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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

Weismüller, Tobias J ; Trivedi, Palak J ; Bergquist, Annika ; Imam, Mohamad ; Lenzen, Henrike ; Ponsioen, Cyriel Y ; Holm, Kristian ; Gotthardt, Daniel ; Färkkilä, Martti A ; Marschall, Hanns- Ulrich ; Thorburn, Douglas ; Weersma, Rinse K ; Fevery, Johan ; Mueller, Tobias ; Chaouillères, Olivier ; Schulze, Kornelius ; Lazaridis, Konstantinos N ; Almer, Sven ; Pereira, Stephen P ; Levy, Cynthia ; Mason, Andrew ; Naess, Sigrid ; Bowlus, Christopher L ; Floreani, Annarosa ; Halilbasic, Emina ; Yimam, Kidist K ; Milkiewicz, Piotr ; Beuers, Ulrich ; Huynh, Dep K ; Pares, Albert ; Manser, Christine N ; Dalekos, George N ; Eksteen, Bertus ; Invernizzi, Pietro ; Berg, Christoph P ; Kirchner, Gabi I ; Sarrazin, Christoph ; Zimmer, Vincent ; Fabris, Luca ; Braun, Felix ; Marzioni, Marco ; Juran, Brian D ; Said, Karouk ; Rupp, Christian ; Jokelainen, Kalle ; Benito de Valle, Maria ; Saffioti, Francesca ; Cheung, Angela ; Trauner, Michael ; Schramm, Christoph ; Chapman, Roger W ; Karlsen, Tom H ; Schrumpf, Erik ; Strassburg, Christian P ; Manns, Michael P ; Lindor, Keith D ; Hirschfield, Gideon M ; Hansen, Bettina E ; Boberg., Kirsten M

Gastroenterology (New York, N.Y. 1943), 2017-06, Vol.152 (8), p.1975-1984.e8 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis
Autor: Weismüller, Tobias J ; Trivedi, Palak J ; Bergquist, Annika ; Imam, Mohamad ; Lenzen, Henrike ; Ponsioen, Cyriel Y ; Holm, Kristian ; Gotthardt, Daniel ; Färkkilä, Martti A ; Marschall, Hanns- Ulrich ; Thorburn, Douglas ; Weersma, Rinse K ; Fevery, Johan ; Mueller, Tobias ; Chaouillères, Olivier ; Schulze, Kornelius ; Lazaridis, Konstantinos N ; Almer, Sven ; Pereira, Stephen P ; Levy, Cynthia ; Mason, Andrew ; Naess, Sigrid ; Bowlus, Christopher L ; Floreani, Annarosa ; Halilbasic, Emina ; Yimam, Kidist K ; Milkiewicz, Piotr ; Beuers, Ulrich ; Huynh, Dep K ; Pares, Albert ; Manser, Christine N ; Dalekos, George N ; Eksteen, Bertus ; Invernizzi, Pietro ; Berg, Christoph P ; Kirchner, Gabi I ; Sarrazin, Christoph ; Zimmer, Vincent ; Fabris, Luca ; Braun, Felix ; Marzioni, Marco ; Juran, Brian D ; Said, Karouk ; Rupp, Christian ; Jokelainen, Kalle ; Benito de Valle, Maria ; Saffioti, Francesca ; Cheung, Angela ; Trauner, Michael ; Schramm, Christoph ; Chapman, Roger W ; Karlsen, Tom H ; Schrumpf, Erik ; Strassburg, Christian P ; Manns, Michael P ; Lindor, Keith D ; Hirschfield, Gideon M ; Hansen, Bettina E ; Boberg., Kirsten M
Assuntos: Adult ; Age Distribution ; association ; Australia - epidemiology ; Autoimmune Liver Disease ; Chi-Square Distribution ; Cholangitis, Sclerosing - diagnosis ; Cholangitis, Sclerosing - epidemiology ; Cholangitis, Sclerosing - mortality ; Cholangitis, Sclerosing - surgery ; Cholestasis ; clinical presentation ; Colitis ulcerosa ; Colitis, Ulcerative - diagnosis ; Colitis, Ulcerative - epidemiology ; Colitis, Ulcerative - mortality ; Colitis, Ulcerative - surgery ; Crohn Disease - diagnosis ; Crohn Disease - epidemiology ; Crohn Disease - mortality ; Crohn Disease - surgery ; crohns-disease ; Disease Progression ; dose ursodeoxycholic acid ; Europe - epidemiology ; Female ; Gastroenterologi ; Gastroenterology & Hepatology ; Gastroenterology and Hepatology ; genome-wide ; Humans ; Immune-Mediated Liver Disease ; Incidence ; Inflamació ; Inflammation ; Kaplan-Meier Estimate ; Liver Transplantation ; Male ; Medicin och hälsovetenskap ; Middle Aged ; Multivariate Analysis ; natural-history ; North America - epidemiology ; Phenotype ; population-based cohort ; primary biliary-cirrhosis ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Risk Stratification ; Sex Distribution ; single-center ; Time Factors ; Ulcerative colitis ; Young Adult
É parte de: Gastroenterology (New York, N.Y. 1943), 2017-06, Vol.152 (8), p.1975-1984.e8
Notas: ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Authors share co-first authorship
Sven Almer’s current affiliation is the Department of Medicine, Karolinska Institutet, Solna, and Center for Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
Authors share co-senior authorship.
Descrição: Abstract Background & Aims Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large, international cohort of patients with PSC. Methods We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Results Of the 7121 patients in the cohort, 2616 met the primary endpoint (median time-to-event of 14.5 years) and 721 developed hepatopancreatobiliary malignancy. The most common malignancy was cholangiocarcinoma (n=594); patients of advanced age at diagnosis had an increased incidence, compared with younger patients (incidence rate [IR]: 1.2 per 100 patient-years for patients younger than 20 years old, 6.0 per 100 patient-years for patients 21–30 years old, 9.0 per 100 patient-years for patients 31–40 years old, 14.0 per 100 patient-years for patients 41–50 years old, 15.2 per 100 patient-years for patients 51–60 years old, and 21.0 per 100 patient-years for patients older than 60 years). Of all patients with PSC studied, 65.5% were men, 89.8% had classical or large-duct disease, and 70.0% developed IBD at some point. Assessing the development of IBD as a time-dependent covariate, Crohn’s disease (CD) and no IBD (both vs ulcerative colitis [UC]) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P <.001 and HR, 0.90; P =.03; respectively) and malignancy (HR, 0.68; P =.008 and HR, 0.77; P =.004, respectively). Small-duct PSC was associated with a lower risk of LTD or malignancy compared with classic PSC (HR, 0.30 and HR, 0.15, respectively; both P <.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P <.001, respectively). In multivariable analyses assessing the primary endpoint, small-duct PSC characterized a low-risk phenotype in both sexes (adjusted HR for men, 0.23; P <.001 and adjusted HR for women, 0.48; P =.003). Conversely, patients with UC had an increased risk of liver disease progression compared to patients with CD (HR, 1.56; P <.001) or no IBD (HR, 1.15; P =.002). Conclusions In an analysis of data from individual patients with PSC worldwide, we found significant variation in clinical course associated with age at diagnosis, sex, and ductal- and IBD subtypes. The survival estimates provided might be used to estimate risk levels for patients with PSC and select patients for clinical trials.
Editor: United States: Elsevier Inc
Idioma: Inglês

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Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis

United States: Elsevier Inc

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