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OC-030 Defining the Unmet Need in Primary Sclerosing Cholangitis: The International PSC Group Risk Stratification Study
  1. PJ Trivedi1,
  2. TJ Weismuller2,
  3. A Bergquist3,
  4. GM Hirschfield1,
  5. BE Hansen4,
  6. KM Boberg5,
  7. on behalf of the International Primary Sclerosing Cholangitis Study Group (IPSCSG)
  1. 1National Institute of Health Research (Birmingham) Liver Biomedical Research Unit (BRU), Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
  2. 2Department of Internal Medicine I, University of Bonn, Bonn, Germany
  3. 3Centre for Digestive Diseases, Division of Hepatology, Stockholm, Sweden
  4. 4Department of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, Netherlands
  5. 5Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Abstract

Introduction Primary sclerosing cholangitis (PSC) is a relatively uncommon hepatobiliary disorder associated with inflammatory bowel disease (IBD), wherein therapy other than transplantation remains ineffective. To understand disease course, within a goal of appropriately stratified care, the International PSC Study Group describes the natural history and clinical phenotypes across the largest cohort ever assembled.

Methods We collected individual-patient data from 1980 to 2010 (37 centres, 17 countries) and conducted risk-assessment for commonly recognised phenotypic associations.

Results Of 7,119 patients, 2,622 progressed to liver transplantation/death (LTD) (median 14·2 years) and 722 developed hepatobiliary malignancy (incidence rates: 47·5 and 13·7 per-1,000-patient-years, respectively). Cholangiocarcinoma was the most frequent malignancy (n = 596), with 38·1% of cases identified within 1 year of PSC diagnosis. Observing the patient cohort in entirety, the majority were men (65·5%), had classical/large-duct disease (89·5%), and developed IBD at some point (70·0%).

IBD consistent with Crohn’s disease (vs. ulcerative colitis) or an absence of IBD over time conferred a lower risk of LTD (time-dependent, unadjusted hazard ratio (HR): 0·61, p < 0.001; and HR:0·90, p = 0·03; respectively) and malignancy (unadj. HR:0·68, p = 0·007 and HR:0·77, p = 0·003; respectively), as did small-duct PSC (sdPSC) (unadj. HR:0·50, p < 0·001 and HR:0·40, p < 0·001; for LTD and malignancy, respectively) and female sex (unadj. HR:0·89, p = 0·018 and HR:0·70, p < 0·001; for LTD and malignancy, respectively).

On multivariable analyses assessing LTD, the impact of sdPSC over classical PSC persisted, with greater protection apparent for men (adjusted HR:0·31, p < 0·001) than women (adj. HR:0·56, p = 0·009). However, women with classical PSC expressed a lower independent risk of disease progression than men of matched PSC subtype (adj. HR:0·9, p = 0.022). IBD-phenotype retained independent stratification properties of LTD, with Crohn’s disease and IBD-absence characterising lower-risk subgroups (time-dependent adj. HR:0·69 and HR:0·89, p < 0·001 and p = 0.012; respectively). sdPSC (adj. HR:0·45, p = 0·02), Crohn’s disease (time-dependent adj. HR:0·72, p = 0·045), and IBD-absence (time-dependent adj. HR:0·72, p = 0·02) were also independently predictive of a lower HPB malignancy risk.

Conclusion Using a robust, internationally representative cohort of unique size we demonstrate how distinct, clinically meaningful phenotypes stratify outcomes in PSC. We highlight the great-unmet need for patients, and provide risk markers clinically relevant to patient care and future trial design.

Disclosure of Interest None Declared

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