A retrospective evaluation of preemptive liver transplantation for bile duct dysplasia in primary sclerosing cholangitis: Balancing risks and benefits

Sigurd Breder; Christina Villard; Emma Eide; Benny Wang; Lise Katrine Engesæter; Henrik Mikael Reims; Johannes Roksund Hov; Espen Melum; Lars Aabakken; Pål Dag Line; Jon Lømo; Krzyztof Grzyb; Kristine Wiencke; Annika Bergquist; Trine Folseraas

doi:10.1016/j.jhepr.2025.101598

A retrospective evaluation of preemptive liver transplantation for bile duct dysplasia in primary sclerosing cholangitis: Balancing risks and benefits

JHEP Rep. 2025 Sep 20;7(12):101598. doi: 10.1016/j.jhepr.2025.101598. eCollection 2025 Dec.

Authors

Sigurd Breder^{1

2}, Christina Villard^{3

4}, Emma Eide¹, Benny Wang³, Lise Katrine Engesæter^{1

2

5}, Henrik Mikael Reims⁶, Johannes Roksund Hov^{1

2

5

7}, Espen Melum^{1

2

5

7

8}, Lars Aabakken^{1

2

5}, Pål Dag Line^{1

9}, Jon Lømo⁶, Krzyztof Grzyb⁶, Kristine Wiencke⁵, Annika Bergquist^{4

10}, Trine Folseraas^{1

2

5}

Affiliations

¹ Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
² Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
³ Department of Transplantation Surgery, Karolinska University Hospital, Stockholm, Sweden.
⁴ Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
⁵ Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁶ Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁷ Research Institute of Internal Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁸ Hybrid Technology Hub Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁹ Section of Transplant Surgery, Department of Transplantation Medicine, Division of Surgery and Specialized Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
¹⁰ Department of Upper Abdominal Diseases, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Background & aims: Liver transplantation (LT) to prevent cholangiocarcinoma (CCA) in individuals with primary sclerosing cholangitis (PSC) and bile duct dysplasia was introduced in Norway and Sweden in the early 2000s. We aimed to evaluate this practice to potentially improve future selection of candidates for LT.

Methods: We conducted a retrospective study of 512 adults with PSC who underwent first-time LT between 2000-2021 at Oslo and Karolinska University Hospitals. Pre-LT findings in bile duct brush cytology and/or biopsy of low-grade dysplasia (LGD) and high-grade dysplasia (HGD) were compared with histological findings in the explanted livers and survival rates were assessed.

Results: Bile duct dysplasia, low-grade (LGD) or high-grade (HGD), was the primary LT indication in 17% (88/512). Among individuals transplanted for LGD, only 10% (3/29) had HGD or CCA in the explant, compared to 48% (28/59) in the HGD group. No neoplasia was found in 42% (12/29) of LGD and 24% (14/59) of HGD cases, meaning nearly one-third of patients transplanted for suspected bile duct dysplasia had no histological evidence of neoplasia in the explant. Five-year post-transplant survival according to the explant histology was 95% for no neoplasia, 89% for LGD, 85% for HGD, decreasing to 33% in those with CCA in the explant.

Conclusions: While favorable survival in confirmed dysplasia supports the role of preemptive LT, the absence of neoplasia in a substantial proportion of explants, particularly in suspected LGD, calls for a cautious, individualized approach. LT appears more clearly justified in accurately diagnosed HGD, given its strong association with early malignancy and the poor prognosis of advanced CCA.

Impact and implications: Individuals with primary sclerosing cholangitis (PSC) are at increased risk of developing bile duct cancer. In precancerous stages (bile duct dysplasia), liver transplantation (LT) may prevent progression to advanced, incurable cancer. In our evaluation of 512 patients with PSC who underwent LT, we found that the low diagnostic accuracy and unpredictable detection of mild dysplasia support a cautious, individualized approach to LT in precancerous stages of PSC, while more advanced dysplasia remains a valid indication for LT.

Keywords: Bile duct dysplasia; Cholangiocarcinoma (CCA); Liver transplantation (LT); Primary sclerosing cholangitis (PSC).