Are we ready to change our surveillance strategy for primary sclerosing cholangitis patients?

The variability in the course of primary sclerosing cholangitis (PSC) is well known, with recognized long-term complications of advanced fibrosis, secondary biliary cirrhosis, and recurrent bacterial cholangitis, as well as an increased risk of hepatobiliary malignancy. Endoscopic retrograde cholangiopancreatography (ERCP) has a pivotal role in selected patients with PSC for two main indications: (i) detection of cholangiocarcinoma by brush sampling of dominant strictures; and (ii) potential reduction of bacterial cholangitis and/or slowdown of the fibrotic process by the dilation of targetable dominant strictures. Different strategies have been proposed for the selection of at-risk patients to whom ERCP should be offered, with the aim of improving patient prognosis and avoiding unneeded interventions that are potentially associated with complications.

In this issue of Endoscopy, Barner-Rasmussen et al. [1] report an important study that aimed to better define the optimal follow-up strategy for PSC patients. The research compared cohorts from different countries, including 1034 patients from Finland who were exposed to a “scheduled ERCP” strategy, 412 patients from Sweden who were exposed to an “annual magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP)” surveillance strategy, and 201 patients from the Netherlands who were exposed to an “on-demand ERCP” strategy.

“...the Northern (Finnish) scheduled ERCP follow-up strategy would need to be confirmed in terms of its clinical outcome advantages in Central/Southern Europe before becoming established as a standard of care in PSC patients.”

The scheduled ERCP strategy involved the confirmation of PSC by ERCP at the time of suspicion on MRCP, with the interval for follow-up ERCP (from 3 months to 5 years) then based on multiple factors (e.g. severity of the cholangiogram, Helsinki score [2], need for dilation, degree of biliary inflammation assessed by cytology, biliary calprotectin, and IL-8, and the presence of biliary dysplasia [3]). MRCP was performed before each further ERCP.

The annual MRI/MRCP strategy involved clinical follow-up and a contrast-enhanced MRI/MRCP annually. ERCP was offered for high grade or progressive dominant strictures, or symptoms associated with cholestasis or bacterial cholangitis, with the aim of performing brush sampling with fluorescence in situ hybridization (FISH) at the time of stricture dilation.

The on-demand ERCP strategy involved the performance of an MRCP at the time of symptoms/worsening of cholestasis or based on annual ultrasound findings, with ERCP offered in the case of dominant stricture-associated symptoms or assessment to exclude neoplasia.

Comparing these three strategies, the authors demonstrated that the cumulative incidence of the composite end point (i.e. hepatobiliary malignancy, liver transplantation, or liver-related death) was lowest (14.1%, 95%CI 12.0%–16.4%) for the scheduled ERCP strategy and highest with the on-demand ERCP strategy (35.0%, 95%CI 28.4%–42.0%). In addition, the cumulative incidence of cholangiocarcinoma was lowest in the scheduled ERCP group and highest in the on-demand group. The incidence of liver transplantation did not differ between scheduled ERCP and MRI/MRCP surveillance, but was higher in the on-demand ERCP group. The incidence of liver-related death was similar across all cohorts. These data suggest that scheduled ERCP is associated with better outcomes in PSC patients.

However, although these results are potentially very exciting and could change practice in PSC patient management, they should be interpreted with caution. The improved outcome observed through the analysis of the composite end point could be partially related to a lower incidence of cholangiocarcinoma in the cohort from Finland compared with the two other cohorts. It has been shown previously that there is a difference in epidemiology between Northern and Southern Europe, with a higher incidence of PSC in the North and lower incidence of cholangiocarcinoma in Finland compared with the Netherlands [4].

Are there alternative explanations for the results of this recent study from Barner-Rasmussen et al.? Is the scheduled ERCP strategy with stricture dilation, using a personal risk stratification score to define ERCP intervals, associated with reductions in fibrotic progression and the further development of secondary biliary cirrhosis? It appears that the difference in FIB4 from baseline to the end of follow-up was lower in the scheduled ERCP group, suggesting a slower progression of fibrosis compared with the other groups. One might have expected to observe a reduced need for transplantation in the scheduled ERCP group compared with the MRI/MRCP group, but this was not the case, potentially owing to the increased detection of cholangiocarcinoma at the early time of follow-up in the scheduled ERCP group, with the transplantation program in Finland allowing this indication. Again, no reduction in liver-related deaths was observed in the scheduled ERCP group despite lower fibrosis progression scores.

Ideally, the Northern (Finnish) scheduled ERCP follow-up strategy would need to be confirmed in terms of its clinical outcome advantages in Central/Southern Europe before becoming established as a standard of care in PSC patients.

In addition to a better follow-up strategy to offer to PSC patients, this study also highlights the pivotal place of MRCP for dominant stricture detection in these patients [5]. Indeed, MRCP was mainly offered to patients in the scheduled ERCP and annual MRI/MRCP groups, and was much less common in the on-demand ERCP strategy, which was associated with a much worse outcome.

Taken together, despite optimal outcomes in the scheduled ERCP group, the risk of malignancy development and need for liver transplantation still represent significant clinical problems. In addition to improving optimal follow-up strategies, new anti-inflammatory/antifibrotic therapies [6] are crucially needed to further improve PSC patient outcomes.

Publication History

Article published online:
20 February 2025

• References

• 1 Barner-Rasmussen N, Molinaro A, Mol B. et al. Surveillance of primary sclerosing cholangitis – a comparison of scheduled or on-demand ERCP with annual magnetic resonance-based surveillance: a multicenter study. Endoscopy 2025;
• 2 Boyd S, Tenca A, Jokelainen K. et al. Screening primary sclerosing cholangitis and biliary dysplasia with endoscopic retrograde cholangiography and brush cytology: risk factors for biliary neoplasia. Endoscopy 2016; 48: 432-439
• 3 Barner-Rasmussen N, Sjöblom N, Arola J. et al. The role of serology, liver function tests and imaging in screening of primary sclerosing cholangitis: the HelPSCreen score. Scand J Gastroenterol 2023; 58: 1491-1498
• 4 Trivedi PJ, Bowlus CL, Yiman KK. et al. Epidemiology, natural history and outcomes of primary sclerosing cholangitis: a systematic review of populations based studies. Clin Gastroenterol Hepatol 2022; 20: 1687-1700
• 5 Aabakken L, Karlsen T, Albert J. et al. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. Endoscopy 2017; 49: 588-608
• 6 Bhushan S, Sohal A, Kowdley K. Primary biliary cholangitis and primary sclerosing cholangitis therapy landscape. Am J Gastroenterol 2025; 120: 151-158