Recent advances in the treatment of primary sclerosing cholangitis

ABSTRACT

Introduction: PSC is a rare liver disease that leads frequently to cirrhosis and need for liver transplantation. No medical treatment is of proven value. Liver transplantation is the only curative therapy available. There is a big medical need to find medical therapy that can alter the natural history of the disease.

Areas covered: The authors highlight advances in PSC, based on recent literature retrieved from PubMed until September 2020 regarding both medical and endoscopic biliary therapy.

Future possibilities for treatment of PSC are discussed.

Expert opinion: Biliary endoscopy is the cornerstone in the treatment of dominant strictures. Single-user peroral cholangioscopy is an emerging modality. Balloon dilatation therapy is the treatment of choice of dominant strictures. The most promising medical therapies showing efficacy in phase II trials are nor-Ursodeoxycholic acid, obethicolic acid, the non-steroidal FXR agonist Cilofexor and Aldafermin, a synthetic analogue of FGF-19. Antibiotics, particularly vancomycin have shown potential benefits, particularly in children but phase III studies are lacking. In observational studies of effects of biological therapy in patients with IBD/PSC adalimumab was associated with reduction in ALP. Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.

KEYWORDS:

• Primary sclerosing cholangitis
• inflammatory bowel disease
• biliary endoscopy
• cholangiocarcinoma
• Igg4
• nor-Ursodeoxycholic acid
• obethicolic acid
• liver transplantation

Article highlights

• PSC can be divided into subtypes requiring different type of management such as small duct PSC requiring a liver biopsy for diagnosis, overlap with autoimmune hepatitis often requiring corticosteroids and those with elevated IgG4 levels who can also respond to corticosteroids.

• Balloon dilatation therapy is the first-line endoscopic therapy for dominant strictures in patients with PSC. Further research is warranted to investigate whether patients with dominant strictures should be treated with scheduled rather than on-demand ERCP with balloon dilatation.

• nor-Ursodeoxycholic acid (nor-UDCA) which is a more potent inducer of bile flow than UDCA has been tested in a phase II study in PSC patients and was found to have a good safety profile and treatment with nor-UDCA was associated with reduced ALP levels in a dose dependent manner, up to 26% in the group given the highest dose. Phase III trial is ongoing.

• Obethicolic acid (OCA), the selective farnesoid X receptor agonist marketed for PBC, has also been tried in a phase II trial in PSC. Treatment with OCA was associated with a significant reduction in ALP in patient receiving 5-10 mg OCA vs. placebo but not significantly in those receiving 1.5-3.0 mg.

• Antibiotics, in particular vancomycin, have shown positive effects on ALP in PSC patients, both children and adults. As with other medical therapy phase III clinical trials are still lacking.

• Results of liver transplantation are favorable but recurrence can be of clinical relevance particularly in patients transplanted before the age of 40.

Conflict of interest

The authors report no conflicts of interests.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.