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Hatia RI, Eluri M, Hawk ET, Shalaby A, Karatas E, Shalaby A, Abdelhakeem A, Abdel-Wahab R, Chang P, Rashid A, Jalal PK, Amos CI, Han Y, Armaghany T, Shroff RT, Li D, Javle M, Hassan MM. Independent of Primary Sclerosing Cholangitis and Cirrhosis, Early Adulthood Obesity Is Associated with Cholangiocarcinoma. Cancer Epidemiol Biomarkers Prev 2023; 32:1338-1347. [PMID: 37540502 DOI: 10.1158/1055-9965.epi-23-0388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 07/14/2023] [Accepted: 08/01/2023] [Indexed: 08/05/2023] Open
Abstract
BACKGROUND It is estimated that 6% to 20% of all cholangiocarcinoma (CCA) diagnoses are explained by primary sclerosing cholangitis (PSC), but the underlying risk factors in the absence of PSC are unclear. We examined associations of different risk factors with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States. METHODS We conducted a case-control study of 121 patients with ECC and 308 patients with ICC treated at MD Anderson Cancer Center between May 2014 and March 2020, compared with 1,061 healthy controls. Multivariable logistic regression analysis was applied to estimate the adjusted OR (AOR) and 95% confidence interval (CI) for each risk factor. RESULTS Being Asian, diabetes mellitus, family history of cancer, and gallbladder stones were associated with higher odds of developing ICC and ECC. Each 1-unit increase in body mass index in early adulthood (ages 20-40 years) was associated with a decrease in age at diagnosis of CCA (6.7 months, P < 0.001; 6.1 months for ICC, P = 0.001; 8.2 months for ECC, P = 0.007). A family history of cancer was significantly associated with the risk of ICC and ECC development; the AORs (95% CI) were 1.11 (1.06-1.48) and 1.32 (1.01-2.00) for ICC and ECC, respectively. CONCLUSIONS In this study, early adulthood onset of obesity was significantly associated with CCA and may predict early diagnosis at younger age than normal weight individuals. IMPACT The study highlights the association between obesity and CCA, independent of PSC. There is a need to consider the mechanistic pathways of obesity in the absence of fatty liver and cirrhosis.
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Affiliation(s)
- Rikita I Hatia
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Madhulika Eluri
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ernest T Hawk
- Division of Cancer Prevention & Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Akram Shalaby
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio
| | - Elif Karatas
- Department of Internal Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, New York
| | - Ahmed Shalaby
- Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, New Jersey
| | - Ahmed Abdelhakeem
- Department of Internal Medicine, Baptist Hospital of Southeast Texas, Beaumont, Texas
| | - Reham Abdel-Wahab
- Department of Melanoma Medicine Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
- Clinical Oncology Department, Faculty of Medicine, Assiut University, Assiut, Egypt
| | - Ping Chang
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Asif Rashid
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Prasun K Jalal
- Department of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas
| | - Christopher I Amos
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Younghun Han
- Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, Texas
| | - Tannaz Armaghany
- Division of Hematology & Oncology, Baylor College of Medicine, Houston, Texas
| | - Rachna T Shroff
- Division of Hematology/Oncology, University of Arizona Cancer Center, Tucson, Arizona
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Milind Javle
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Manal M Hassan
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Abstract
BACKGROUND Autoimmune hepatitis has an unknown cause and genetic associations that are not disease-specific or always present. Clarification of its missing causality and heritability could improve prevention and management strategies. AIMS Describe the key epigenetic and genetic mechanisms that could account for missing causality and heritability in autoimmune hepatitis; indicate the prospects of these mechanisms as pivotal factors; and encourage investigations of their pathogenic role and therapeutic potential. METHODS English abstracts were identified in PubMed using multiple key search phases. Several hundred abstracts and 210 full-length articles were reviewed. RESULTS Environmental induction of epigenetic changes is the prime candidate for explaining the missing causality of autoimmune hepatitis. Environmental factors (diet, toxic exposures) can alter chromatin structure and the production of micro-ribonucleic acids that affect gene expression. Epistatic interaction between unsuspected genes is the prime candidate for explaining the missing heritability. The non-additive, interactive effects of multiple genes could enhance their impact on the propensity and phenotype of autoimmune hepatitis. Transgenerational inheritance of acquired epigenetic marks constitutes another mechanism of transmitting parental adaptations that could affect susceptibility. Management strategies could range from lifestyle adjustments and nutritional supplements to precision editing of the epigenetic landscape. CONCLUSIONS Autoimmune hepatitis has a missing causality that might be explained by epigenetic changes induced by environmental factors and a missing heritability that might reflect epistatic gene interactions or transgenerational transmission of acquired epigenetic marks. These unassessed or under-evaluated areas warrant investigation.
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Affiliation(s)
- Albert J Czaja
- Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
- Professor Emeritus of Medicine, Mayo Clinic College of Medicine and Science, 200 First Street SW, Rochester, MN, 55905, USA.
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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: 117] [Impact Index Per Article: 29.3] [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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A brief history of carbon monoxide and its therapeutic origins. Nitric Oxide 2021; 111-112:45-63. [PMID: 33838343 DOI: 10.1016/j.niox.2021.04.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 02/03/2021] [Accepted: 04/01/2021] [Indexed: 02/06/2023]
Abstract
It is estimated that 10% of carbon throughout the cosmos is in the form of carbon monoxide (CO). Earth's earliest prebiotic atmosphere included the trinity of gasotransmitters CO, nitric oxide (NO), and hydrogen sulfide (H2S), for which all of life has co-evolved with. The history of CO can be loosely traced to mythological and prehistoric origins with rudimentary understanding emerging in the middle ages. Ancient literature is focused on CO's deadly toxicity which is understandable in the context of our primitive relationship with coal and fire. Scientific inquiry into CO appears to have emerged throughout the 1700s followed by chemical and toxicological profiling throughout the 1800s. Despite CO's ghastly reputation, several of the 18th and 19th century scientists suggested a therapeutic application of CO. Since 2000, the fundamental understanding of CO as a deadly nuisance has undergone a paradigm shift such that CO is now recognized as a neurotransmitter and viable pharmaceutical candidate. This review is intended to provide a brief history on the trace origins pertaining to endogenous formation and therapeutic application of CO.
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Hopper CP, De La Cruz LK, Lyles KV, Wareham LK, Gilbert JA, Eichenbaum Z, Magierowski M, Poole RK, Wollborn J, Wang B. Role of Carbon Monoxide in Host-Gut Microbiome Communication. Chem Rev 2020; 120:13273-13311. [PMID: 33089988 DOI: 10.1021/acs.chemrev.0c00586] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Nature is full of examples of symbiotic relationships. The critical symbiotic relation between host and mutualistic bacteria is attracting increasing attention to the degree that the gut microbiome is proposed by some as a new organ system. The microbiome exerts its systemic effect through a diverse range of metabolites, which include gaseous molecules such as H2, CO2, NH3, CH4, NO, H2S, and CO. In turn, the human host can influence the microbiome through these gaseous molecules as well in a reciprocal manner. Among these gaseous molecules, NO, H2S, and CO occupy a special place because of their widely known physiological functions in the host and their overlap and similarity in both targets and functions. The roles that NO and H2S play have been extensively examined by others. Herein, the roles of CO in host-gut microbiome communication are examined through a discussion of (1) host production and function of CO, (2) available CO donors as research tools, (3) CO production from diet and bacterial sources, (4) effect of CO on bacteria including CO sensing, and (5) gut microbiome production of CO. There is a large amount of literature suggesting the "messenger" role of CO in host-gut microbiome communication. However, much more work is needed to begin achieving a systematic understanding of this issue.
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Affiliation(s)
- Christopher P Hopper
- Institute for Experimental Biomedicine, University Hospital Wuerzburg, Wuerzburg, Bavaria DE 97080, Germany.,Department of Medicinal Chemistry, College of Pharmacy, The University of Florida, Gainesville, Florida 32611, United States
| | - Ladie Kimberly De La Cruz
- Department of Chemistry & Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
| | - Kristin V Lyles
- Department of Biology, Georgia State University, Atlanta, Georgia 30303, United States
| | - Lauren K Wareham
- The Vanderbilt Eye Institute and Department of Ophthalmology & Visual Sciences, The Vanderbilt University Medical Center and School of Medicine, Nashville, Tennessee 37232, United States
| | - Jack A Gilbert
- Department of Pediatrics, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92093, United States
| | - Zehava Eichenbaum
- Department of Biology, Georgia State University, Atlanta, Georgia 30303, United States
| | - Marcin Magierowski
- Cellular Engineering and Isotope Diagnostics Laboratory, Department of Physiology, Jagiellonian University Medical College, Cracow PL 31-531, Poland
| | - Robert K Poole
- Department of Molecular Biology and Biotechnology, The University of Sheffield, Firth Court, Sheffield S10 2TN, U.K
| | - Jakob Wollborn
- Department of Anesthesiology and Critical Care, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg DE 79085, Germany.,Department of Anesthesiology, Perioperative and Pain Management, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States
| | - Binghe Wang
- Department of Chemistry & Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, Georgia 30303, United States
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Zhang C, Hussaini T, Yoshida EM. Review of pharmacotherapeutic treatments for primary sclerosing cholangitis. CANADIAN LIVER JOURNAL 2019; 2:58-70. [PMID: 35990218 PMCID: PMC9202752 DOI: 10.3138/canlivj-2018-0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2018] [Accepted: 08/15/2018] [Indexed: 11/13/2023]
Abstract
BACKGROUND The objective of this review was to evaluate pharmacotherapeutic treatments for primary sclerosing cholangitis (PSC) through a literature search of current published data. A review of the current clinical data for each treatment is discussed. METHODS We conducted a systematic literature search for articles using EMBASE (1980 to April 1, 2018), and MEDLINE (1948 to April 1, 2018) using Ovid, to identify studies investigating various therapies in PSC. Search terms included the following: primary sclerosing cholangitis, cholangitis, sclerosing cholangitis; ursodeoxycholic acid, glucocorticoids, cyclosporine, tacrolimus, methotrexate, azathioprine, 6-mercaptopurine, penicillamine, anti-TNF, antibiotics, and probiotics. We also performed a review of current clinical trials using ClinicalTrials.gov. We considered for review relevant studies published in English, pilot studies, and randomized controlled trials involving human subjects. RESULTS Therapies that have been investigated in the management of PSC include those used in search terms and others that were not included in our search parameters. Analysis of published data involving each therapy was explored and none have shown any sustained, significant benefit in the treatment of PSC. In terms of relevance to patient care and clinical practice, this review evaluates and compares various pharmacotherapeutic treatments for PSC where liver transplantation remains the only definitive treatment. CONCLUSIONS To date, no clinical study of any drug has demonstrated effectiveness in terms of survival benefit or a decreased need for liver transplantation. More clinical studies are needed, and patients need to be adequately informed before any medical therapy for PSC is undertaken.
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Affiliation(s)
- Chaoran Zhang
- Internal Medicine Residency Training Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia;
| | - Trana Hussaini
- Department of Pharmaceutical Sciences Medicine, Vancouver General Hospital, Vancouver, British Columbia;
| | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia
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7
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Wijarnpreecha K, Panjawatanan P, Mousa OY, Cheungpasitporn W, Pungpapong S, Ungprasert P. Association between appendectomy and risk of primary sclerosing cholangitis: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2018; 42:436-442. [PMID: 29655526 DOI: 10.1016/j.clinre.2018.03.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Revised: 03/01/2018] [Accepted: 03/15/2018] [Indexed: 02/04/2023]
Abstract
BACKGROUND/OBJECTIVES Recent epidemiologic studies have suggested that appendectomy could be a risk factor for primary sclerosing cholangitis (PSC) although the results were inconsistent. This systematic review and meta-analysis was conducted to summarize all available evidence. METHODS A comprehensive literature review was conducted using MEDLINE and EMBASE database through January 2018 to identify all studies that reported the risk of PSC among individuals who had appendectomy versus those with no history of appendectomy. Effect estimates from each study were extracted and combined together using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS A total of 6 case-control studies with 2432 participants met the eligibility criteria and were included in the meta-analysis. The risk of PSC in individuals who had appendectomy was significantly higher than those with no history of appendectomy with the pooled odds ratio of 1.37 (95% CI: 1.15-1.63). The statistical heterogeneity was insignificant with an I2 of 0%. CONCLUSIONS A significantly increased risk of PSC among individuals who had a history of appendectomy was found in this study.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA.
| | | | - Omar Y Mousa
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Wisit Cheungpasitporn
- Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Surakit Pungpapong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Patompong Ungprasert
- Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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8
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Wijarnpreecha K, Panjawatanan P, Mousa OY, Cheungpasitporn W, Pungpapong S, Ungprasert P. Association between smoking and risk of primary sclerosing cholangitis: A systematic review and meta-analysis. United European Gastroenterol J 2018; 6:500-508. [PMID: 29881604 DOI: 10.1177/2050640618761703] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 02/05/2018] [Indexed: 12/15/2022] Open
Abstract
Background/Objectives Studies have suggested that smokers may have a lower risk of primary sclerosing cholangitis (PSC) although the results have been inconsistent. This systematic review and meta-analysis was conducted to summarize all available data to better characterize this association. Methods A comprehensive literature review was conducted using Medline and Embase databases through January 2018 to identify all studies that compared the risk of PSC among current/former smokers versus nonsmokers. Effect estimates from each study were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Results Seven case-control studies with 2,307,393 participants met the eligibility criteria and were included in the meta-analysis. The risk of PSC among current smokers and former smokers was significantly lower than nonsmokers with the pooled odds ratio of 0.31 (95% CI, 0.18-0.53) and 0.52 (95% CI, 0.44-0.61), respectively. The risk remained significantly lower among current smokers and former smokers compared with nonsmokers even when only patients with PSC without inflammatory bowel disease were included. Conclusions A significantly decreased risk of PSC among current and former smokers was demonstrated in this study.
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Affiliation(s)
- Karn Wijarnpreecha
- 1Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY, USA
| | | | - Omar Y Mousa
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Wisit Cheungpasitporn
- 4Department of Medicine, Division of Nephrology, University of Mississippi Medical Center, Jackson, MS, USA
| | - Surakit Pungpapong
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Mayo Clinic, Jacksonville, FL, USA
| | - Patompong Ungprasert
- 5Clinical Epidemiology Unit, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Magro F, Gionchetti P, Eliakim R, Ardizzone S, Armuzzi A, Barreiro-de Acosta M, Burisch J, Gecse KB, Hart AL, Hindryckx P, Langner C, Limdi JK, Pellino G, Zagórowicz E, Raine T, Harbord M, Rieder F. Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders. J Crohns Colitis 2017; 11:649-670. [PMID: 28158501 DOI: 10.1093/ecco-jcc/jjx008] [Citation(s) in RCA: 1242] [Impact Index Per Article: 155.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2016] [Accepted: 02/01/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Fernando Magro
- Department of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal
| | | | - Rami Eliakim
- Department of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel
| | - Sandro Ardizzone
- Gastrointestinal Unit ASST Fatebenefratelli Sacco-University of Milan-Milan, Italy
| | - Alessandro Armuzzi
- IBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita' Cattolica del Sacro Cuore, Rome, Italy
| | - Manuel Barreiro-de Acosta
- Department of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Krisztina B Gecse
- First Department of Medicine, Semmelweis University, Budapest,Hungary
| | | | - Pieter Hindryckx
- Department of Gastroenterology, University Hospital of Ghent, Ghent, Belgium
| | - Cord Langner
- Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Jimmy K Limdi
- Department of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK
| | - Gianluca Pellino
- Unit of General Surgery, Second University of Naples,Napoli, Italy
| | - Edyta Zagórowicz
- Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland
| | - Tim Raine
- Department of Medicine, University of Cambridge, Cambridge,UK
| | - Marcus Harbord
- Imperial College London; Chelsea and Westminster Hospital, London,UK
| | - Florian Rieder
- Department of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
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Cheung AC, LaRusso NF, Gores GJ, Lazaridis KN. Epigenetics in the Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Semin Liver Dis 2017; 37:159-174. [PMID: 28564724 PMCID: PMC5553635 DOI: 10.1055/s-0037-1603324] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Epigenomics, the study of modifications to genetic material that do not alter the underlying DNA sequence, is generating increasing interest as a means to help clarify disease pathogenesis and outcomes. Although genome-wide association studies have identified several potential candidate genes that may be implicated in primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), it is estimated that these genes explain less than 20% of the heritability of these diseases. Thus, to date, the origins of “missing heritability” for PBC and PSC remain elusive. The epigenome may provide a potentially elegant solution to this phenomenon, as it can be modified by both internal and external exposures (coined the “exposome”). This may explain differences in disease presentation, treatment response, and rates of progression between individuals. Epigenetic changes may also provide a framework for discovering potential biomarkers for diagnosis and screening of PBC and PSC. Importantly, because the epigenome is modifiable, it may also highlight novel pathways for therapeutic discovery and interventions of these diseases.
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Affiliation(s)
- Angela C. Cheung
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Nicholas F. LaRusso
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Gregory J. Gores
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Primary sclerosing cholangitis in the Swiss Inflammatory Bowel Disease Cohort Study: prevalence, risk factors, and long-term follow-up. Eur J Gastroenterol Hepatol 2017; 29:91-97. [PMID: 27622999 DOI: 10.1097/meg.0000000000000747] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIM Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD). We aimed to assess the prevalence of PSC in the Swiss Inflammatory Bowel Disease Cohort Study, to identify associated risk factors, and to describe the long-term evolution. PATIENTS AND METHODS Data of patients enrolled into the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. Logistic regression modeling was performed to identify risk factors for PSC. RESULTS Among 2744 patients [1188 ulcerative colitis (UC); 1556 Crohn's disease (CD)], 57 had PSC (48 UC-PSC, nine CD-PSC). The prevalence of PSC was higher in UC compared with CD (4.04 vs. 0.58%, P<0.001). We identified the following significant independent risk factors for PSC in patients with UC: male sex [odds ratio (OR) 2.771, P=0.022], pancolitis (OR 2.855, P=0.011), nonsmoker at diagnosis (OR 9.253, P=0.030), and a history of appendicectomy (OR 4.114, P=0.019). During a median follow-up time of 74.8 months, four (7.0%) of PSC patients developed cholangiocarcinoma, six (10.5%) underwent liver transplantation, and five (8.8%) died. Survival of IBD-PSC patients was significantly worse compared with IBD patients without PSC (P=0.001). UC-PSC patients developed significantly more frequently colorectal cancer compared with UC patients without PSC (2/48 vs. 9/1440, P=0.017). CONCLUSION Approximately 4% of UC patients and 0.6% of CD patients had PSC. Male sex, pancolitis, nonsmoker status, and a history of appendicectomy were significantly associated with PSC. PSC is associated with considerable morbidity and mortality in the long term.
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Raghu Subramanian C, Triadafilopoulos G. Care of inflammatory bowel disease patients in remission. Gastroenterol Rep (Oxf) 2016; 4:261-271. [PMID: 27899522 PMCID: PMC5193066 DOI: 10.1093/gastro/gow032] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2016] [Revised: 08/21/2016] [Accepted: 09/04/2016] [Indexed: 12/11/2022] Open
Abstract
Inflammatory bowel disease (IBD) comprises two distinct conditions: ulcerative colitis and Crohn’s disease, both of which are chronic, relapsing disorders carrying significant morbidity, mortality and healthcare costs. With growing attention to coordinated healthcare for patients with chronic systemic diseases, this review focuses on the care of IBD patients in remission, their concerns, quality of life, follow-up, the role of primary care physicians and the IBD-specific aspects of long-term care. We did an extensive PubMed search for articles pertaining to IBD patients in remission and, along with the authors’ experience, formulated a comprehensive review. The difficulties faced by IBD patients in remission include but are not limited to education and employment concerns, psychosocial issues, problems related to health insurance, nutrition, fertility and infections. This review also addresses newer treatment modalities, the debatable effects of smoking on IBD and the importance of vaccination. IBD in remission can be a challenge due to its multifaceted nature; however, with a coordinated approach by gastroenterologists and other involved practitioners, several of these issues can be addressed.
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Ribaldone DG, Garavagno M, Pellicano R, Bresso F, Fagoonee S, David E, Sapone N, Bonagura AG, Resegotti A, Astegiano M. Prevalence and prognostic value of hepatic histological alterations in patients with Crohn's disease. Scand J Gastroenterol 2016; 50:1463-8. [PMID: 26133749 DOI: 10.3109/00365521.2015.1064995] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
UNLABELLED Variable degrees of liver histological changes in patients with Crohn's disease (CD) have been reported. OBJECTIVE To evaluate the liver histological alterations and their prognostic significance in patients affected by CD without abnormalities of liver biochemical parameters and ultrasound features. MATERIAL AND METHODS A prospective, single-blind study, including 35 consecutive patients with CD that underwent bowel resection with a contemporary performance of liver biopsy from 1992 to 2003. EXCLUSION CRITERIA the presence of standard causes of liver disease, such as alcohol consumption exceeding 20 g/day, primary sclerosing cholangitis, viral infections, celiac disease, metabolic syndrome and alterations of the metabolism. Patients were followed up with regular evaluation of hepatic cytolysis, cholestasis, synthesis and ultrasound performance. After a mean interval of 14 years (from May to December 2013), liver fibrosis was assessed by Fibroscan®. RESULTS Histological alterations were shown in 60% of patients, without serious liver injuries (no case of inflammation or significant fibrosis). Fibroscan® was performed in 33 subjects and no significant changes were observed (mean value of liver stiffness: 5.2 ± 1.2 kPa). The minimal microscopic damage did not evolve either in patients with a normal histology or in those with an altered histology at baseline (p = 0.9). Only patients who took azathioprine had a statistically significant increase of liver stiffness values (5.7 ± 1.5 kPa vs 4.7 ± 1.3 kPa, p = 0.017). CONCLUSIONS Patients with CD do not need additional examinations compared to the general population, unless clinical or biochemical abnormalities are found.
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Affiliation(s)
- Davide Giuseppe Ribaldone
- Department of Gastroenterology and Hepatology, Città della Salute e della Scienza-Molinette Hospital , Turin , Italy
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Perricone C, Versini M, Ben-Ami D, Gertel S, Watad A, Segel MJ, Ceccarelli F, Conti F, Cantarini L, Bogdanos DP, Antonelli A, Amital H, Valesini G, Shoenfeld Y. Smoke and autoimmunity: The fire behind the disease. Autoimmun Rev 2016; 15:354-74. [DOI: 10.1016/j.autrev.2016.01.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2015] [Accepted: 12/31/2015] [Indexed: 12/14/2022]
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Environmental Risk Factors of Pediatric-Onset Primary Sclerosing Cholangitis and Autoimmune Hepatitis. J Pediatr Gastroenterol Nutr 2016; 62:437-42. [PMID: 26465796 DOI: 10.1097/mpg.0000000000000995] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
OBJECTIVES The aim of this population-based observational case-control questionnaire study was to investigate the possible role of environmental risk factors associated with pediatric-onset autoimmune liver diseases. METHODS Seventy-one patients with autoimmune liver diseases (<16 years) received a questionnaire with 22 items, evaluating contact with environmental factors (eg, family manners, type of housing, pets) before the diagnosis. Two age- and sex-matched control groups were used: inflammatory bowel disease (IBD; n = 91) and healthy subjects (n = 716; matched also for place of residence at birth). Univariate analysis (odds ratio [OR] and 95% confidence interval) for all variables was calculated. Fisher exact test was performed to depict associations between variables and the multivariate logistic regression to test their interactions. RESULTS In the final analyses, the responses of 51 autoimmune liver diseases cases (n = 51/71, 72%), 59 IBD controls (n = 59/91, 65%), and 292 healthy controls (n = 292/716, 41%) were investigated. In univariate analysis only having a cat, a dog, and a cat or a dog were risk factors of autoimmune liver diseases (OR varying between 2.6-3.4); no other significant associations (eg, place of residence, number of siblings, family manners) were found. Multivariate logistic regression analyses showed that especially living with a cat in block of flats was a risk factor (OR 3.6, 1.2-10.8). CONCLUSIONS Living in a close contact with a pet (especially a cat) was a risk factor of autoimmune liver diseases. This finding may suggest an involvement of an unidentified agent (ie, toxin/microbe) among the triggers of these diseases.
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Boonstra K, de Vries EMG, van Geloven N, van Erpecum KJ, Spanier M, Poen AC, van Nieuwkerk CM, Witteman BJ, Tuynman HA, Naber AH, Kingma PJ, Beuers U, Ponsioen CY. Risk factors for primary sclerosing cholangitis. Liver Int 2016; 36:84-91. [PMID: 26077553 DOI: 10.1111/liv.12894] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Accepted: 06/09/2015] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is a progressive cholestatic liver disease of unknown cause, but strongly associated with inflammatory bowel disease (IBD). Potential risk factors triggering PSC have never been studied on a population level. The aim of this study was to evaluate smoking, appendectomy, family history and geographical distribution in a population-based cohort of PSC patients, as compared to IBD control patients and healthy controls (HC). METHODS For this case-control study 343 PSC patients, 370 IBD controls and 232 HC's living in a geographically defined area in the Netherlands filled-out a questionnaire concerning smoking, appendectomy and family history of IBD and autoimmune liver diseases. RESULTS Smoking was associated with a lower risk of developing PSC in PSC-ulcerative colitis (UC) patients (adjusted OR 0.21; 95% CI 0.12-0.34; P < 0.001). Comparable results were found for PSC-Crohn's disease (CD) patients (16% former smokers) compared to CD patients (55% former smokers) (adjusted OR 0.17; 95% CI 0.08-0.39; P < 0.001). Frequency of appendectomy did not differ between PSC and HC, but PSC-UC patients had undergone appendectomy more often than UC patients (13% vs. 6%) (adjusted OR 2.51; 95%CI 1.04-6.07; P = 0.041). We found no association between family history of IBD or autoimmune liver disease and risk of PSC. Degree of urbanization was not associated with PSC incidence. CONCLUSION In this large population-based case-control study we confirm that smoking is associated with a lower risk of developing PSC, independent of its protective effect for developing UC. Appendectomy is not associated with the risk of developing PSC.
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Affiliation(s)
- Kirsten Boonstra
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Elisabeth M G de Vries
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Nan van Geloven
- Clinical Research Unit, Academic Medical Center, Amsterdam, the Netherlands
| | - Karel J van Erpecum
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Marcel Spanier
- Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, the Netherlands
| | - Alexander C Poen
- Department of Gastroenterology and Hepatology, Isala Clinics, Zwolle, the Netherlands
| | - Carin M van Nieuwkerk
- Department of Gastroenterology and Hepatology, VU Medical Center, Amsterdam, the Netherlands
| | - Ben J Witteman
- Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, the Netherlands
| | - Hans A Tuynman
- Department of Gastroenterology and Hepatology, Medical Center Alkmaar, Alkmaar, the Netherlands
| | - Anton H Naber
- Department of Gastroenterology and Hepatology, Tergooiziekenhuizen, Hilversum/Blaricum, the Netherlands
| | - Paul J Kingma
- Department of Gastroenterology and Hepatology, Tergooiziekenhuizen, Hilversum/Blaricum, the Netherlands
| | - Ulrich Beuers
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
| | - Cyriel Y Ponsioen
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, the Netherlands
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Biedermann L, Fournier N, Misselwitz B, Frei P, Zeitz J, Manser CN, Pittet V, Juillerat P, von Känel R, Fried M, Vavricka SR, Rogler G. High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation--Data from the Swiss IBD Cohort Study. J Crohns Colitis 2015; 9:819-29. [PMID: 26116554 DOI: 10.1093/ecco-jcc/jjv113] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 06/08/2015] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Smoking is a crucial environmental factor in inflammatory bowel disease [IBD]. However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS Prospectively obtained data from patients participating in the Swiss IBD Cohort Study was analysed and compared with the general Swiss population [GSP] matched by age, sex and year. RESULTS Among a total of 1770 IBD patients analysed [49.1% male], 29% are current smokers. More than twice as many patients with Crohn's disease [CD] are active smokers compared with ulcerative colitis [UC] [UC, 39.6% vs CD 15.3%, p < 0.001]. In striking contrast to the GSP, significantly more women than men with CD smoke [42.8% vs 35.8%, p = 0.025], with also an overall significantly increased smoking rate compared with the GSP in women but not men. The vast majority of smoking IBD patients [90.5%] claim to never have received any support to achieve smoking cessation, significantly more in UC compared with CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared with non-smokers, but does not differ in UC. CONCLUSIONS Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared with the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.
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Affiliation(s)
- Luc Biedermann
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Nicolas Fournier
- Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
| | - Benjamin Misselwitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Pascal Frei
- Division of Gastroenterology & Hepatology, Seespital Horgen, Horgen, Switzerland
| | - Jonas Zeitz
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Christine N Manser
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Valerie Pittet
- Institute of Social and Preventive Medicine, University of Lausanne, Lausanne, Switzerland
| | - Pascal Juillerat
- Division of Gastroenterology & Hepatology, Inselspital Bern, Bern, Switzerland
| | - Roland von Känel
- Department of Psychosomatic Medicine, Clinic Barmelweid, Barmelweid, Switzerland
| | - Michael Fried
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Stephan R Vavricka
- Division of Gastroenterology & Hepatology, Triemli Hospital, Zurich, Switzerland
| | - Gerhard Rogler
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
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Assis DN, Levy C. Editorial: environmental risk factors for PSC with and without IBD--the story unfolds. Aliment Pharmacol Ther 2015; 41:1214-6. [PMID: 25939466 DOI: 10.1111/apt.13186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- D N Assis
- Medicine - Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA
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Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder that ultimately can lead to cirrhosis, liver failure, malignancy and death. It is strongly associated with inflammatory bowel disease (IBD), and though a rare disease, its incidence is increasing. There are no proven medical therapies for PSC. SOURCES OF DATA Ovid Medline was utilised to search for articles with keywords 'sclerosing cholangitis' and 'cholangiocarcinoma' and containing titles 'primary sclerosing cholangitis', and references of these papers were cross-referenced for further relevant manuscripts. AREAS OF AGREEMENT PSC is a rare disease, and there is a strong association with risk loci within the major histocompatibility complex and other genes common to other autoimmune diseases. PSC is a premalignant condition, associated with higher rates of hepatobiliary and colorectal cancer in patients with ulcerative colitis (UC). AREAS OF CONTROVERSY The pathogenesis is unclear, and competing theories exist surrounding toxic bile acids, enhanced homing of particular T cells from the gut to the liver and increased passage of toxins to the liver through a permeable bowel wall. It is unclear whether the higher rate of colonic cancer in PSC/UC occurs in PSC/Crohn's disease. Ursodeoxycholic acid therapy reduces liver enzymes but has not been shown to improve survival. It may reduce the prevalence of bowel cancer. GROWING POINTS Recent genetic studies have revealed new risk loci, pointing to the importance of the immune system and its interaction with the biome. AREAS TIMELY FOR DEVELOPING RESEARCH On the basis of the genetic studies discussed earlier, novel agents are being developed and trialled in the treatment of PSC.
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Affiliation(s)
- Kate D Williamson
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - Roger W Chapman
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
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20
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Eaton JE, Juran BD, Atkinson EJ, Schlicht EM, Xie X, de Andrade M, Lammert CS, Luketic VA, Odin JA, Koteish AA, Kowdley KV, Chopra KB, Hirschfield GM, Chalasani NP, Lazaridis KN. A comprehensive assessment of environmental exposures among 1000 North American patients with primary sclerosing cholangitis, with and without inflammatory bowel disease. Aliment Pharmacol Ther 2015; 41:980-90. [PMID: 25783671 PMCID: PMC4402146 DOI: 10.1111/apt.13154] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2014] [Revised: 12/13/2014] [Accepted: 02/14/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND The relationships between primary sclerosing cholangitis (PSC) and the environment are largely unknown. AIM To validate associations reported in previous studies and to identify novel environmental exposures among PSC patients. METHODS We performed a multicenter, case-control analysis utilising self-administered questionnaires. Responses between cases (n = 1000) and controls (n = 663) were compared using multivariable logistic regression adjusted for age and gender. The model was further stratified based on inflammatory bowel disease (IBD) status (with IBD n = 741 without IBD n = 259). RESULTS Smoking was associated with PSC only when IBD was present (OR, 0.5; 95% CI 0.4-0.7) but not among those PSC patients without IBD (OR, 0.9; 95% CI 0.7-1.2). Compared to controls, women with PSC (irrespective of the presence of IBD) were less likely to have received hormone replacement therapy (HRT; OR, 0.5; 95% CI 0.4-0.7) and were more likely to have recurrent urinary tract infections (OR, 1.6; 95% CI 1.2-2.3). PSC patients regardless of gender or IBD status were less likely to eat fish (OR, 0.4; 95% CI 0.3-0.6) and grilled/barbecued meat (OR, 0.8; 95% CI 0.7-0.9). In contrast, PSC patients with and without IBD were more likely to consume steak/burgers that were more well done (OR, 1.3; 95% CI 1.2-1.5). CONCLUSIONS IBD (rather than PSC) is associated with smoking. Women with PSC are more likely to have recurrent urinary tract infections and less likely to receive HRT. Dietary intake and methods of food preparation differ in PSC patients when compared to controls.
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Affiliation(s)
- J. E. Eaton
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - B. D. Juran
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - E. J. Atkinson
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - E. M. Schlicht
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
| | - X. Xie
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - M. de Andrade
- Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA
| | - C. S. Lammert
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - V. A. Luketic
- Gastroenterology and Hepatology Section, Virginia Commonwealth University, Richmond, VA, USA
| | - J. A. Odin
- Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA
| | - A. A. Koteish
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - K. V. Kowdley
- Liver Care Network, Swedish Medical Center, Seattle, WA, USA
| | - K. B. Chopra
- Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh, Pittsburgh, PA, USA
| | - G. M. Hirschfield
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Birmingham, UK
| | - N. P. Chalasani
- Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
| | - K. N. Lazaridis
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN, USA
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Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, Mantzaris G, Reinisch W, Colombel JF, Vermeire S, Travis S, Lindsay JO, van Assche G. [Second European evidence-based Consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis (Spanish version)]. REVISTA DE GASTROENTEROLOGÍA DE MÉXICO 2014; 79:263-89. [PMID: 25487134 DOI: 10.1016/j.rgmx.2014.10.001] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 02/07/2023]
Affiliation(s)
- A Dignass
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo.
| | - R Eliakim
- AD y RE contribuyeron de igual manera en este trabajo
| | - F Magro
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - C Maaser
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - Y Chowers
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - K Geboes
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - G Mantzaris
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - W Reinisch
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - J-F Colombel
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - S Vermeire
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - S Travis
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - J O Lindsay
- AD y GVA actuaron como coordinadores del Consenso; AD y RE contribuyeron de igual manera en este trabajo
| | - G van Assche
- AD y GVA actuaron como coordinadores del Consenso.
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Marchioni Beery RM, Vaziri H, Forouhar F. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis: a Review Featuring a Women's Health Perspective. J Clin Transl Hepatol 2014; 2:266-84. [PMID: 26357630 PMCID: PMC4521232 DOI: 10.14218/jcth.2014.00024] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2014] [Revised: 10/15/2014] [Accepted: 10/19/2014] [Indexed: 12/12/2022] Open
Abstract
Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are two major types of chronic cholestatic liver disease. Each disorder has distinguishing features and variable progression, but both may ultimately result in cirrhosis and hepatic failure. The following offers a review of PBC and PSC, beginning with a general overview of disease etiology, pathogenesis, diagnosis, clinical features, natural course, and treatment. In addition to commonly associated manifestations of fatigue, pruritus, and fat-soluble vitamin deficiency, select disease-related topics pertaining to women's health are discussed including metabolic bone disease, hyperlipidemia and cardiovascular risk, and pregnancy-related issues influencing maternal disease course and birth outcomes. This comprehensive review of PBC and PSC highlights some unique clinical considerations in the care of female patients with cholestatic liver disease.
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Affiliation(s)
- Renée M. Marchioni Beery
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
- Correspondence to: Renée M. Marchioni Beery, DO, Division of Internal Medicine, Department of Gastroenterology and Hepatology, 263 Farmington Avenue, Farmington, CT 06030-1845, USA. Tel: +01-860-679-3158, Fax: +01-860-679-3159. E-mail:
| | - Haleh Vaziri
- Division of Internal Medicine, Department of Gastroenterology and Hepatology, University of Connecticut Health Center, Farmington, CT, USA
| | - Faripour Forouhar
- Department of Pathology and Lab Medicine, University of Connecticut Health Center, Farmington, CT, USA
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Lammert C, Juran BD, Schlicht E, Xie X, Atkinson EJ, de Andrade M, Lazaridis KN. Reduced coffee consumption among individuals with primary sclerosing cholangitis but not primary biliary cirrhosis. Clin Gastroenterol Hepatol 2014; 12:1562-8. [PMID: 24440215 PMCID: PMC4101072 DOI: 10.1016/j.cgh.2013.12.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2013] [Revised: 12/27/2013] [Accepted: 12/30/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Coffee consumption has been associated with decreased risk of liver disease and related outcomes. However, coffee drinking has not been investigated among patients with cholestatic autoimmune liver diseases, primary biliary cirrhosis (PBC), or primary sclerosing cholangitis (PSC). We investigated the relationship between coffee consumption and risk of PBC and PSC in a large North American cohort. METHODS Lifetime coffee drinking habits were determined from responses to questionnaires from 606 patients with PBC, 480 with PSC, and 564 healthy volunteers (controls). Patients (those with PBC or PSC) were compared with controls by using the Wilcoxon rank sum test for continuous variables and c(2) method for discrete variables. Logistic regression was used to analyze the estimate of the effects of different coffee parameters (time, frequency, and type of coffee consumption) after adjusting for age, sex, smoking status, and education level. RESULTS Patients with PBC and controls did not differ in coffee parameters. However, 24% of patients with PSC had never drunk coffee compared with 16% of controls (P < .05), and only 67% were current drinkers compared with 77% of controls (P < .05). Patients with PSC also consumed fewer lifetime cups per month (45 vs 47 for controls, P < .05) and spent a smaller percentage of their lifetime drinking coffee (46.6% vs 66.7% for controls, P < .05). These differences remained significant in a multivariate model. Among PSC patients with concurrent ulcerative colitis, coffee protected against proctocolectomy (hazard ratio, 0.34; P < .001). CONCLUSIONS Coffee consumption is lower among patients with PSC, but not PBC, compared with controls.
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Affiliation(s)
- Craig Lammert
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Brian D. Juran
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Erik Schlicht
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Xiao Xie
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Elizabeth J. Atkinson
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Mariza de Andrade
- Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
| | - Konstantinos N. Lazaridis
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. It is a progressive disorder which can ultimately lead to biliary cirrhosis, portal hypertension and hepatic failure. PSC is a complex genetic disorder with male predominance. Environmental predisposing factors include non-smoking. It is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis, which occurs in about two thirds of PSC cases. Recent studies have suggested that PSC-IBD is a separate disease entity from IBD alone with distinctive genetic and phenotypic characteristics. Most PSC patients are asymptomatic at presentation; clinical symptoms include fatigue, jaundice, weight loss, right upper quadrant pain and pruritis. Serum biochemical tests indicate cholestasis, and diagnosis is usually established by cholangiography. In symptomatic patients, median survival from presentation to death or liver transplantation is about 12 years. It is a premalignant condition, and the majority of deaths are from malignancy, particularly cholangiocarcinoma or colonic cancer. PSC has no curative treatment. Medical treatment with ursodeoxycholic acid may slow progression of the disease and reduce colonic dysplasia, though trials lack statistical significance. Liver transplantation is the only option in young patients with PSC and advanced liver disease.
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Andersen IM, Tengesdal G, Lie BA, Boberg KM, Karlsen TH, Hov JR. Effects of coffee consumption, smoking, and hormones on risk for primary sclerosing cholangitis. Clin Gastroenterol Hepatol 2014; 12:1019-28. [PMID: 24076415 DOI: 10.1016/j.cgh.2013.09.024] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2013] [Accepted: 09/06/2013] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about nongenetic risk factors for primary sclerosing cholangitis (PSC), except a possible protective effect of smoking. We investigated the relationship between environmental risk factors and susceptibility to PSC. METHODS A questionnaire was distributed to patients with PSC, recruited from Oslo University Hospital Rikshospitalet in Norway through 2011, and randomly chosen individuals from the Norwegian Bone Marrow Donor Registry (control subjects). Data were analyzed from 240 patients with PSC and 245 control subjects, matched for gender and age. RESULTS A lower proportion of patients with PSC were daily coffee drinkers than control subjects, both currently (76% vs 86%; odds ratio [OR], 0.52; 95% confidence interval [CI], 0.32-0.82; P = .006) and at the age of 18 years (35% vs 49%; OR, 0.58; 95% CI, 0.40-0.83; P = .003). The associations were mainly attributed to differences observed in men. Twenty percent of the patients were ever (current or former) daily smokers compared with 43% of control subjects (OR, 0.33; 95% CI, 0.22-0.50; P < .001). Ever daily smoking before PSC diagnosis was associated with older age at diagnosis (42 years vs 32 years; P < .001). Ever daily smoking (P < .001) and being a coffee drinker at the age of 18 years (P = .048) were independently and negatively associated with PSC. Fewer female patients with PSC than control subjects reported ever use of hormonal contraception (51% vs 85%; P < .001). Among female patients, there was a strong correlation between increasing number of children before the diagnosis of PSC and increasing age at diagnosis (r = 0.63; P < .001). CONCLUSIONS Coffee consumption and smoking might protect against development of PSC. In women, the disease might be influenced by hormonal factors.
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Affiliation(s)
- Ina Marie Andersen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Guro Tengesdal
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Benedicte Alexandra Lie
- Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo
| | - Kirsten Muri Boberg
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo
| | - Tom Hemming Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Division of Gastroenterology, Department of Clinical Medicine, University of Bergen, Bergen, Norway
| | - Johannes Roksund Hov
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo; Section for Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo; K. G. Jebsen Inflammation Research Centre, Research Institute of Internal Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo.
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Zimmer V, Lammert F. Role of genetics in diagnosis and therapy of acquired liver disease. Mol Aspects Med 2014; 37:15-34. [DOI: 10.1016/j.mam.2013.10.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2013] [Revised: 10/07/2013] [Accepted: 10/15/2013] [Indexed: 02/08/2023]
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Risk of diabetes and cardiovascular disease in patients with primary sclerosing cholangitis. J Hepatol 2014; 60:802-8. [PMID: 24291242 DOI: 10.1016/j.jhep.2013.11.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2013] [Revised: 11/15/2013] [Accepted: 11/19/2013] [Indexed: 01/22/2023]
Abstract
BACKGROUND & AIMS Primary sclerosing cholangitis (PSC) is associated with increased mortality. Cardiovascular disease is a leading cause of death in the Western world. We examined the risk of cardiovascular disease and diabetes (type 1 and type 2) in patients with PSC and their first-degree relatives. METHODS This prospective multicentre cohort study included 678 individuals with PSC diagnosed between 1970 and 2004, and 6347 non-PSC reference individuals matched for age, and sex. Through linkage of the Swedish Multigeneration Register we identified 3139 first-degree relatives to PSC patients and 30,953 first-degree relatives to the matched comparison cohort. We retrieved data on cardiovascular disease and type 1 and type 2 diabetes (T1D and T2D) from the National Patient Register, and then examined the association with PSC or having a family history of PSC using Poisson regression. RESULTS During 125,127 person-years of follow-up, 203 individuals with PSC had a diagnosis of cardiovascular disease. This corresponded to a 3.34-fold increased relative risk (RR) of cardiovascular disease in individuals with PSC (95% CI=2.86-3.91). The highest risk estimates were seen for diseases of the arteries, veins, and lymphatic vessels while the RR was neutral for ischemic heart disease (0.90) or only slightly elevated for cerebrovascular disease (1.74). Meanwhile, PSC first-degree relatives were at no increased risk of cardiovascular disease (RR=0.87; 95% CI=0.80-0.95). Individuals with PSC (RR=7.95; 95% CI=4.82-13.12), and to some extent also their first-degree relatives (RR=1.73; 95% CI=1.19-2.52) were at increased risk of T1D. Also for T2D were the RR is higher in individuals with PSC (RR=2.54; 95% CI=1.56-4.13) than in PSC first-degree relatives (RR=0.81; 95% CI=0.65-1.02). CONCLUSIONS PSC was associated with T1D, T2D, and non-ischemic cardiovascular disease. In contrast, first-degree relatives to PSC patients were only at a moderately increased risk of T1D, and at no increased risk of either cardiovascular disease or T2D.
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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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Singh S, Talwalkar JA. Primary sclerosing cholangitis: diagnosis, prognosis, and management. Clin Gastroenterol Hepatol 2013; 11:898-907. [PMID: 23454027 PMCID: PMC3692584 DOI: 10.1016/j.cgh.2013.02.016] [Citation(s) in RCA: 68] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2013] [Revised: 02/05/2013] [Accepted: 02/06/2013] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease of the liver of unclear etiology, characterized by chronic inflammation and fibrosis of bile ducts. It primarily affects middle-aged men and is associated with 4-fold increased mortality as compared with an age- and sex-matched population. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10- to 15-year period from the initial diagnosis. In addition, PSC confers a markedly increased risk of hepatobiliary cancer, including cholangiocarcinoma and gallbladder cancer, as compared with the general population, and cancer is the leading cause of mortality in patients with PSC. It is associated with inflammatory bowel disease in 70% of patients and increases the risk of colorectal cancer almost 10-fold. Despite significant research efforts in this field, the pathogenic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. There are no proven medical therapies that alter the natural course of the disease. Thus, liver transplantation is the only available treatment for patients with advanced PSC, with excellent outcomes in this population.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by multifocal strictures of intra and extrahepatic bile ducts. PSC occurs more commonly in men and is often associated with inflammatory bowel disease. At present, there is no effective medical therapy for PSC. Current management of patients with PSC is centered on endoscopic therapy of biliary strictures, management of complications of chronic cholestasis and of progressive liver disease, and close clinical monitoring for development of cholangiocarcinoma, as well as for timely referral for liver transplantation.
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Affiliation(s)
- Claudia O Zein
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, A31, Cleveland, OH 44195, USA.
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Lazaridis KN, Gores GJ. Primary Sclerosing Cholangitis. SHACKELFORD'S SURGERY OF THE ALIMENTARY TRACT 2013:1405-1416. [DOI: 10.1016/b978-1-4377-2206-2.00112-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Lunney PC, Leong RWL. Review article: Ulcerative colitis, smoking and nicotine therapy. Aliment Pharmacol Ther 2012; 36:997-1008. [PMID: 23072629 DOI: 10.1111/apt.12086] [Citation(s) in RCA: 99] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2012] [Revised: 09/06/2012] [Accepted: 09/23/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Smoking is the best-characterised environmental association of ulcerative colitis (UC). Smoking has been observed to exert protective effects on both the development and progression of UC. AIMS To examine the association between UC and smoking, possible pathogenic mechanisms and the potential of nicotine as a therapeutic agent in the treatment of UC. METHODS A literature search was conducted through MEDLINE, using the MeSH search terms 'ulcerative colitis' and 'smoking' or 'nicotine'. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles. RESULTS Ulcerative colitis is less prevalent in smokers. Current smokers with a prior diagnosis of UC are more likely to exhibit milder disease than ex-smokers and nonsmokers. There is conflicting evidence for smokers having reduced rates of hospitalisation, colectomy and need for oral corticosteroids and immunosuppressants to manage their disease. Multiple potential active mediators in smoke may be responsible for these clinical effects, including nicotine and carbon monoxide, but the precise mechanism remains unknown. Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines. Despite this, the high frequency of adverse events limits its clinical significance. CONCLUSIONS Nicotine's application as a therapeutic treatment in ulcerative colitis is limited. Presently, it may be an option considered only in selected cases of acute ulcerative colitis refractory to conventional treatment options. This review also questions whether nicotine is the active component of smoking that modifies risk and inflammation in ulcerative colitis.
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Affiliation(s)
- P C Lunney
- Sydney Medical School, Concord Clinical School, Concord Repatriation General Hospital, The University of Sydney, Sydney, NSW, Australia
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Dignass A, Eliakim R, Magro F, Maaser C, Chowers Y, Geboes K, Mantzaris G, Reinisch W, Colombel JF, Vermeire S, Travis S, Lindsay JO, Van Assche G. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 1: definitions and diagnosis. J Crohns Colitis 2012; 6:965-90. [PMID: 23040452 DOI: 10.1016/j.crohns.2012.09.003] [Citation(s) in RCA: 636] [Impact Index Per Article: 48.9] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2012] [Accepted: 09/03/2012] [Indexed: 12/12/2022]
Affiliation(s)
- Axel Dignass
- Department of Medicine 1, Agaplesion Markus Hospital, Wilhelm-Epstein-Str. 4, D-60431 Frankfurt/Main, Germany.
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Trivedi PJ, Chapman RW. PSC, AIH and overlap syndrome in inflammatory bowel disease. Clin Res Hepatol Gastroenterol 2012; 36:420-36. [PMID: 22306055 DOI: 10.1016/j.clinre.2011.10.007] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2011] [Revised: 10/08/2011] [Accepted: 10/14/2011] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disorder characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include pruritus, fatigue and in advanced cases ascending cholangitis, cirrhosis and end-stage hepatic failure. Patients are at an increased risk of malignancy arising from the bile ducts, gallbladder, liver and colon. The majority (>80%) of Northern European patients with PSC also have inflammatory bowel disease (IBD), usually ulcerative colitis (UC). IBD commonly presents before the onset of PSC, although the opposite can occur and the onset of both conditions can be separated by many years. The colitis associated with PSC is characteristically mild although frequently involves the whole colon. Despite the majority of patients having relatively inactive colonic disease, paradoxically the risk of colorectal malignancy is substantially increased. Patients may also develop dominant, stenotic lesions of the biliary tree which may be difficult to differentiate from cholangiocarcinoma and the coexistence of IBD may influence the development of this complication. Ursodeoxycholic acid may offer a chemoprotective effect against colorectal malignancy and improve liver biochemical indices. Evidence of any beneficial effect on histological progression of hepatobiliary disease is less clear. High doses (∼25-30 mg/kg/d) may be harmful and should be avoided. Autoimmune hepatitis (AIH) is less common in patients with IBD than PSC, however, an association has been observed. A small subgroup may have an overlap syndrome between AIH and PSC and management should be individualised dependant on liver histology, serum immunoglobulin levels, autoantibodies, degree of biochemical cholestasis and cholangiography.
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Affiliation(s)
- P J Trivedi
- Centre for Liver Research and NIHR Biomedical Research Unit, University of Birmingham, Wolfson Drive, Edgbaston, Birmingham, B15 2TT United Kingdom.
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Calabrese E, Yanai H, Shuster D, Rubin DT, Hanauer SB. Low-dose smoking resumption in ex-smokers with refractory ulcerative colitis. J Crohns Colitis 2012; 6:756-62. [PMID: 22398093 DOI: 10.1016/j.crohns.2011.12.010] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Revised: 12/13/2011] [Accepted: 12/13/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Ulcerative colitis (UC) is primarily a disease of non-smokers. Ex-smokers may have a more refractory disease course and anecdotal evidence in non-controlled clinical trials have suggested that smoking resumption, or the administration of nicotine, may ameliorate signs and symptoms of UC in ex-smokers. We report outcomes of ex-smokers with refractory UC who resumed low-dose cigarette smoking. METHODS 17 ex-smokers with refractory UC were identified. Clinical remission was defined as a disease activity index score of 0. RESULTS Two out of 17 patients refused the recommendation to resume smoking. Of the 15 patients who resumed smoking, the mean daily number of cigarettes was 8.6. Fourteen out of those 15 patients who resumed smoking were able to maintain prolonged clinical remission off steroids. One out of the 15 patients failed to improve and required oral steroids. Another patient was compelled to quit smoking since he became addicted. His disease flared after maintaining a prolonged remission of 3 years and he eventually underwent surgery. Three out of these 15 patients switched from cigarettes smoking to nicotine compounds and continued to maintain remission. CONCLUSION Resumption of low dose smoking in a selected group of ex-smokers with refractory UC may ameliorate signs and symptoms. Quality of life, medication side effects, and smoking risk factors should all be considered and discussed with patients. Smokers should be meticulously followed for compliance with "low-dose" regimen and all associated smoking risks.
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Affiliation(s)
- Emma Calabrese
- Section of Gastroenterology, Hepatology and Nutrition, University of Chicago, Chicago, IL 60637, USA.
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36
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Næss S, Shiryaev A, Hov JR, Franke A, Karlsen TH. Genetics in primary sclerosing cholangitis. Clin Res Hepatol Gastroenterol 2012; 36:325-33. [PMID: 22554879 DOI: 10.1016/j.clinre.2012.02.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2012] [Accepted: 02/24/2012] [Indexed: 02/04/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disorder with a progressive course. PSC is strongly associated with inflammatory bowel disease and is often complicated by cholangiocarcinoma development. Etiology and pathogenesis remain obscure, but the diverse clinical manifestation of the disease might, to some extent, indicate different genetic susceptibility in subgroups of patients. In recent years, genome-wide association studies performed in PSC have identified a number of genetic susceptibility loci. In this mini-review, we suggest that the genetic associations established can be grouped according to four pathogenic aspects relating to inflammation, cholangiocyte function, fibrosis and carcinogenesis. Subclassification of PSC patients according to their genetic predisposition could be a valuable tool in future functional and clinical studies.
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Affiliation(s)
- Sigrid Næss
- Norwegian PSC Research Center, Division of Cancer, Surgery and Transplantation, Oslo University Hospital Rikshospitalet, 0027 Oslo, Norway
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Hagström H, Stål P, Stokkeland K, Bergquist A. Alcohol consumption in patients with primary sclerosing cholangitis. World J Gastroenterol 2012; 18:3105-11. [PMID: 22791946 PMCID: PMC3386324 DOI: 10.3748/wjg.v18.i24.3105] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2011] [Revised: 02/20/2012] [Accepted: 02/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the alcohol drinking patterns in a cohort of primary sclerosing cholangitis (PSC) patients and the possible influence on the development of fibrosis.
METHODS: Ninety-six patients with PSC were evaluated with a validated questionnaire about a patient’s lifetime drinking habits: the lifetime drinking history (LDH) questionnaire. In addition, clinical status, transient elastography and biochemistry values were analysed and registered. Patients were defined as having either significant or non-significant fibrosis. Significant fibrosis was defined as either an elastography value of ≥ 17.3 kPa or the presence of clinical signs of cirrhosis. Patients were divided into two groups depending on their alcohol consumption patterns; no/low alcohol consumption (one drink or unit/d) and moderate/high alcohol consumption (≥ 1 drink or unit/d). LDH data were calculated to estimate lifetime alcohol intake (LAI), current alcohol intake, drinks per year before and after diagnosis of PSC. We also calculated the number of episodes of binge-drinking (defined as consuming ≥ 5 drinks per occasion) in total, before and after the diagnosis of PSC.
RESULTS: The mean LAI was 3882 units of alcohol, giving a mean intake after onset of alcohol consumption of 2.6 units per week. Only 9% of patients consumed alcohol equal to or more than one unit per day. Current alcohol intake in patients with significant fibrosis (n = 26) was less than in patients without significant fibrosis (n = 70), as shown by lower values of phosphatidylethanol (B-PEth) (0.1 μmol/L vs 0.33 μmol/L, respectively, P = 0.002) and carbohydrate-deficient transferrin (CDT) (0.88% vs 1.06%, respectively, P = 0.02). Self-reported LAI was similar between the two groups. Patients with significant fibrosis reduced their alcohol intake after diagnosis from 103 to 88 units per year whereas patients without fibrosis increased their alcohol intake after PSC diagnosis from 111 to 151 units/year. There were no correlations between elastography values and intake of alcohol (units/year) (r = -0.036).
CONCLUSION: PSC patients have low alcohol consumption. The lack of correlation between fibrosis and alcohol intake indicates that a low alcohol intake is safe in these patients.
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Abstract
Cholestasis develops either from a defect in bile synthesis, impairment in bile secretion, or obstruction to bile flow, and is characterized by an elevated serum alkaline phosphatase and gamma-glutamyltransferase disproportionate to elevation of aminotransferase enzymes. Key elements to the diagnostic workup include visualization of the biliary tree by cholangiography and evaluation of liver histology. The hope is that recent advances in understanding the genetic factors and immune mechanisms involved in the pathogenesis of cholestasis will lead to newer therapeutic interventions in the treatment of these diseases.
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Affiliation(s)
- Asma Siddique
- Department of Gastroenterology, Center for Liver Disease, Digestive Disease Institute, Seattle, WA 98111, USA
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Halliday JS, Djordjevic J, Lust M, Culver EL, Braden B, Travis SPL, Chapman RWG. A unique clinical phenotype of primary sclerosing cholangitis associated with Crohn's disease. J Crohns Colitis 2012; 6:174-181. [PMID: 22325171 DOI: 10.1016/j.crohns.2011.07.015] [Citation(s) in RCA: 60] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Revised: 07/27/2011] [Accepted: 07/27/2011] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS A distinct clinical phenotype has been demonstrated for ulcerative colitis with concomitant primary sclerosing cholangitis (PSC). The course and behaviour of Crohn's disease (CD) with PSC has, in contrast, never been defined. We aimed to define the characteristics of patients with concomitant PSC and CD. METHODS The Oxford PSC and IBD databases were abstracted for: PSC subtype, date of diagnosis, symptom onset, smoking history, Mayo Clinic PSC score and outcomes (hepatic failure, liver transplantation, Montréal CD classification, treatment, cancer and death). Patients with PSC/CD were matched 1:2 to two control groups: one with PSC/UC and one with isolated CD. RESULTS 240 patients with PSC were identified; 32 (13%) with CD, 129 (54%) with co-existing UC, and 79 had PSC without IBD. For PSC/CD vs. CD controls, isolated ileal CD was less common (6% vs. 31%, p=0.03). Smoking was less common in PSC/CD (13% vs. 34%, p=0.045). No difference in the distribution of CD, or treatment required was observed. For PSC/CD vs. PSC/UC controls, more patients with PSC/CD were female (50% vs. 28%, p=0.021). 22% of PSC/CD patients had small duct PSC compared with 6% with PSC/UC, (p=0.038). Major event-free survival was prolonged in the PSC/CD group compared with PSC/UC, (Cox regression p=0.04). CONCLUSION Unlike PSC/UC, patients with PSC/CD were as likely to be female as male, more commonly had small duct PSC and less commonly progressed to cancer, liver transplantation, or death. Compared to patients with isolated CD, patients with PSC/CD were less likely to smoke or have ileal disease.
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Affiliation(s)
- J S Halliday
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Oxford, UK.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic inflammatory liver disease characterized by the destruction of medium- to large-sized bile ducts and intense concentric fibrosis. Complications from PSC include bacterial cholangitis, cirrhosis, and cholangiocarcinoma and a therapy that might alter the natural history of the disease remains lacking. Our understanding of the pathogenesis of PSC also remains rudimentary but the strong association between PSC and inflammatory bowel disease suggest causal links between the diseases. The male predominance in PSC, lack of a defined, pathogenic auto-antigen, and the potential role of the innate immune system suggest that PSC may be due to dysregulation of immunity rather than a classic autoimmune disease. However, PSC shares several genetic susceptibility loci with other autoimmune diseases including the human leukocyte antigen DRB01*03 haplotype. The precise immune response of PSC is largely unknown but likely involves activation of the innate immune system by bacterial components delivered to the liver via the portal vein. Induction of adhesion molecules and chemokines leads to the recruitment of intestinal lymphocytes. Bile duct injury results from the sustained inflammation and production of inflammatory cytokines. Biliary strictures may cause further damage as a result of bile stasis and recurrent secondary bacterial cholangitis. Progress in our basic understanding of PSC is desperately needed in order to rationally design new therapeutic approaches to this disease.
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Affiliation(s)
- Christopher L Bowlus
- Division of Gastroenterology and Hepatology, University of California Davis Medical Center, Sacramento, USA.
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Nguyen DL, LaRusso NF, Lazaridis KN. Primary sclerosing cholangitis. BLUMGART'S SURGERY OF THE LIVER, PANCREAS AND BILIARY TRACT 2012:603-614.e3. [DOI: 10.1016/b978-1-4377-1454-8.00041-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Increased risk of colorectal cancer and dysplasia in patients with Crohn's colitis and primary sclerosing cholangitis. Dis Colon Rectum 2011; 54:1392-7. [PMID: 21979184 DOI: 10.1097/dcr.0b013e31822bbcc1] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Almost 10% of all patients with primary sclerosing cholangitis receive a diagnosis of Crohn's disease. Clinical characteristics and the risk of colon cancer or dysplasia in Crohn's disease and primary sclerosing cholangitis are less well examined than in ulcerative colitis. OBJECTIVE This study aimed to describe the clinical characteristics and risk of colorectal dysplasia and cancer in Crohn's disease in patients with primary sclerosing cholangitis. DESIGN This is a cohort study of all patients diagnosed with primary sclerosing cholangitis and colorectal Crohn's disease at Karolinska University Hospital, Huddinge, 1978 to 2006. Each patient was matched for age and the onset of Crohn's disease to 2 controls with colorectal Crohn's disease without liver disease. SETTING This study was conducted at a tertiary referral center. PATIENTS Twenty-eight patients (61% male) with primary sclerosing cholangitis and Crohn's disease and 46 patients (50% male) with Crohn's disease alone were studied. Clinical and endoscopic data were retrieved from medical records. Colonic biopsies from patients with primary sclerosing cholangitis were re-reviewed. MAIN OUTCOME MEASURES The primary outcome measured was the proportion of patients developing colorectal cancer. RESULTS Colorectal cancer or dysplasia developed in 9 patients with primary sclerosing cholangitis and in 3 controls. Patients with primary sclerosing cholangitis were more likely to develop colorectal dysplasia or cancer than controls (OR 6.78; 95% CI (1.65-27.9); P = .016). In patients with primary sclerosing cholangitis compared with controls, perianal fistulas occurred in 3% vs 33% (P = .003), bowel strictures occurred in 7% vs 30% (P = .03), and bowel surgery was performed in 18% vs 46% (P = .01). Histological granulomas were seen in 29% of the patients with primary sclerosing cholangitis compared with 43% in controls (P = not significant). LIMITATIONS This study was limited by its retrospective nature and the limited cohort. CONCLUSIONS Primary sclerosing cholangitis is a risk factor for the development of colorectal cancer and dysplasia in Crohn's disease. Obstructing disease and perianal fistulas are rare in primary sclerosing cholangitis and less common than in colonic Crohn's disease without liver disease.
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Toy E, Balasubramanian S, Selmi C, Li CS, Bowlus CL. The prevalence, incidence and natural history of primary sclerosing cholangitis in an ethnically diverse population. BMC Gastroenterol 2011; 11:83. [PMID: 21767410 PMCID: PMC3160402 DOI: 10.1186/1471-230x-11-83] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2011] [Accepted: 07/18/2011] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic liver disease often associated with inflammatory bowel diseases (IBD). Current epidemiological data are limited to studies of predominantly Caucasian populations. Our aim was to define the epidemiology of PSC in a large, ethnically diverse US population. METHODS The Northern California Kaiser Permanente (KP) database includes records from over 3 million people and was searched for cases of PSC between January 2000 and October 2006. All identified charts were reviewed for diagnosis confirmation, IBD co-morbidity, and major natural history endpoints. RESULTS We identified 169 (101 males) cases fulfilling PSC diagnostic criteria with a mean age at diagnosis of 44 years (range 11-81). The age-adjusted point prevalence was 4.15 per 100,000 on December 31, 2005. The age-adjusted incidence per 100,000 person-years was not significantly greater in men 0.45 (95% CI 0.33-0.61) than women 0.37 (95% CI 0.26-0.51). IBD was present in 109/169 (64.5%) cases and was significantly more frequent in men than women with PSC (73.3% and 51.5%, respectively, p = 0.005). The cumulative average yearly mortality rate was 1.9%. Age and serum sodium, creatinine and bilirubin at diagnosis and albumin at last entry were identified as significant factors associated with death, liver transplant or cholangiocarcinoma. CONCLUSIONS The incidence and prevalence of PSC observed in a representative Northern California population are lower compared to previous studies in Caucasian populations and this might reflect differences in the incidence of PSC among various ethnic groups.
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Affiliation(s)
- Elaine Toy
- Department of Medicine, University of California Davis Medical Center, Sacramento, CA, USA
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Bastida G, Beltrán B. Ulcerative colitis in smokers, non-smokers and ex-smokers. World J Gastroenterol 2011; 17:2740-7. [PMID: 21734782 PMCID: PMC3122262 DOI: 10.3748/wjg.v17.i22.2740] [Citation(s) in RCA: 88] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2010] [Revised: 11/16/2010] [Accepted: 11/23/2010] [Indexed: 02/06/2023] Open
Abstract
Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.
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Karlsen TH, Schrumpf E, Boberg KM. Primary sclerosing cholangitis. Best Pract Res Clin Gastroenterol 2010; 24:655-66. [PMID: 20955968 DOI: 10.1016/j.bpg.2010.07.005] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2010] [Revised: 07/15/2010] [Accepted: 07/16/2010] [Indexed: 01/31/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Clinic for Specialized Medicine and Surgery, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway.
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Knight C, Murray KF. Hepatobiliary associations with inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2009; 3:681-91. [PMID: 19929587 DOI: 10.1586/egh.09.53] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Hepatobiliary disease is not uncommon in patients with inflammatory bowel disease (IBD). The most common autoimmune hepatic associations are primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH). The immunosuppressant medications used in the treatment of IBD also have potential hepatotoxicity. PSC is most commonly associated with IBD, specifically ulcerative colitis. AIH, a more classic autoimmune disease diagnosed commonly in isolation of other conditions in the same individual, is less commonly associated with IBD. Additionally, a subgroup of patients have features of both PSC and AIH, termed overlap syndrome, that is also sometimes seen in IBD patients. This review will discuss the most common liver disease associations seen in patients with IBD: PSC, AIH and overlap syndrome. Additionally, the most common drug-related hepatotoxicities encountered when treating IBD will be reviewed.
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Affiliation(s)
- Crystal Knight
- Seattle Children's and University of Washington School of Medicine, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, 4800 Sand Point Way, NE, PO Box 5371/W-7830, Seattle, WA 98105, USA.
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van der Heide F, Dijkstra A, Weersma RK, Albersnagel FA, van der Logt EMJ, Faber KN, Sluiter WJ, Kleibeuker JH, Dijkstra G. Effects of active and passive smoking on disease course of Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2009; 15:1199-207. [PMID: 19170191 DOI: 10.1002/ibd.20884] [Citation(s) in RCA: 117] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Smoking is a remarkable risk factor for inflammatory bowel disease (IBD), aggravating Crohn's disease (CD) while having beneficial effects on ulcerative colitis (UC). We studied the effects of active and passive smoking in Dutch IBD patients. METHODS A questionnaire focusing on cigarette smoke exposure was sent to 820 IBD patients. Returned questionnaires were incorporated into a retrospective chart review, containing details about disease behavior and received therapy. RESULTS In all, 675 IBD patients (380 [56%] CD and 295 [44%] UC) responded. At diagnosis there were 52% smokers in CD, 41% in the general population, and 28% in UC. The number of present smokers in CD is lower than in the general population (26% versus 35%). No detrimental effects of active smoking on CD were observed, but passive smokers needed immunosuppressants and infliximab more frequently than nonpassive smokers. Active smoking had beneficial effects on UC, indicated by reduced rates of colectomy, primary sclerosing cholangitis, and backwash-ileitis in active smokers compared to never smokers, and higher daily cigarette dose correlated with less extensive colitis and a lower need for therapy. Furthermore, smoking cessation after diagnosis was detrimental for UC patients, indicated by increased needs for steroids and hospitalizations for patients that stopped smoking after compared to before the diagnosis. CONCLUSIONS Active smoking is a risk factor for CD, but does not affect the outcome; passive smoking is detrimental for the outcome of CD patients. In UC, active smoking shows dose-dependent beneficial effects. Our data suggest that passive smoking is a novel risk factor for CD.
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Affiliation(s)
- Frans van der Heide
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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van der Heide F, Dijkstra G, Porte RJ, Kleibeuker JH, Haagsma EB. Smoking behavior in liver transplant recipients. Liver Transpl 2009; 15:648-55. [PMID: 19479809 DOI: 10.1002/lt.21722] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Long-term morbidity and survival after orthotopic liver transplantation (OLT) are to a large degree determined by cardiovascular disease and cancer. Tobacco use is a well-known risk factor for both. The aim of this study was to examine smoking behavior before and after OLT and to define groups at risk for resuming tobacco use after OLT. In addition, we looked for a relation between smoking and morbidity after OLT. All 401 adult patients with a follow-up of at least 2 years after OLT were included. Data were collected from the charts. A questionnaire about smoking habits at 4 time points before and after OLT was sent to all 326 patients alive, and 301 (92%) patients responded. Both before and after OLT, 53% of patients never used tobacco, and around 17% were active smokers. Of the active smokers during the evaluation for OLT, almost one-third succeeded in cessation, often during the waiting time for OLT. Twelve percent of former smokers restarted smoking, mainly after OLT. Tobacco use was the highest in patients with alcoholic liver disease (52% were active smokers before OLT, and 44% were after OLT) and the lowest in patients with primary sclerosing cholangitis (1.4% were active smokers before OLT). At 10 years, the cumulative rate of malignancies was 12.7% in active smokers versus 2.1% in nonsmokers (P = 0.019). No effect on skin cancer or cardiovascular disease was found. In conclusion, smoking is a serious problem after OLT and increases the risk for malignancy. Prevention programs should focus not only on active smokers but also on former smokers.
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Affiliation(s)
- Frans van der Heide
- Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
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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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Abstract
Smoking is an important environmental factor in inflammatory bowel disease (IBD), having different effects in ulcerative colitis (UC) and Crohn's disease (CD). A recent meta-analysis partially confirmed previous findings that smoking was found to be protective against ulcerative colitis and, after onset of the disease, might improve its course, decreasing the need for colectomy. However, smoking increases the risk of developing CD and worsens its course, increasing the need for steroids, immunosuppressants and re-operations. Smoking cessation aggravates ulcerative colitis and improves CD. Data are however, largely conflictive as well as the potential mechanisms involved in this dual relationship are still unknown. In this review article, the authors review the role of smoking in inflammatory bowel diseases.
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