Lending colour to the black box Insights into the course and burden of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease marked by multifocal bile duct strictures and is strongly associated with inflammatory bowel disease (IBD). The disease runs an unpredictable course with increased risk of developing colorectal and hepatobiliary cancers, frequently culminating in liver transplantation. While its cause remains unclear, no proven medical therapy exists to halt disease progression.
Part I assessed the disease burden of PSC. Although individually rare, cholestatic liver diseases pose a significant epidemiological and economical burden. Dutch registry data revealed that patients lose an average of 11.8 healthy life-years in the first 30 years post-diagnosis, spend 12 hospital days annually, incur average yearly medical costs of €12,169, and experience a 25% work productivity loss. Health-related quality of life is reduced, particularly by IBD symptoms, pruritus, and advanced liver disease, but improves post-transplant.
Part II explored the gut–liver axis. Proctocolectomy with permanent ileostomy was linked to a 60% reduced risk of transplantation or PSC-related death, while colectomy with remnant colon or pouch did not show survival benefit. IBD presence or endoscopic activity showed no direct impact on transplant-free survival, presumably due to persistent microscopic gut inflammation.
Part III evaluated biliary tract interventions. Cholecystectomy showed no significant survival effect and should therefore not be avoided in PSC. Ursodeoxycholic acid (UDCA) use did not improve long-term outcomes, though a possible chemoprotective effect against hepatobiliary malignancy was noted, warranting further study.