Hepatobiliary Cancer Risk in Patients with Inflammatory Bowel Disease: A Scandinavian Population-Based Cohort Study

Abstract

Background: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among IBD patients. Methods: This Swedish/Danish population-based cohort study (1969-2017) followed IBD patients and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. Results: Among the 97,496 ulcerative colitis patients/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall HRs were 1.83 (95%CI: 1.41-2.38) for HCC-, 7.33 (95%CI: 5.81-9.25) for ICC-, and 4.46 (95%CI: 3.49-5.70) for ECC-death. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among ulcerative colitis patients with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 Crohn's disease patients (median follow-up 11 years), 10-year-mortality from HCC (n=28), ICC (n=28), and ECC (n=24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95%CI: 1.31-2.93), 3.33 (95%CI: 2.19-5.09), and 3.10 (95%CI: 1.97-4.87). 1/28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. Conclusions: Risk of HCC-, ICC-, and ECC-death was low in IBD patients and decreased over time. However, a large proportion of deaths occurred after PSC. Impact: Guidelines on specific surveillance strategies for IBD patients with PSC, but not those without PSC, are needed.