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Effects of Primary Sclerosing Cholangitis on Risks of Cancer and Death in People With Inflammatory Bowel Disease, Based on Sex, Race, and Age

  • Palak J. Trivedi
    Correspondence
    Correspondence Address correspondence to: Palak J. Trivedi, BSc (Hons), MBBS, MRCP Gastroenterology (UK), PhD, NIHR Birmingham BRC, Institute of Immunology and Immunotherapy, Centre for Liver and Gastrointestinal Research, 5th Floor IBR Building, University of Birmingham, Birmingham, United Kingdom B15 2TT.
    Affiliations
    National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

    Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom

    Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
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  • Hannah Crothers
    Affiliations
    Department of Informatics, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
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  • Jemma Mytton
    Affiliations
    Department of Informatics, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
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  • Sofie Bosch
    Affiliations
    Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, the Netherlands
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  • Tariq Iqbal
    Affiliations
    National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

    Department of Gastroenterology, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
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  • James Ferguson
    Affiliations
    National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

    Liver Unit, University Hospitals Birmingham National Health Service Foundation Trust Queen Elizabeth, Birmingham, United Kingdom
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  • Gideon M. Hirschfield
    Correspondence
    Gideon Hirschfield, MB BChir, PhD, FRCP, Toronto Centre for Liver Disease, University Health Network and Department of Medicine, University of Toronto, Toronto, Canada.
    Affiliations
    National Institute for Health Research Birmingham Biomedical Research Centre, Centre for Liver and Gastroenterology Research, University of Birmingham, Birmingham, United Kingdom

    Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

    Toronto Centre for Liver Disease, University Health Network and Department of Medicine, University of Toronto, Toronto, Canada
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      Background & Aims

      There are insufficient population-level data on the effects of primary sclerosing cholangitis (PSC) in patients with inflammatory bowel disease (IBD).

      Methods

      We identified incident cases of IBD, with PSC (PSC-IBD) and without, from April 2006 to April 2016 and collected data on outcomes through April 2019. We linked data from national health care registries maintained for all adults in England on hospital attendances, imaging and endoscopic evaluations, surgical procedures, cancer, and deaths. Our primary aim was to quantify the effects of developing PSC in patients with all subtypes of IBD and evaluate its effects on hepatopancreatobiliary disease, IBD-related outcomes, and all-cause mortality, according to sex, race, and age.

      Results

      Over 10 years, we identified 284,560 incident cases of IBD nationwide; of these, 2588 patients developed PSC. In all, we captured 31,587 colectomies, 5608 colorectal cancers (CRCs) 6608 cholecystectomies, and 41,055 patient deaths. Development of PSC was associated with increased risk of death and CRC (hazard ratios [HRs], 3.20 and 2.43, respectively; P < .001) and a lower median age at CRC diagnosis (59 y vs 69 y without PSC; P < .001). Compared to patients with IBD alone, patients with PSC-IBD had a 4-fold higher risk of CRC if they received a diagnosis of IBD at an age younger than 40 years; there was no difference between groups for patients diagnosed with IBD at an age older than 60 years. Development of PSC also increased risks of cholangiocarcinoma (HR, 28.46), hepatocellular carcinoma (HR, 21.00), pancreatic cancer (HR, 5.26), and gallbladder cancer (HR, 9.19) (P < .001 for all). Risk of hepatopancreatobiliary cancer-related death was lower among patients with PSC-IBD who received annual imaging evaluations before their cancer diagnosis, compared to those who did not undergo imaging (HR, 0.43; P = .037). The greatest difference in mortality between the PSC-IBD alone group vs the IBD alone group was for patients younger than 40 years (incidence rate ratio >7), in contrast to those who received a diagnosis of IBD when older than 60 years (incidence rate ratio, <1.5). Among patients with PSC-IBD we observed 173 first liver transplants. Liver transplantation and PSC-related events accounted for approximately 75% of clinical events when patients received a diagnosis of PSC at an age younger than 40 years vs 31% of patients who received a diagnosis when older than 60 years (P < .001). African Caribbean heritage was associated with increased risks of liver transplantation or PSC-related death compared with white race (HR, 2.05; P < .001), whereas female sex was associated with reduced risk (HR, 0.74; P = .025).

      Conclusions

      In a 10-year, nationwide study, we confirmed that patients with PSC-IBD have increased risks of CRC, hepatopancreatobiliary cancers, and death compared to patients with IBD alone. In the PSC-IBD group, diagnosis of IBD at age younger than 40 years was associated with greater risks of CRC and all-cause mortality compared with diagnosis of IBD at older ages. Patients who receive a diagnosis of PSC at an age younger than 40 years, men, and patients of African Caribbean heritage have an increased incidence of PSC-related events.

      Graphical abstract

      Keywords

      Abbreviations used in this paper:

      CCA (cholangiocarcinoma), CD (Crohn’s disease), CRC (colorectal cancer), HCC (hepatocellular carcinoma), HES (Hospital Episode Statistics), HPB (hepatopancreatobiliary), HR (hazard ratio), IBD (inflammatory bowel disease), IBD-U (inflammatory bowel disease–unclassified), ICD (International Statistical Classification of Diseases and Related Health Problems), IQR (interquartile range), IR (incidence rate), IRR (incidence rate ratio), MRCP (magnetic resonance cholangiopancreatography), NHS (National Health Service), PSC (primary sclerosing cholangitis), UC (ulcerative colitis), YLL (years of life lost)
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