Weismueller, Tobias J. and Trivedi, Palak J. and Bergquist, Annika and Imam, Mohamad and Lenzen, Henrike and Ponsioen, Cyriel Y. and Holm, Kristian and Gotthardt, Daniel and Faerkkilae, Martti A. and Marschall, Hanns-Ulrich and Thorburn, Douglas and Weersma, Rinse K. and Fevery, Johan and Mueller, Tobias and Chazouilleres, Olivier and Schulze, Kornelius and Lazaridis, Konstantinos N. and Almer, Sven and Pereira, Stephen P. and Levy, Cynthia and Mason, Andrew and Naess, Sigrid and Bowlus, Christopher L. and Floreani, Annarosa and Halilbasic, Emina and Yimam, Kidist K. and Milkiewicz, Piotr and Beuers, Ulrich and Huynh, Dep K. and Pares, Albert and Manser, Christine N. and Dalekos, George N. and Eksteen, Bertus and Invernizzi, Pietro and Berg, Christoph P. and Kirchner, Gabi I. and Sarrazin, Christoph and Zimmer, Vincent and Fabris, Luca and Braun, Felix and Marzioni, Marco and Juran, Brian D. and Said, Karouk and Rupp, Christian and Jokelainen, Kalle and de Valle, Maria Benito and Saffioti, Francesca and Cheung, Angela and Trauner, Michael and Schramm, Christoph and Chapman, Roger W. and Karlsen, Tom H. and Schrumpf, Erik and Strassburg, Christian P. and Manns, Michael P. and Lindor, Keith D. and Hirschfield, Gideon M. and Hansen, Bettina E. and Boberg, Kirsten M. (2017) Patient Age, Sex, and Inflammatory Bowel Disease Phenotype Associate With Course of Primary Sclerosing Cholangitis. GASTROENTEROLOGY, 152 (8). 1975-+. ISSN 0016-5085, 1528-0012
Full text not available from this repository. (Request a copy)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: 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 4150 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 and no IBD (both vs ulcerative colitis) 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 ulcerative colitis had an increased risk of liver disease progression compared with patients with Crohn's disease (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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DOSE URSODEOXYCHOLIC ACID; PRIMARY BILIARY-CIRRHOSIS; GENOME-WIDE ASSOCIATION; POPULATION-BASED COHORT; ULCERATIVE-COLITIS; NATURAL-HISTORY; RISK-FACTORS; CLINICAL PRESENTATION; CROHNS-DISEASE; SINGLE-CENTER; Risk Stratification; Immune-Mediated Liver Disease; Autoimmune Liver Disease; Cholestasis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:10 |
| Last Modified: | 19 Feb 2019 07:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/787 |
Actions (login required)
 |
View Item |
