospital, Nagano, Japan
| | - Terumi Kamisawa
- Department of Internal Medicine, Tokyo Komagome Metropolitan Hospital, Tokyo, Japan
| | - Hiroki Kawashima
- Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Atsushi Kanno
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Keiichi Kubota
- Second Department of Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Masami Tabata
- Department of Surgery, Matsusaka Central General Hospital, Matsusaka, Mie, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | - Hajime Takikawa
- Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan
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Karlsen TH, Folseraas T, Thorburn D, Vesterhus M. Primary sclerosing cholangitis - a comprehensive review. J Hepatol 2017; 67:1298-1323. [PMID: 28802875 DOI: 10.1016/j.jhep.2017.07.022] [Citation(s) in RCA: 554] [Impact Index Per Article: 69.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 07/15/2017] [Accepted: 07/22/2017] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a rare disorder characterised by multi-focal bile duct strictures and progressive liver disease. Inflammatory bowel disease is usually present and there is a high risk of cholangiocarcinoma and colorectal cancer. Most patients ultimately require liver transplantation, after which disease recurrence may occur. With limited therapeutic options and a lack of proven surveillance strategies, patients currently have significant unmet needs. In the present seminar, we provide a comprehensive review of the status of the field. We emphasise developments related to patient stratification and disease behaviour, and provide an overview of management options from a practical, patient-centered perspective. We survey advances made in the understanding of PSC pathogenesis and summarise the ongoing efforts to develop an effective therapy based on these insights.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Norway; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway.
| | - Trine Folseraas
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway
| | - Douglas Thorburn
- UCL Institute for Liver and Digestive Health, Division of Medicine, University College London, UK; Sheila Sherlock Liver Centre, Royal Free London NHS Foundation Trust, London, UK
| | - Mette Vesterhus
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; National Centre for Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease affecting intra- and extrahepatic bile ducts, primarily the large biliary ducts. Clinical manifestations are broad, and the spectrum encompasses asymptomatic cholestasis, icteric cholangitis with pruritis, cirrhosis, and cholangiocarcinoma. Though rare, PSC has a propensity to affect young to middle-aged males and is strongly associated with inflammatory bowel disease. There is an unmet need for effective medical treatments for PSC, and to date, the only curative therapy is liver transplantation reserved for those with end-stage liver disease. This article addresses the diagnostic and management challenges of PSC, with a succinct analysis of existing therapies, their limitations, and a glimpse into the future of the management of this multifaceted pathologic entity.
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Affiliation(s)
- Sanjeev Sirpal
- Department of Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), University of Montreal, Montreal, QC
| | - Natasha Chandok
- Department of Medicine, University of Western Ontario, London, ON, Canada
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12
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Razzak A, Kozarek R. Diagnosis and endoscopic management of primary sclerosing cholangitis. TECHNIQUES IN GASTROINTESTINAL ENDOSCOPY 2016; 18:158-167. [DOI: 10.1016/j.tgie.2016.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are the most common chronic cholestatic liver diseases (CLD) in adults and are associated with immune mechanisms. PBC is considered a model autoimmune disease, and more than 90% of patients present very specific autoantibodies against mitochondrial antigens. Whether PSC should be considered an autoimmune or merely immune-mediated disease is still under debate. This review addresses the clinical relevance of autoantibodies in CLD and their pathogenic mechanisms and illustrates the technology available for appropriate autoantibody detection.
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Affiliation(s)
- Simona Marzorati
- Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via A. Manzoni 113, Rozzano, Milan 20089, Italy; Department of Electronics, Information and Bioengineering, Politecnico di Milano, via Ponzio 34/5, Milan 20133, Italy
| | - Pietro Invernizzi
- Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via A. Manzoni 113, Rozzano, Milan 20089, Italy; Division of Rheumatology, Allergy, and Clinical Immunology, University of California Davis, GBSF, 451 Health Science Drive, Davis, CA 95616, USA
| | - Ana Lleo
- Liver Unit and Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Via A. Manzoni 113, Rozzano, Milan 20089, Italy.
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Abstract
Sclerosing cholangitis in pediatric age is a severe disease, often associated with inflammatory bowel disease. It recognizes different etiologies. Management and prognosis depend on the underlying cause. A high proportion of patients have autoimmune features similar to those of autoimmune hepatitis and respond biochemically to immunosuppression, although bile duct disease progresses in half of them leading to liver transplant. The disease can recur after transplant. Severity of liver disease and risk of recurrence after transplant are linked to the severity of bowel disease.
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Affiliation(s)
- Giorgina Mieli-Vergani
- Paediatric Liver, GI and Nutrition Centre, King's College Hospital, Denmark Hill, London SE5 9RS, UK.
| | - Diego Vergani
- Institute of Liver Studies, King's College Hospital, Denmark Hill, London SE5 9RS, UK
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Abstract
Research related to primary sclerosing cholangitis (PSC) has since 1980 been a major activity at the Oslo University Hospital Rikshospitalet. The purpose of this publication is to describe the development of this research, the impact of this research on the clinical handling of the patients, and finally to describe what we believe are the most urgent, remaining problems to be solved. During the early years, our research dealt primarily with clinical aspects of the disease. The concomitant inflammatory bowel disease (IBD) seen in most patients with PSC was a major interest and we also started looking into genetic associations of PSC. Prognosis, malignancy development and treatment with special emphasis on transplantation have later been dealt with. These activities has had impact on several aspects of PSC management; when and how to diagnose PSC and variant forms of PSC, how to handle IBD in PSC and how to deal with the increased rate of malignancy? The problems remaining to be solved are many. What is the role of the gut and the gut microbiota in the development of PSC? Do the PSC patients have an underlying disturbance in the bile homeostasis? And how does the characteristic type of fibrosis in PSC develop? The genetic studies have supported a role for the adaptive immune system in the disease development, but how should this be dealt with? Importantly, the development of malignancy in PSC is still not understood, and we lack appropriate medical treatment for our patients.
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Affiliation(s)
- Erik Schrumpf
- Norwegian PSC research center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital Rikshospitalet , Oslo , Norway
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Abstract
Overlap syndrome in hepatology is emerging as a diagnostic and therapeutic challenge, which is further complicated by the present gaps in the information regarding the immunopathogenesis of these diseases. The present review represents a concise review of literature on overlap syndromes with emphasis on prevalence, etiopathogenesis, clinical presentation, diagnosis, and management of true overlap syndromes.
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Affiliation(s)
- Pooja Dhiman
- Department of Biochemistry, JIPMER, Dhanvantari Nagar, Puducherry, India
| | - Sharad Malhotra
- Department of Medical Gastroenterology, Batra Hospital and Medical Research Centre, New Delhi, India,Address for correspondence: Dr. Sharad Malhotra, Consultant, Medical Gastroenterology, Batra Hospital and Medical Research Centre, New Delhi, India. E-mail:
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Noble-Jamieson G, Heuschkel RB, Torrente F, Hadzic N, Zilbauer M. Colitis-associated sclerosing cholangitis in children: a single centre experience. J Crohns Colitis 2013; 7:e414-8. [PMID: 23485432 DOI: 10.1016/j.crohns.2013.01.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2012] [Revised: 01/26/2013] [Accepted: 01/26/2013] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Sclerosing cholangitis (SC) is an important immune-mediated extra-intestinal manifestation of inflammatory bowel disease (IBD), primarily affecting patients with ulcerative colitis (UC). The reported prevalence of SC in adults and children with UC is low at between 2 and 7%. We present findings from a hepatological work-up in children with inflammatory colitis and elevated liver function tests (LFT) from a tertiary paediatric gastroenterology unit. DESIGN This study is designed as a retrospective review of the medical records of 17 children and adolescents with inflammatory colitis and abnormal LFTs who presented to our IBD service between April 2004 and April 2012. RESULTS Over the eight year period a total of 52 patients were diagnosed with inflammatory colitis (ulcerative colitis and unclassified colitis). Seventeen of the 52 patients had abnormal liver function tests and underwent liver biopsy and cholangiography. All 17 patients (32.6%) were diagnosed with hepato-biliary disease. CONCLUSION This is one of the largest reported series of children with inflammatory colitis and associated hepato-biliary disease. The data from this patient group indicate that the prevalence of IBD-associated hepato-biliary disease in children with abnormal LFTs is much higher than previously reported. As the diagnosis of IBD-associated hepato-biliary disease affects patient management, we recommend liver biopsy and cholangiography in all children with inflammatory colitis and abnormal liver function tests.
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Affiliation(s)
- G Noble-Jamieson
- Department of Paediatric Gastroenterology, Addenbrooke's Hospital, Cambridge University, UK.
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Han Y, Glaser S, Meng F, Francis H, Marzioni M, McDaniel K, Alvaro D, Venter J, Carpino G, Onori P, Gaudio E, Alpini G, Franchitto A. Recent advances in the morphological and functional heterogeneity of the biliary epithelium. Exp Biol Med (Maywood) 2013; 238:549-65. [PMID: 23856906 DOI: 10.1177/1535370213489926] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
This review focuses on the recent advances related to the heterogeneity of different-sized bile ducts with regard to the morphological and phenotypical characteristics, and the differential secretory, apoptotic and proliferative responses of small and large cholangiocytes to gastrointestinal hormones/peptides, neuropeptides and toxins. We describe several in vivo and in vitro models used for evaluating biliary heterogeneity. Subsequently, we discuss the heterogeneous proliferative and apoptotic responses of small and large cholangiocytes to liver injury and the mechanisms regulating the differentiation of small into large (more differentiated) cholangiocytes. Following a discussion on the heterogeneity of stem/progenitor cells in the biliary epithelium, we outline the heterogeneity of bile ducts in human cholangiopathies. After a summary section, we discuss the future perspectives that will further advance the field of the functional heterogeneity of the biliary epithelium.
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Affiliation(s)
- Yuyan Han
- Department of Medicine, Division Gastroenterology, Texas A&M Health Science Center, College of Medicine, TX, USA
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Kummen M, Schrumpf E, Boberg KM. Liver abnormalities in bowel diseases. Best Pract Res Clin Gastroenterol 2013; 27:531-42. [PMID: 24090940 DOI: 10.1016/j.bpg.2013.06.013] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Accepted: 06/23/2013] [Indexed: 01/31/2023]
Abstract
Liver abnormalities are often seen in bowel diseases. Whether these represent aspects of two separate diseases, or if one is causing the other, is not always easy to decide. Extraintestinal manifestations of inflammatory bowel disease (IBD) or coeliac disease are frequently observed. Of these extraintestinal manifestations, hepatic disorders are among the most common. Primary sclerosing cholangitis (PSC) and primary biliary cirrhosis are the most frequent hepatic disorders in IBD and coeliac disease, respectively. Genetic studies have lately elucidated the associations between IBD and PSC, but there is still a long way until we have complete understanding of the molecular aetiology and pathophysiology of these conditions. There is no curative treatment available for PSC, besides liver transplantation. Steatosis and cholelithiasis are also common in IBD, as are signs of hepatic injury due to IBD treatment. Less common liver abnormalities include liver abscesses, hepatic thromboembolic events, granulomatous liver disease and hepatic amyloidosis.
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Affiliation(s)
- Martin Kummen
- Norwegian PSC Research Center, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Pb 4950 Nydalen, N-0424 Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
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20
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McGowan CE, Jones P, Long MD, Barritt AS. Changing shape of disease: nonalcoholic fatty liver disease in Crohn's disease-a case series and review of the literature. Inflamm Bowel Dis 2012; 18:49-54. [PMID: 21351214 PMCID: PMC3137748 DOI: 10.1002/ibd.21669] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2011] [Accepted: 01/10/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND With improvements in therapy for inflammatory bowel disease (IBD) and changes in the prevalence of obesity, the phenotype of Crohn's disease (CD) is changing. These changes may herald an increase in the incidence of nonalcoholic fatty liver disease (NAFLD) in this population. METHODS Over a 10-month period we identified seven patients with CD who required liver biopsy for elevated liver function tests (LFTs), with an ultimate diagnosis of NAFLD. We performed a retrospective chart review and literature search to identify relevant data on NAFLD and CD. Specifically, we abstracted prior and current IBD-related medication exposures, disease severity, and the presence of typical comorbidities associated with NAFLD. RESULTS We describe seven patients with CD and biopsy-proven NAFLD. The majority of these patients were overweight or obese, had quiescent CD, and were more likely to be receiving a tumor necrosis factor-alpha inhibitor. Review of the literature produced a total of 29 articles describing NAFLD in IBD patients, primarily restricted to historical autopsy and surgical series. Limited contemporary studies highlight the rising prevalence of NAFLD in treated IBD populations. CONCLUSIONS NAFLD is increasing in incidence and prevalence among the general population. With improvements in therapy, NAFLD is likely increasing among the CD population as well. When evaluating an IBD patient with abnormal LFTs, clinicians need to consider NAFLD. NAFLD may impact IBD management in the future if therapeutic modalities are limited due to elevated LFTs. Further, patients should be monitored for excessive weight gain and counseled regarding healthy dietary and exercise habits.
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Affiliation(s)
- Christopher E McGowan
- Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, 27599-7080, USA.
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Quaglia A, Burt AD, Ferrell LD, Portmann BC. Systemic disease. MACSWEEN'S PATHOLOGY OF THE LIVER 2012:935-986. [DOI: 10.1016/b978-0-7020-3398-8.00016-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Gnanaraj J, Fiedler P, Virata M. Vanishing bile duct syndrome in a HIV patient on HAART therapy. BMJ Case Rep 2011; 2011:bcr.06.2011.4369. [PMID: 22679317 DOI: 10.1136/bcr.06.2011.4369] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Vanishing bile duct syndrome refers to a group of disorders characterised by progressive destruction of the intrahepatic bile ducts resulting in cholestasis. It is a final common pathway for many disorders. The diagnoses is mainly made by histological findings. To consider a diagnosis there should be loss of interlobular bile ducts in more than fifty per cent of small portal tracts provided that the specimen contains at least 10 portal tracts. Here the authors present a case of vanishing bile duct syndrome which developed after initiation of highly active antiretroviral treatment therapy.
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Affiliation(s)
- Jerome Gnanaraj
- Department of Internal Medicine, Hospital of Saint Raphael, New Haven, Connecticut, United States.
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23
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Thakker A, Karande S. Overlap syndrome: autoimmune sclerosing cholangitis. Indian Pediatr 2011; 47:1063-5. [PMID: 21220805 DOI: 10.1007/s13312-010-0164-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
A 9-year-old-girl presented with clinical features of autoimmune hepatitis and associated signs of cholestasis in the form of itching and elevated levels of serum alkaline phosphatase. There was histologic evidence of bile duct injury. Hence a clinical diagnosis of "overlap syndrome" of autoimmune hepatitis with primary sclerosing cholangitis was considered.
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Affiliation(s)
- Arpita Thakker
- Department of Pediatrics, Lokmanya Tilak Municipal Medical College and General Hospital, Sion, Mumbai 400 022, India.
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Singal AK, Stanca CM, Clark V, Dixon L, Levy C, Odin JA, Fiel MI, Friedman SL, Bach N. Natural history of small duct primary sclerosing cholangitis: a case series with review of the literature. Hepatol Int 2011; 5:808-13. [PMID: 21484124 DOI: 10.1007/s12072-011-9260-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2010] [Accepted: 02/04/2011] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Information about the natural history of small duct primary sclerosing cholangitis (SDPSC) remains scant despite literature suggesting that it constitutes 6-16% of all cases of primary sclerosing cholangitis (PSC). We combined clinical data on SDPSC cases from two tertiary care institutions with liver transplantation programs with the aim of studying the natural history of SDPSC. METHODS Medical records of 25 individuals with SDPSC were reviewed. Diagnosis of SDPSC was based on liver biopsy findings consistent with PSC, a normal cholangiogram, and elimination of known causes of secondary sclerosing cholangitis. Demographic information, symptoms, past medical history, laboratory values, and histologic data were evaluated. Our primary outcome measure was liver transplantation or death. Secondary outcome measures included evidence of end-stage liver disease, development of cholangiocarcinoma, and/or the development of classic PSC on a repeat cholangiogram. RESULTS Data on 25 individuals (13 males, 12 females; mean age 40 ± 15 years) diagnosed with SDPSC were analyzed. Upon presentation, 11 patients had symptoms including abdominal pain, fatigue, and pruritus. Inflammatory bowel disease was present in 14 patients (56%) at diagnosis. On initial liver biopsy, 60% had early-stage disease (I or II) and none had cirrhosis. On follow-up (1-168 months, median 17 months), malignancy or progression to classic large duct PSC was not noted. Two (8%) patients had evidence of varices and one of the two also developed ascites; one of these patients underwent liver transplantation and the other one died due to sepsis. CONCLUSIONS SDPSC, a mild disease at presentation typically runs a benign course and likely is not an early stage of classic PSC. Further studies with a control group of classic PSC and longer follow-up are needed to study the natural history of SDPSC.
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Affiliation(s)
- A K Singal
- Department of Gastroenterology, University of Texas Medical Branch, Galveston, TX, USA
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Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue. J Hepatol 2011; 54:374-85. [PMID: 21067838 DOI: 10.1016/j.jhep.2010.09.002] [Citation(s) in RCA: 324] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2010] [Revised: 08/30/2010] [Accepted: 09/02/2010] [Indexed: 12/12/2022]
Abstract
Some patients present with overlapping features between disorders within the spectrum of autoimmune liver diseases (i.e. autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC)) and are commonly classified as having an "overlap syndrome". Standardized definitions of "overlap syndromes" are lacking. The aim of this report by the International Autoimmune Hepatitis Group (IAIHG) is to evaluate if there are important reasons to classify conditions with overlapping features between autoimmune liver diseases as separate diagnostic entities. Definition of diagnostic criteria for overlap conditions can only be arbitrary. The IAIHG scoring system for diagnosis of AIH has been widely used to diagnose "overlap syndromes", but was not intended for such use and has not proven to be an efficient tool for this purpose. Some patients with overlapping features between a cholestatic and hepatitic disorder appear to benefit from treatment with a combination of ursodeoxycholic acid and immunosuppressants, but this strategy is not evidence-based, and it seems unjustified to define new diagnostic groups in this regard. The IAIHG suggests that patients with autoimmune liver disease should be categorized according to the predominating feature(s) as AIH, PBC, and PSC/small duct PSC, respectively, and that those with overlapping features are not considered as being distinct diagnostic entities. The IAIHG scoring system should not be used to establish subgroups of patients. Patients with PBC and PSC with features of AIH should be considered for immunosuppressive treatment. Due to the low prevalence of such "overlap syndromes", prospective interventional therapeutic trials cannot be expected in the foreseeable future.
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Nayudu SK, Kumbum K, Balar B, Niazi M, Chilimuri S. Small Duct Primary Sclerosing Cholangitis in Association With Hepatitis C Virus Infection: A Case Report. Gastroenterology Res 2011; 4:39-41. [PMID: 27957013 PMCID: PMC5139801 DOI: 10.4021/gr282w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/24/2011] [Indexed: 12/13/2022] Open
Abstract
Small duct primary sclerosing cholangitis (PSC) is characterized by cholestatic liver function tests, histological evidence of PSC but absence of classic cholangiographic findings. Large duct or classic PSC in association with hepatitis C virus (HCV) infection has rarely been reported. However to the best of our knowledge small duct PSC in association with HCV infection has not been reported. We report this case of small duct PSC in a patient with HCV infection. HCV infection in our patient was successfully treated with ribavirin and peg interferon alfa-2a, as evidenced by undetectable HCV ribonucleic acid levels. However, the patient had persistently elevated liver function tests suggestive of cholestasis. Endoscopic retrograde cholangiopancreatography (ERCP) revealed normal architecture of bile ducts. Hence patient underwent liver biopsy and its histopahological findings were suggestive of PSC. He had colonoscopy along with biopsy and inflammatory bowel disease (IBD) was ruled out.
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Affiliation(s)
- Suresh Kumar Nayudu
- Department of Medicine, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
| | - Kavitha Kumbum
- Division of Gastroenterology, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
| | - Bhavna Balar
- Division of Gastroenterology, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
| | - Masooma Niazi
- Department of Pathology, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
| | - Sridhar Chilimuri
- Department of Medicine, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
- Division of Gastroenterology, Bronx Lebanon Hospital Center, Affiliated to Albert Einstein College of Medicine, Bronx, NY, USA
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Poropat G, Giljaca V, Stimac D, Gluud C, Cochrane Hepato‐Biliary Group. Bile acids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2011; 2011:CD003626. [PMID: 21249655 PMCID: PMC7163275 DOI: 10.1002/14651858.cd003626.pub2] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Primary sclerosing cholangitis is a progressive chronic cholestatic liver disease that usually leads to the development of cirrhosis. Studies evaluating bile acids in the treatment of primary sclerosing cholangitis have shown a potential benefit of their use. However, no influence on patients survival and disease outcome has yet been proven. OBJECTIVES To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Library, MEDLINE, EMBASE and Science Citation Index Expanded generally from inception through to October 2010. SELECTION CRITERIA Randomised clinical trials comparing any dose of bile acids or duration of treatment versus placebo, no intervention, or another intervention were included irrespective of blinding, language, or publication status. DATA COLLECTION AND ANALYSIS Two authors extracted data independently. We evaluated the risk of bias of the trials using prespecified domains. We performed the meta-analysis according to the intention-to-treat principle. We presented outcomes as relative risks (RR) or mean differences (MD), both with 95% confidence intervals (CI). MAIN RESULTS Eight trials evaluated ursodeoxycholic acid versus placebo or no intervention (592 patients). The eight randomised clinical trials have a high risk of bias. Patients were treated for three months to six years (median three years). The dosage of ursodeoxycholic acid used in the trials ranged from low (10 mg/kg body weight/day) to high (28 to 30 mg/kg body weight/day). Ursodeoxycholic acid did not significantly reduce the risk of death (RR 1.00; 95% CI 0.46 to 2.20); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 1.22; 95% CI 0.91 to 1.64); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.60; 95% CI 0.23 to 1.57). Ursodeoxycholic acid significantly improved serum bilirubin (MD -14.6 µmol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (MD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (MD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (MD -260 IU/litre; 95% CI -315 to -205), but not albumin (MD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was safe and well tolerated by patients with primary sclerosing cholangitis. AUTHORS' CONCLUSIONS We did not find enough evidence to support or refute the use of bile acids in the treatment of primary sclerosing cholangitis. However, bile acids seem to lead to a significant improvement in liver biochemistry. Therefore, more randomised trials are needed before any of the bile acids can be recommended for this indication.
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Affiliation(s)
- Goran Poropat
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Vanja Giljaca
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Davor Stimac
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Karlsen TH, Schrumpf E, Boberg KM. Update on primary sclerosing cholangitis. Dig Liver Dis 2010; 42:390-400. [PMID: 20172772 DOI: 10.1016/j.dld.2010.01.011] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2009] [Accepted: 01/17/2010] [Indexed: 02/06/2023]
Abstract
Early studies in primary sclerosing cholangitis (PSC) were concerned with disease characterization, and were followed by epidemiological studies of PSC and clinical subsets of PSC as well as a large number of treatment trials. Recently, the molecular pathogenesis and the practical handling of the patients have received increasing attention. In the present review we aim to give an update on the pathogenesis of PSC and cholangiocarcinoma in PSC, as well as to discuss the current opinion on diagnosis and treatment of PSC in light of the recent European Association for the Study of the Liver and the American Association for the Study of Liver Diseases practice guidelines.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Medical Department, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Abstract
Treatment decisions in autoimmune hepatitis are complicated by the diversity of its clinical presentations, uncertainties about its natural history, evolving opinions regarding treatment end points, varied nature of refractory disease, and plethora of alternative immunosuppressive agents. The goals of this article are to review the difficult treatment decisions and to provide the bases for making sound therapeutic judgments. The English literature on the treatment problems in autoimmune hepatitis were identified by Medline search up to October 2009 and 32 years of personal experience. Autoimmune hepatitis may have an acute severe presentation, mild inflammatory activity, lack autoantibodies, exhibit atypical histological changes (centrilobular zone 3 necrosis or bile duct injury), or have variant features reminiscent of another disease (overlap syndrome). Corticosteroid therapy must be instituted early, applied despite the absence of symptoms, or modified in an individualized fashion. Pursuit of normal liver tests and tissue is the ideal treatment end point, but this objective must be tempered against the risk of side effects. Relapse after treatment withdrawal requires long-term maintenance therapy, preferably with azathioprine. Treatment failure or an incomplete response warrants salvage therapy that can include conventional medications in modified dose or empirical therapies with calcineurin inhibitors or mycophenolate mofetil. Liver transplantation supersedes empirical drug therapy in decompensated patients. Elderly and pregnant patients warrant treatment modifications. Difficult treatment decisions in autoimmune hepatitis can be simplified by recognizing its diverse manifestations and individualizing treatment, pursuing realistic goals, applying appropriate salvage regimens, and identifying problematic patients early.
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Giljaca V, Poropat G, Stimac D, Gluud C, Cochrane Hepato‐Biliary Group. Glucocorticosteroids for primary sclerosing cholangitis. Cochrane Database Syst Rev 2010; 2010:CD004036. [PMID: 20091555 PMCID: PMC7163281 DOI: 10.1002/14651858.cd004036.pub3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis is a chronic cholestatic disease of intrahepatic and extrahepatic biliary ducts, characterised by chronic periductal inflammation and sclerosis of the ducts, which results in segmental stenoses of bile ducts, cholestasis, fibrosis, and ultimately, liver cirrhosis. Patients with primary sclerosing cholangitis are at higher risk of cholangiocarcinoma as well as of colonic neoplasia, since primary sclerosing cholangitis is associated with inflammatory bowel disease in more than 80% of the patients. Several therapeutic modalities have been proposed for primary sclerosing cholangitis, like ursodeoxycholic acid, glucocorticosteroids, and immunomodulatory agents, but none has been successful in reversing the process of the disease. To date, liver transplantation is the only definite therapeutic solution for patients with advanced primary sclerosing cholangitis with liver cirrhosis. OBJECTIVES To assess the beneficial and harmful effects of glucocorticosteroids for patients with primary sclerosing cholangitis. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and LILACS from their inception until September 2009, as well as reference lists. SELECTION CRITERIA Randomised clinical trials comparing any dose or duration of glucocorticosteroids versus placebo, no intervention, or other immunosuppressive agents. We included trials irrespective of language, blinding, or publication status. DATA COLLECTION AND ANALYSIS Authors extracted data independently and assessed the methodological quality by the generation of the allocation sequence, allocation concealment, double blinding, follow-up, incomplete outcome data reporting, selective reporting, baseline imbalance, and early stopping. The results of the meta-analyses were presented as relative risks (RR) or mean difference (MD), both with 95% confidence intervals (CI). The primary outcome measures were mortality and liver-related morbidity. MAIN RESULTS Two randomised clinical trials were eligible for inclusion. One trial compared biliary lavage with hydrocortisone versus saline in 17 patients. Hydrocortisone tended to increase adverse events (pancreatitis, cholangitis with septicaemia, paranoid ideas, fluid retention) (RR 3.43, 95% CI 0.51 to 22.9) and had no cholangiographic improvement, which led to termination of the trial. The other trial compared budesonide versus prednisone in 18 patients. Patients had statistically significant higher serum bilirubin concentration after treatment with prednisone compared with budesonide (MD 10.4 micromol/litre, 95% CI 1.16 to 19.64 micromol/litre). No other statistically significant effects on clinical or biochemical outcomes were reported on any of the evaluated interventions. AUTHORS' CONCLUSIONS There is no evidence to support or refute peroral glucocorticosteroids for patients with primary sclerosing cholangitis. The intrabiliary application of corticosteroids via nasobiliary tube seems to induce severe adverse effects.
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Affiliation(s)
- Vanja Giljaca
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Goran Poropat
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Davor Stimac
- Clinical Hospital Centre RijekaDepartment of GastroenterologyKresimirova 42RijekaCroatia51000
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Olsson R, Glaumann H, Almer S, Broomé U, Lebrun B, Bergquist A, Björnsson E, Prytz H, Danielsson A, Lindgren S. High prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis. Eur J Intern Med 2009; 20:190-6. [PMID: 19327611 DOI: 10.1016/j.ejim.2008.06.004] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2007] [Revised: 06/05/2008] [Accepted: 06/09/2008] [Indexed: 12/18/2022]
Abstract
BACKGROUND Overlap syndrome is a term used for overlapping features of autoimmune hepatitis and primary sclerosing cholangitis or primary biliary cirrhosis and for autoimmune cholangitis. We describe a high prevalence of small duct primary sclerosing cholangitis among patients with overlapping autoimmune hepatitis and primary sclerosing cholangitis. METHODS We sought to retrieve all patients with overlap syndrome between primary sclerosing cholangitis and autoimmune hepatitis in six university hospitals in Sweden. The revised autoimmune hepatitis scoring system proposed by the International Autoimmune Hepatitis Group was used to establish the diagnosis autoimmune hepatitis. Endoscopic retrograde cholangiography and/or magnetic resonance cholangiography were used to separate the primary sclerosing cholangitis cases diagnosed through liver biopsy into small and large primary sclerosing cholangitis. A histological diagnosis compatible with both autoimmune hepatitis and primary sclerosing cholangitis was required for inclusion. RESULTS 26 patients fulfilled our criteria for histological overlap of autoimmune hepatitis and primary sclerosing cholangitis, 7 (27%) of which had small duct primary sclerosing cholangitis. The reliability of the diagnosis small duct primary sclerosing cholangitis was supported by a very close similarity between small and large duct primary sclerosing cholangitis patients in clinical and laboratory data, and by a poor response to immunosuppressive therapy in the small duct primary sclerosing cholangitis patients. Patients with large duct overlap syndrome had a good response to immunosuppressive therapy. In both groups, our limited experience from ursodeoxycholic acid was largely poor. CONCLUSIONS Small duct primary sclerosing cholangitis is prevalent in the overlap syndrome between autoimmune hepatitis and primary sclerosing cholangitis.
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Affiliation(s)
- Rolf Olsson
- Department of Medicine, Sahlgrenska University Hospital/Sahlgrenska, Goteborg, Sweden.
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Abstract
The aetiology of primary sclerosing cholangitis (PSC) is not known and controversy exists as to whether PSC should be denominated an autoimmune disease. A large number of autoantibodies have been detected in PSC patients, but the specificity of these antibodies is generally low, and the frequencies vary largely between different studies. The presence of autoantibodies in PSC may be the result of a nonspecific dysregulation of the immune system, but the literature in PSC points to the possible presence of specific antibody targets in the biliary epithelium and in neutrophil granulocytes. The present review aims to give an overview of the studies of autoantibodies in PSC, with a particular emphasis on the prevalence, clinical relevance and possible pathogenetic importance of each individual marker.
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The challenges in primary sclerosing cholangitis--aetiopathogenesis, autoimmunity, management and malignancy. J Hepatol 2008; 48 Suppl 1:S38-57. [PMID: 18304683 DOI: 10.1016/j.jhep.2008.01.020] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by progressive inflammation and fibrosis of the bile ducts, resulting in biliary cirrhosis and is associated with a high risk of cholangiocarcinoma. The majority of patients are young, male and have coexisting inflammatory bowel disease. PSC is found with a prevalence of 10/100,000 in Northern European populations. The pathophysiology of PSC is a complex multistep process including immunological mechanisms, immunogenetic susceptibility and disorders of the biliary epithelia. The diagnosis is primarily based on endoscopic cholangiography although magnetic resonance imaging is increasingly used; biochemistry and immunoserology as well as histology play only a minor role. Due to the high risk of developing cholangiocarcinoma and also other tumours of the GI tract, surveillance strategies are essential, however they have yet to be established and evaluated. Biochemical parameters, clinical risk factors, endoscopic procedures and imaging techniques contribute to the early identification of patients at risk. Since medical therapy of PSC with ursodeoxycholic acid does not improve survival, to date, liver transplantation is the only option with a cure potential; if transplantation is accurately timed, transplanted PSC patients have an excellent rate of survival. However if cholangiocarcinoma is detected, a curative treatment is not possible in the majority of cases. The present review critically summarizes the current knowledge on the aetiopathogenesis of PSC and gives an overview of the diagnostic approaches, surveillance strategies and therapeutic options. Primary sclerosing cholangitis is a disease of unknown aetiology and without any further curative treatment options apart from liver transplantation. Therefore it may be regarded as the greatest challenge in hepatology today.
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Hirschfield GM, Heathcote EJ. Antimitochondrial antibody-negative primary biliary cirrhosis. Clin Liver Dis 2008; 12:323-31; viii-ix. [PMID: 18456183 DOI: 10.1016/j.cld.2008.02.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Primary biliary cirrhosis (PBC) is considered a classic autoimmune disease insofar as 95% of patients are seropositive for specific antimitochondrial antibodies (AMA). Yet it is still the case that the remaining 5% of patients have equivalent disease but test persistently AMA negative. Although variations exist in the immunologic profile of these patients, clinically there are no discernable differences, and although the diagnostic threshold is higher, the treatment and prognosis mirror that of classic disease. Previous terminology, therefore, has been abandoned in favor of the description, AMA-negative PBC.
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Affiliation(s)
- Gideon M Hirschfield
- Toronto Western Hospital, University Health Network, University of Toronto, 399 Bathurst Street, 6B Fell, Room 154, Toronto, Ontario M5T 2S8, Canada
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Abstract
Perhaps no condition associated with chronic cholestasis is less understood than vanishing bile duct syndrome, a term that refers loosely to the group of acquired disorders associated with progressive destruction and disappearance of the intrahepatic bile ducts and, ultimately, cholestasis. Although the array of insults resulting in poor bile flow is vast, most adult patients who have chronic cholestasis have either primary biliary cirrhosis (or primary sclerosing cholangitis; in some cases, however, a cause cannot be identified. This article reviews the multiple causes, postulated pathophysiology, clinical features, and treatment options for this syndrome.
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Affiliation(s)
- Nancy S Reau
- Center for Liver Diseases, Section of Gastroenterology, Department of Medicine, University of Chicago Medical Center, 5841 S. Maryland, MC7120, Chicago, IL 60637, USA.
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36
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Abstract
This article describes the connection between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). The two conditions have chronicity, liver inflammation, and a positive autoimmune serology in common; they differ in terms of gender distribution and bile duct damage. There is evidence suggesting that AIH and PSC are immune-mediated diseases. PSC and AIH could lie within the spectrum of the same disease process. Future studies should determine how frequently AIH evolves to PSC.
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Affiliation(s)
- Diego Vergani
- Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, Denmark Hill, London SE5 9RS, UK.
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Affiliation(s)
- Folashade A. Jose
- Department of Pediatric Gastroenterology, Hepatology, and Nutrition, University of California, San Francisco
| | - Melvin B. Heyman
- Department of Pediatrics, University of California, San Francisco
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Saich R, Chapman R. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease. World J Gastroenterol 2008; 14:331-7. [PMID: 18200656 PMCID: PMC2679122 DOI: 10.3748/wjg.14.331] [Citation(s) in RCA: 82] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease (IBD) affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence (up to 3.6%) in Crohn's disease. The strength of this association means that the vast majority (> 90%) of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fifth decade of life with a strong male predominance. Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ileitis and has a high risk of pouchitis post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis (AIH) is also more prevalent in patients with IBD, with up to 16% of patients with AIH also having ulcerative colitis. A small subgroup of patients have a AIH-PSC overlap syndrome and the management of these patients depends on liver histology, serum IgM levels, autoantibodies, degree of biochemical cholestasis and cholangiography as some of these patients may respond to immunosupression.
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Charatcharoenwitthaya P, Angulo P, Enders FB, Lindor KD. Impact of inflammatory bowel disease and ursodeoxycholic acid therapy on small-duct primary sclerosing cholangitis. Hepatology 2008; 47:133-42. [PMID: 17992695 DOI: 10.1002/hep.21960] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
UNLABELLED A longitudinal, cohort study was performed to characterize the clinical features of patients with small-duct primary sclerosing cholangitis (PSC) occurring with and without inflammatory bowel disease (IBD) and to determine the influence of IBD and the effect of ursodeoxycholic acid (UDCA) therapy on the course of the liver disease. Forty-two patients with small-duct PSC (14 women and 28 men; mean age, 36.7 +/- 13.3 years) were followed for up to 24.9 years. At presentation, prevalence of signs of liver disease (none versus 35%, P = 0.002), gastroesophageal varices (5% versus 30%, P = 0.03), and stage III/IV disease (9% versus 45%, P = 0.008) were lower in those with IBD versus those without IBD. During follow-up, 6 patients underwent liver transplantation, and another died of cirrhosis. Using the Cox proportional hazard analysis, concomitant IBD was not associated with liver death or transplant, whereas the revised Mayo risk score for PSC was the only prognostic factor associated with liver-related outcomes (relative risk, 6.47; 95% confidence interval, 1.75-137.5). UDCA (13-15 mg/kg/day) therapy for an average of 40 months showed biochemical improvement (P < 0.001) in UDCA-treated patients, while no significant change occurred in untreated patients. UDCA therapy had no effect on delaying progression of disease (relative risk, 0.95; 95% confidence interval, 0.38-2.36). CONCLUSION Small-duct PSC often is recognized at an early stage in patients with IBD; however, IBD has no impact on long-term prognosis. Although UDCA therapy improves liver biochemistries, it may not delay disease progression during the short period of treatment.
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Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population-based analysis. Am J Gastroenterol 2007; 102:1042-9. [PMID: 17313496 DOI: 10.1111/j.1572-0241.2007.01103.x] [Citation(s) in RCA: 171] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES The epidemiology of primary sclerosing cholangitis (PSC) has been incompletely assessed by population-based studies. We therefore conducted a population-based study to determine: (a) incidence rates of large and small duct PSC in adults and children, (b) the risk of inflammatory bowel disease on developing PSC, and (c) patterns of clinical presentation with the advent of magnetic resonance cholangiopancreatography (MRCP). METHODS All residents of the Calgary Health Region diagnosed with PSC between 2000 and 2005 were identified by medical records, endoscopic, diagnostic imaging, and pathology databases. Demographic and clinical information were obtained. Incidence rates were determined and risks associated with PSC were reported as rate ratios (RR) with 95% confidence intervals (CI). RESULTS Forty-nine PSC patients were identified for an age- and gender-adjusted annual incidence rate of 0.92 cases per 100,000 person-years. The incidence of small duct PSC was 0.15/100,000. In children the incidence rate was 0.23/100,000 compared with 1.11/100,000 in adults. PSC risk was similar in Crohn's disease (CD; RR 220.0, 95% CI 132.4-343.7) and ulcerative colitis (UC; RR 212.4, 95% CI 116.1-356.5). Autoimmune hepatitis overlap was noted in 10% of cases. MRCP diagnosed large duct PSC in one-third of cases. Delay in diagnosis was common (median 8.4 months). A minority had complications at diagnosis: cholangitis (6.1%), pancreatitis (4.1%), and cirrhosis (4.1%). CONCLUSIONS Pediatric cases and small duct PSC are less common than adult large duct PSC. Surprisingly, the risk of developing PSC in UC and CD was similar. Autoimmune hepatitis overlap was noted in a significant minority of cases.
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Affiliation(s)
- Gilaad G Kaplan
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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41
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Enns R. Primary Sclerosing Cholangitis. DISEASES OF THE GALLBLADDER AND BILE DUCTS 2006:306-331. [DOI: 10.1002/9780470986981.ch19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Nikolaidis NL, Giouleme OI, Tziomalos KA, Patsiaoura K, Kazantzidou E, Voutsas AD, Vassiliadis T, Eugenidis NP. Small-duct primary sclerosing cholangitis. A single-center seven-year experience. Dig Dis Sci 2005; 50:324-326. [PMID: 15745094 DOI: 10.1007/s10620-005-1604-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but without the typical cholangiographic changes are considered to have small-duct PSC. The incidence of small-duct PSC and the natural history still is not known. We performed a retrospective search for patients diagnosed with small-duct PSC between January 1997 and December 2003. The diagnosis of small-duct PSC was based on biochemical features of chronic cholestasis, liver biopsy findings consistent with PSC, and a normal cholangiogram on endoscopic retrograde cholangiography. Six patients fulfilled the diagnostic criteria for small-duct PSC. All patients received medical therapy. After a mean follow-up time of 26.0 +/- 29.8 months (range, 7-84 months), all patients are alive. Repeated liver biopsy was performed in one patient, 58 months after the initial one, and disclosed amelioration of histological findings (reduction in the Ludwig fibrosis score from 4 to 2). During follow-up symptoms disappeared in all patients who were symptomatic at diagnosis; none of those who were asymptomatic at diagnosis developed symptoms. At the time of last follow-up all patients showed significant improvement of their biochemical variables compared to baseline. Administration of aminosalicylates seemed to be of benefit irrespective of the presence of inflammatory bowel disease. No patients underwent liver transplantation or developed cholangiocarcinoma. Even though our study included a low number of patients and the follow-up time was relatively short, we can suggest that small-duct PSC rarely progresses to large-duct PSC and does not seem to be associated with development of cholangiocarcinoma. It thus seems to represent a separate entity with a favorable prognosis.
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Affiliation(s)
- Nikolaos L Nikolaidis
- Gastroenterology and Hepatology Section, Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Greece.
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Portincasa P, Vacca M, Moschetta A, Petruzzelli M, Palasciano G, van Erpecum KJ, van Berge-Henegouwen GP. Primary sclerosing cholangitis: updates in diagnosis and therapy. World J Gastroenterol 2005; 11:7-16. [PMID: 15609388 PMCID: PMC4205387 DOI: 10.3748/wjg.v11.i1.7] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2004] [Revised: 05/28/2004] [Accepted: 07/17/2004] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic syndrome of unknown origin mostly found in males, and characterized by diffuse inflammation and fibrosis of both intra- and extra-hepatic bile ducts. So far, PSC is considered as an autoimmune hepatobiliary disease. In most cases the progression of PSC towards liver cirrhosis and liver failure is slow but irreversible, and liver transplantation is currently the only definitive treatment. In recent years, PSC has been an area of active research worldwide with great interest in etiology, pathogenesis, diagnosis, and therapeutic options such as hydrophilic ursodeoxycholic acid and immunosuppressive agent tacrolimus. Recent updates on clinical and therapeutic aspects of PSC are discussed in the present review.
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Affiliation(s)
- Piero Portincasa
- Section of Internal Medicine, Department of Internal and Public Medicine (DIMIMP), University Medical School, Bari, Italy.
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44
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the intra- and extrahepatic bile ducts. An estimated 80% of patients in North America and Europe have coexistent inflammatory bowel disease (IBD). The underlying pathophysiology of PSC remains poorly understood. As a result, there is currently no effective medical therapy to halt disease progression. Important complications from PSC include metabolic bone disease, colorectal neoplasia, and cholangiocarcinoma. Liver transplantation remains the only successful treatment option for patients with advanced liver disease from PSC. A diagnosis of PSC should be considered among individuals with IBD and elevated serum liver biochemical tests.
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Affiliation(s)
- Jayant A Talwalkar
- Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA.
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45
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Abstract
BACKGROUND Glucocorticosteroids have been suggested for primary sclerosing cholangitis, which is characterised by chronic inflammation and fibrosis in the intrahepatic and extrahepatic biliary tree. OBJECTIVES To assess the beneficial and harmful effects of glucocorticosteroids for patients with primary sclerosing cholangitis. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials on The Cochrane Library, MEDLINE, EMBASE from their inception until March 2003, and reference lists. SELECTION CRITERIA Randomised clinical trials comparing any dose or duration of glucocorticosteroids versus placebo, no intervention, or other immunosuppressive agents. We included trials irrespective of language, blinding, or publication status. DATA COLLECTION AND ANALYSIS Both reviewers extracted data independently and assessed the methodological quality by the generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results of the meta-analyses were presented as relative risks or weighted mean difference (WMD), both with 95% confidence intervals (CI). The primary outcome measures were mortality and liver-related morbidity. MAIN RESULTS Two randomised clinical trials were eligible for inclusion. One trial compared biliary lavage with hydrocortisone versus saline in 17 patients. A significant number of adverse events (pancreatitis; cholangitis with septicaemia; paranoid ideas; fluid retention) and no cholangiographic improvement led to termination of the trial. The other trial compared budesonide versus prednisone in 18 patients. Patients had significantly higher serum bilirubin concentration after treatment with prednisone compared with budesonide (WMD 10.4 micro mol/litre, 95% CI 1.16 to 19.64 micro mol/litre). No other significant effects on clinical or biochemical outcomes were identified for any of the evaluated interventions. REVIEWERS' CONCLUSIONS There is no evidence to support or refute peroral glucocorticosteroids for patients with primary sclerosing cholangitis.
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Affiliation(s)
- W Chen
- Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7102, H:S Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK 2100 Copenhagen, Denmark
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Feldstein AE, Perrault J, El-Youssif M, Lindor KD, Freese DK, Angulo P. Primary sclerosing cholangitis in children: a long-term follow-up study. Hepatology 2003; 38:210-7. [PMID: 12830004 DOI: 10.1053/jhep.2003.50289] [Citation(s) in RCA: 145] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 +/- 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated gamma-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P <.001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P =.2) or medical therapy (P =.2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome.
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Affiliation(s)
- Ariel E Feldstein
- Division of Gastroenterology and Hepatology, Department of Pediatric and Adolescent Medicine, Mayo Medical School, Clinic and Foundation, Rochester, MN 55905, USA
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Abstract
BACKGROUND Bile acids have been used for treating primary sclerosing cholangitis, but their beneficial and harmful effects remain unclear. OBJECTIVES To assess the beneficial and harmful effects of bile acids for patients with primary sclerosing cholangitis. SEARCH STRATEGY We searched The Cochrane Hepato-Biliary Group's Trials Register, The Cochrane Library, MEDLINE, EMBASE, and The Chinese Biomedical Database generally from inception through to May 2002. SELECTION CRITERIA Randomised clinical trials comparing any dose or duration of bile acids versus placebo, no intervention, or another intervention were included. Trials were included irrespective of blinding, language, or publication status. DATA COLLECTION AND ANALYSIS Two reviewers extracted the data. The methodological quality of the trials was evaluated with respect to the generation of the allocation sequence, allocation concealment, double blinding, and follow-up. The results were reported by intention-to-treat analysis. The outcomes were presented as relative risks (RR) or weighted mean differences (WMD), both with 95% confidence intervals (CI). MAIN RESULTS We identified six randomised clinical trials, all with low methodological quality. Patients were treated for three months to six years (median two years). Five trials (183 patients) compared ursodeoxycholic acid versus placebo, and one trial (40 patients) compared ursodeoxycholic acid versus no treatment. Ursodeoxycholic acid did not significantly reduce the risk of death (RR 0.86; 95% CI 0.27 to 2.73); treatment failure including liver transplantation, varices, ascites, and encephalopathy (RR 0.94; 95% CI 0.63 to 1.42); liver histological deterioration (RR 0.89; 95% CI 0.45 to 1.74); or liver cholangiographic deterioration (RR 0.43; 95% CI 0.18 to 1.02). Ursodeoxycholic acid significantly improved serum bilirubin (WMD -14.6 micro mol/litre; 95% CI -18.7 to -10.6), alkaline phosphatases (WMD -506 IU/litre; 95% CI -583 to -430), aspartate aminotransferase (WMD -46 IU/litre; 95% CI -77 to -16), and gamma-glutamyltranspeptidase (WMD -260 IU/litre; 95% CI -315 to -205), but not albumin (WMD -0.20 g/litre; 95% CI -1.91 to 1.50). Ursodeoxycholic acid was well tolerated. REVIEWER'S CONCLUSIONS Ursodeoxycholic acid leads to a significant improvement in liver biochemistry, but there is insufficient evidence to either support or refute its clinical effects in patients with primary sclerosing cholangitis. Large scale, high-quality randomised clinical trials are needed.
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Affiliation(s)
- W Chen
- The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, H:S Rigshospitalet, Dept. 7102, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
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Ayata G, Gordon FD, Lewis WD, Pomfret E, Pomposelli JJ, Jenkins RL, Khettry U. Cryptogenic cirrhosis: clinicopathologic findings at and after liver transplantation. Hum Pathol 2002; 33:1098-104. [PMID: 12454814 DOI: 10.1053/hupa.2002.129419] [Citation(s) in RCA: 100] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The incidence of cryptogenic cirrhosis (CC) has decreased since the discovery of hepatitis C virus (HCV), still the etiology in 5% of cases with cirrhosis remains unresolved. Our aims were to define the clinicopathologic features of CC at liver transplantation (LT), evaluate the post-LT course with outcome and define the possible pathogenetic mechanisms. 27/534 LT recipients (5%) over a period of 16.5 years were entered in the LT database as cases of CC. A detailed analysis of pre- and post-LT clinical and all liver pathology specimens was performed. Based on clinicopathologic findings, a more definite diagnosis was possible in 23 of 27 (85%): Nonalcoholic steatohepatitis (NASH) in 9 (33%), autoimmune liver disease (AILD) in 6 (22%), alcoholic liver disease in 4, secondary biliary cirrhosis in 2 and 1 each of hepatitis C and portal venopathy. 4/27 cases remained unresolved. In the NASH group, native livers had focal steatosis, Mallory's hyalin, glycogenated hepatocytic nuclei, high-grade inflammation, and 3+ bile duct proliferation. Large cell dysplasia was more common in this group compared to other patients. Two patients had recurrence of NASH after LT. In AILD group native livers had little or no bile duct proliferation. Two patients had recurrence in AILD group. Of 27 patients 19 are alive (70%) with a follow-up of 407-3647 days. Based on the study results, the following conclusions were reached: (1) CC results from varying etiologies, which can be defined by a careful clinicopathologic analysis in a majority (85%) of cases; (2) Nonalcoholic steatohepatitis (33%) and AILD (22%) are the common underlying causes of CC; and (3) Post-LT outcome for CC is disease dependent with, recurrent disease seen in both nonalcoholic steatohepatitis (22%) and autoimmune liver disease (33%).
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Affiliation(s)
- Gamze Ayata
- Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
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Carpenter HA, Czaja AJ. The role of histologic evaluation in the diagnosis and management of autoimmune hepatitis and its variants. Clin Liver Dis 2002; 6:685-705. [PMID: 12362575 DOI: 10.1016/s1089-3261(02)00022-3] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The diagnosis of autoimmune hepatitis requires a constellation of clinical, laboratory, and histologic features that exclude other conditions and support the syndrome. Interface hepatitis is the histologic hallmark of the disease, and it may be associated with panacinar hepatitis with or without bridging necrosis or multiacinar necrosis. The liver tissue examination at accession supports the diagnosis and assesses disease severity. It can also suggest the diagnosis in patients with atypical presentations, including those with an acute onset or cryptogenic disease. The liver tissue examination during therapy defines end points of treatment (remission) and evaluates unexpected outcomes (treatment failure, incomplete response). Manifestations of bile duct injury are incompatible with the classic diagnosis of autoimmune hepatitis, and they may be coincidental findings of no or uncertain clinical significance or weak expressions of a variant form. Histologic features of autoimmune hepatitis may intermix with those of PBC, PSC, and chronic hepatitis C infection, or they may occur in autoimmune cholangitis or cryptogenic chronic hepatitis. Conditions in which the histologic findings suggest the overlap of two disorders or are insufficient for designation as classic disease constitute the variant syndromes.
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MESH Headings
- Biopsy, Needle
- Cholangitis, Sclerosing/diagnosis
- Cholangitis, Sclerosing/metabolism
- Cholangitis, Sclerosing/pathology
- Diagnosis, Differential
- Hepatitis C, Chronic/diagnosis
- Hepatitis C, Chronic/metabolism
- Hepatitis C, Chronic/pathology
- Hepatitis, Autoimmune/diagnosis
- Hepatitis, Autoimmune/metabolism
- Hepatitis, Autoimmune/pathology
- Hepatitis, Chronic/diagnosis
- Hepatitis, Chronic/metabolism
- Hepatitis, Chronic/pathology
- Histocytochemistry
- Humans
- Liver Cirrhosis, Biliary/diagnosis
- Liver Cirrhosis, Biliary/metabolism
- Liver Cirrhosis, Biliary/pathology
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Affiliation(s)
- Herschel A Carpenter
- Department of Laboratory Medicine and Pathology, Mayo Medical School, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
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Abstract
Some patients with inflammatory bowel disease (IBD) have chronic cholestasis and hepatic histology compatible with primary sclerosing cholangitis (PSC) but normal findings on cholangiography. These patients with small-duct PSC have remained largely unstudied. Our aim was to determine the prevalence and long-term outcomes of patients with small-duct PSC. Eighteen patients with small-duct PSC (7 female and 11 male patients; mean age, 39.9 +/- 15.3 years [range, 13-68 years]) seen over a 4-year period were matched blindly by age and sex to 36 patients with classic PSC and followed up for 32.5 years. Small-duct PSC represented 5.8% of patients (18 of 309) with sclerosing cholangitis. Subsequent endoscopic retrograde cholangiography (ERC) performed in 5 patients with small-duct PSC showed progression to typical PSC in 3 patients at 4, 5.5, and 21 years of follow-up. None of the patients with small-duct PSC but 4 of the patients with classic PSC developed hepatobiliary malignancy. There were 3 deaths (17%) or liver transplantations in patients with small-duct PSC (2 after progressing to classic PSC) and 15 (42%) in the classic PSC group. Survival free of liver transplantation was significantly greater in the small-duct than in the classic PSC group (P =.04). Compared with the general U.S. population, survival in patients with small-duct PSC was similar (P =.4) but significantly lower in patients with classic PSC (P <.001). In conclusion, small-duct PSC may represent an earlier stage of PSC associated with a significantly better long-term prognosis. Some patients, however, progress to classic PSC and/or end-stage liver disease with the consequent necessity of liver transplantation.
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Affiliation(s)
- Paul Angulo
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
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