Hannover Medical Sch, Germany.
Academic Medical Centre, Netherlands.
National Hospital Norway, Norway.
University Hospital Heidelberg, Germany.
University of Helsinki, Finland.
University of Gothenburg, Sweden.
Royal Free Hospital, England.
University of Groningen, Netherlands; University of Medical Centre Groningen, Netherlands.
University Hospital Gasthuisberg, Belgium.
Charite, Germany.
Hop St Antoine, France.
University of Medical Centre Hamburg Eppendorf, Germany.
Mayo Clin, MN USA.
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
UCL, England.
University of Miami, FL USA.
University of Alberta, Canada.
National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
University of Calif Davis, CA 95616 USA.
University of Padua, Italy.
Medical University of Vienna, Austria.
Calif Pacific Medical Centre, CA USA.
Pomeranian Medical University, Poland; Medical University of Warsaw, Poland.
Academic Medical Centre, Netherlands.
Royal Adelaide Hospital, Australia.
University of Barcelona, Spain.
University Hospital Zurich USZ, Switzerland.
University of Thessaly, Greece.
University of Calgary, Canada.
University of Milano Bicocca, Italy.
University of Tubingen, Germany.
University Hospital Regensburg, Germany.
Johann Wolfgang Goethe University Hospital, Germany.
Saarland University, Germany.
University of Padua, Italy.
UKSH, Germany.
University of Politecn Marche, Italy.
Mayo Clin, MN USA.
Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
University Hospital Heidelberg, Germany.
University of Helsinki, Finland.
University of Gothenburg, Sweden.
Royal Free Hospital, England; Royal Free Hospital, England.
Mayo Clin, MN USA; University of Helsinki, Finland.
Medical University of Vienna, Austria.
University of Medical Centre Hamburg Eppendorf, Germany; University of Medical Centre Hamburg Eppendorf, Germany.
University of Oxford, England; John Radcliffe Hospital, England.
National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
National Hospital Norway, Norway; National Hospital Norway, Norway; University of Oslo, Norway.
University of Bonn, Germany.
Hannover Medical Sch, Germany.
Mayo Clin, MN USA; Mayo Clin, AZ USA; Arizona State University, AZ USA.
University of Birmingham, England.
Erasmus University, Netherlands; University of Toronto, Canada; Toronto Gen Hospital, Canada.
National Hospital Norway, Norway; University of Oslo, Norway.
BACKGROUND amp; 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, Crohns disease and no IBD (both vs ulcerative colitis) were associated with a lower risk of LTD (unadjusted hazard ratio [HR], 0.62; P amp;lt;.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 amp;lt;.001). Female sex was also associated with a lower risk of LTD or malignancy (HR, 0.88; P =.002 and HR, 0.68; P amp;lt;.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 amp;lt;.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 Crohns disease (HR, 1.56; P amp;lt;.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.
W B SAUNDERS CO-ELSEVIER INC , 2017. Vol. 152, no 8, p. 1975-+
Risk Stratification; Immune-Mediated Liver Disease; Autoimmune Liver Disease; Cholestasis
Funding Agencies|German Federal Ministry of Education and Research through the Integrated Research and Treatment Center Transplantation at Hannover Medical School [01EO0802]; Wellcome Trust; NIHR Birmingham Biomedical Research Centre (BRC); NIHR University College London Hospitals Biomedical Research Centre; NIH [R01 DK84960]; German Research Community [MU 2864/1-1, MU 2864/1-3]; German Research Community (DFG) [SFB 841]; YAEL-Foundation; Helmut and Hannelore Greve Foundation