What are the emerging treatment options for Primary Sclerosing Cholangitis (PSC) beyond Ursodeoxycholic acid (UDCA)?

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Last updated: October 11, 2025 • View editorial policy

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

Currently, there are no established medical therapies for PSC beyond UDCA, which itself has limited efficacy and is not universally recommended due to lack of proven survival benefit and potential harm at high doses. 1

Current Status of UDCA in PSC

  • 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 1
  • The 2019 British Society of Gastroenterology guidelines strongly recommend against routine use of UDCA for newly diagnosed PSC 1
  • Withdrawal of UDCA in patients already established on therapy results in deterioration of liver biochemistry and may worsen pruritus 2

Emerging Therapeutic Options

Bile Acid-Based Therapies

  • 24-norursodeoxycholic acid (norUDCA, renamed as nor-ucholic acid or NCA) is being investigated as a potential therapy 1
  • Farnesoid X receptor (FXR) agonists, including obeticholic acid, represent another bile acid-based approach under investigation 1

Immunomodulatory Approaches

  • Corticosteroids and immunosuppressive agents are recommended only for PSC patients with overlap syndromes (particularly PSC/AIH overlap) 1
  • Various immunosuppressants have been studied in small trials, including:
    • Prednisolone and budesonide
    • Azathioprine
    • Cyclosporin
    • Methotrexate
    • Mycophenolate
    • Tacrolimus 1
  • TNF antagonists (pentoxifyllin, etanercept, anti-TNF monoclonal antibodies) have been investigated but without proven efficacy in classic PSC 1

Antifibrotic Agents

  • Antifibrotic agents including colchicine, penicillamine, and pirfenidone have been studied but without demonstrated efficacy 1

Antimicrobial Therapy

  • Metronidazole in combination with UDCA has shown some promise in improving liver biochemistry and Mayo Risk Score, though effects on disease progression were not statistically significant 3

Management of Complications

Dominant Bile Duct Strictures

  • Endoscopic treatment is recommended for dominant bile duct strictures 4
  • ERCP with brush cytology and/or biopsy sampling should be performed when clinically indicated 1

Cholangiocarcinoma Management

  • Early diagnosis of cholangiocarcinoma remains challenging with no established screening modality 1
  • Neoadjuvant radiochemotherapy with subsequent liver transplantation may be considered in selected patients with cholangiocarcinoma 4

Bone Health Management

  • Assessment of fracture risk is recommended for all PSC patients 1
  • Vitamin D supplementation in cases of deficiency and adequate calcium intake are advisable 1

Clinical Trials and Future Directions

  • The lack of effective medical therapy highlights the need for continued clinical trials
  • Liver transplantation remains the only definitive treatment for advanced PSC 1
  • Combined approaches targeting multiple pathways (inflammation, fibrosis, bile acid metabolism) may be necessary given the complex pathophysiology of PSC

Pitfalls and Caveats

  • Avoid high-dose UDCA (>28 mg/kg/day) due to potential harm 1
  • Recognize PSC/AIH overlap syndromes which may benefit from immunosuppressive therapy unlike classic PSC 1
  • Monitor for development of dominant strictures and cholangiocarcinoma, which significantly impact prognosis 1
  • Be aware that withdrawal of UDCA in patients already on therapy can lead to biochemical deterioration and worsening symptoms 2

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Research

Management of primary sclerosing cholangitis.

World journal of hepatology, 2011

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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