Emerging Treatment Options for Primary Sclerosing Cholangitis (PSC) Beyond UDCA

Current Status of UDCA in PSC

The British Society of Gastroenterology strongly recommends against routine use of UDCA for newly diagnosed PSC, due to limited efficacy and potential harm at high doses 2
UDCA at doses of 15-20 mg/kg/day may improve serum liver tests and surrogate markers of prognosis, but lacks evidence for improving hard clinical endpoints like survival 1
High-dose UDCA (28-30 mg/kg/day) has been associated with increased adverse events and potentially worse outcomes 2, 3

24-norursodeoxycholic acid (norUDCA) is being investigated as a potential therapy for PSC, with ongoing clinical trials 4
Farnesoid X receptor (FXR) agonists, including obeticholic acid, represent another bile acid-based approach under investigation for PSC treatment 4

The American Association for the Study of Liver Diseases recommends corticosteroids and immunosuppressive agents only for PSC patients with overlap syndromes, such as PSC/AIH overlap 5, 6
Various immunosuppressants, including prednisolone, budesonide, azathioprine, cyclosporin, methotrexate, mycophenolate, and tacrolimus, have been studied in small trials for PSC treatment 5, 6, 7

Antifibrotic agents, including colchicine, penicillamine, and pirfenidone, have been studied but without demonstrated efficacy in PSC treatment 6

ERCP with brush cytology and/or biopsy sampling should be performed when clinically indicated for dominant bile duct strictures in PSC patients 8, 9

Early diagnosis of cholangiocarcinoma remains challenging, with no established screening modality, and highlights the need for regular monitoring in PSC patients 8, 9

Assessment of fracture risk is recommended for all PSC patients, with vitamin D supplementation and adequate calcium intake advisable in cases of deficiency 1

Liver transplantation remains the only definitive treatment for advanced PSC, with ongoing clinical trials investigating new therapeutic approaches 5, 6
Combined approaches targeting multiple pathways, including inflammation, fibrosis, and bile acid metabolism, may be necessary for effective PSC treatment 6