Understanding hepatopancreatobiliary cancer risks in a population-based primary sclerosing cholangitis-inflammatory bowel disease cohort

Kristel K Leung; Wenbin Li; Bettina Hansen; Aliya Gulamhusein; Lauren Lapointe-Shaw; Amanda Ricciuto; Eric I Benchimol; Jennifer A Flemming; Gideon M Hirschfield

doi:10.1097/HEP.0000000000001692

Understanding hepatopancreatobiliary cancer risks in a population-based primary sclerosing cholangitis-inflammatory bowel disease cohort

Hepatology. 2026 Feb 4. doi: 10.1097/HEP.0000000000001692. Online ahead of print.

Authors

Kristel K Leung^{1

2

3}, Wenbin Li⁴, Bettina Hansen^{1

2

5}, Aliya Gulamhusein¹, Lauren Lapointe-Shaw^{2

6}, Amanda Ricciuto^{7

8}, Eric I Benchimol^{2

6

7

8

9}, Jennifer A Flemming^{3

4}, Gideon M Hirschfield¹

Affiliations

¹ The Autoimmune and Rare Liver Disease Programme, Division of Gastroenterology and Hepatology, Toronto General Hospital, Toronto, Ontario, Canada.
² Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Ontario, Canada.
³ Department of Medicine, Queen's University, Kingston, Ontario, Canada.
⁴ ICES-Queen's, Kingston, Ontario, Canada.
⁵ Department of Biostatistics and Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
⁶ ICES, Toronto, Ontario, Canada.
⁷ SickKids Inflammatory Bowel Disease Centre, Division of Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁸ Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.
⁹ Child Health Evaluative Sciences, SickKids Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

PMID: 41637315
DOI: 10.1097/HEP.0000000000001692

Abstract

Background and aims: Primary sclerosing cholangitis (PSC) is a pre-malignant condition with elevated risk of hepatopancreatobiliary cancers (HPBCa) and colorectal cancer (CRC) when inflammatory bowel disease (IBD) is present. We described cancer burden in a contemporary PSC-IBD cohort, and assessed rates of subsequent cancers, liver transplant, and death post-colectomy or post-cholecystectomy status.

Methods: Using linked health administrative databases, we calculated cause-specific cumulative incidences of HPBCa-related outcomes (diagnoses/deaths) and non-HPBCa-related transplant/death among individuals with PSC-IBD in Ontario, Canada (2002-2018), followed to 2021. Transition probabilities and transition intensity ratios (TIR) were evaluated using a multistate Markov model.

Results: Among 476 individuals with incident PSC-IBD, there was a 54% probability of remaining event-free at 10 years. Approximately 1 in 20 experienced an HPBCa-related outcome, and up to 1 in 4 had a non-HPBCa-related transplant/death. During follow-up, 13% experienced multiple events. Age was associated with HPBCa (HR 1.02, 95% CI 1.01-1.04), but not sex. Mortality occurred more frequently post-colectomy (TIR 3.08, 95% CI 1.7-5.59) and post-cholecystectomy (TIR 3.85, 95% CI 2.21-6.64) relative to event-free PSC-IBD, but there were no differences in post-surgery incidence of cancer or transplant.

Conclusions: While some individuals with PSC-IBD experienced an extended event-free disease course, a large proportion experienced disease-related cancer, colectomy, cholecystectomy, and transplant events. Higher mortality rates observed after surgery were likely related to underlying disease processes that motivated surgical intervention (eg, dysplasia/malignancy, refractory IBD), rather than the surgery itself. Understanding how PSC-IBD disease trajectories vary can inform individual management and patient counselling.

Keywords: cholangiocarcinoma; cholestatic liver disease; colorectal neoplasms; disease progression; prognosis.