From the Guidelines
Berberine and Ursodeoxycholic acid (UDCA) are not currently recommended as standard treatments for Primary Sclerosing Cholangitis (PSC), and patients should focus on established management approaches. The use of UDCA in PSC is widely accepted by patients and treating physicians across many countries, although it is licensed for treatment of PSC in some European countries such as France or Switzerland 1. According to the EASL clinical practice guidelines on sclerosing cholangitis, UDCA has broad anti-cholestatic, cytoprotective, anti-inflammatory, and antifibrotic actions, which are used to treat a wide range of cholestatic liver diseases, including PSC 1.
However, the British Society of Gastroenterology and UK-PSC guidelines for the diagnosis and management of primary sclerosing cholangitis recommend that UDCA is not used for the prevention of colorectal cancer or cholangiocarcinoma, with a strong recommendation and high-quality evidence 1. The guidelines also recommend that corticosteroids and immunosuppressants are not indicated for the treatment of classic PSC, with a strong recommendation and high-quality evidence 1.
In terms of management approaches, the guidelines recommend that patients with PSC should have a risk assessment for osteoporosis, and that poor nutrition and fat-soluble vitamin deficiency should be treated empirically 1. The guidelines also suggest that cholestyramine (or similar) is first-line medical treatment for pruritus, and that rifampicin and naltrexone are second-line treatments 1.
Berberine, a plant compound with anti-inflammatory properties, has shown some promise in other liver conditions but lacks robust clinical evidence for PSC. Therefore, patients with PSC should focus on established management approaches, including monitoring for complications, addressing symptoms, and considering liver transplantation when appropriate, rather than pursuing experimental treatments with berberine or UDCA. Any experimental treatment should only be pursued under medical supervision as PSC is a complex progressive liver disease affecting the bile ducts that requires comprehensive care from hepatology specialists.
Key management approaches for PSC include:
- Monitoring for complications such as colorectal cancer and cholangiocarcinoma
- Addressing symptoms such as pruritus and fatigue
- Considering liver transplantation when appropriate
- Risk assessment for osteoporosis and treatment of poor nutrition and fat-soluble vitamin deficiency
- Referral to a centre participating in clinical trials for patients meeting inclusion criteria 1.
From the Research
Role of Ursodeoxycholic Acid (UDCA) in Primary Sclerosing Cholangitis (PSC)
- UDCA has been proposed as a potential treatment for PSC, but its effectiveness is still debated 2, 3.
- Meta-analyses have shown that UDCA, whether at standard or high doses, does not significantly influence the progression of PSC, including mortality, liver transplantation, pruritus, fatigue, cholangiocarcinoma, and histological progression 2, 3.
- Some studies suggest that UDCA may improve liver function tests (LFTs), but it does not decrease the risk of mortality or the need for liver transplant 3.
- High-dose UDCA has been associated with increased mortality in one large randomized trial 3.
Role of Berberine in Primary Sclerosing Cholangitis (PSC)
- Berberine ursodeoxycholate (HTD1801) is a novel compound that combines berberine and ursodeoxycholic acid, with potential pleiotropic mechanisms of action 4.
- A randomized, dose-finding, proof-of-concept study found that HTD1801 significantly decreased alkaline phosphatase (ALP) levels in patients with PSC, suggesting a potential therapeutic effect 4.
- The study also found that HTD1801 was generally well-tolerated, with no serious adverse events attributed to the treatment 4.
Combination Therapy and Future Directions
- Successful PSC therapy may involve a personalized combination of different drugs, including UDCA, berberine, and other novel pharmacological agents, as well as endoscopic treatment 5.
- Further research is needed to establish the effectiveness of UDCA and other treatments in improving long-term prognosis for patients with PSC 6.
- Novel approaches, such as modulation of bile composition, immunomodulation, targeting the gut microbiome, and targeting fibrosis, are being explored as potential therapeutic strategies for PSC 5.