What is the use of Ursodiol (Ursodeoxycholic acid)?

From the Guidelines

Ursodiol should not be used for the routine treatment of newly diagnosed primary sclerosing cholangitis (PSC) due to lack of evidence showing improvement in outcomes and potential harm in high doses. The use of ursodiol, also known as ursodeoxycholic acid (UDCA), has been extensively studied in the context of PSC, a chronic liver disease characterized by inflammation and scarring of the bile ducts. Despite its efficacy in improving liver biochemistry, numerous studies, including randomized controlled trials and meta-analyses, have failed to demonstrate a significant benefit of UDCA in improving clinical outcomes, such as reducing mortality, liver transplantation, or disease progression in PSC patients 1.

Key Points

• UDCA improves liver biochemistry but has no significant effect on clinical outcomes in PSC patients.
• High-dose UDCA (28-30 mg/kg/day) may be harmful, with increased rates of serious adverse events and primary endpoints such as death, liver transplantation, and development of varices.
• The British Society of Gastroenterology and UK-PSC guidelines recommend against the routine use of UDCA for newly diagnosed PSC, with a strong recommendation and good quality of evidence 1.
• For patients already established on UDCA therapy, there may be evidence of harm in those taking high-dose UDCA, although the quality of evidence is low.

Clinical Considerations

• Patients with PSC should be closely monitored for disease progression and complications, regardless of UDCA treatment.
• Alternative treatment options, such as endoscopic and surgical interventions, should be considered for patients with advanced disease or complications.
• Regular follow-up with healthcare providers is essential to assess treatment effectiveness and adjust management plans as needed.

Evidence Summary

• A large, 5-year study of 219 patients with PSC found no significant difference in outcomes between moderate-dose UDCA (17-23 mg/kg) and placebo, although there was a trend towards reduced mortality or transplantation in the UDCA group 1.
• A multicenter study of high-dose UDCA (28-30 mg/kg) in 150 patients with PSC was terminated early due to higher rates of serious adverse events and primary endpoints in the UDCA-treated group 1.
• Meta-analyses of published data have consistently shown no benefit of UDCA in patients with PSC, with some suggesting potential harm in high doses 1.

From the FDA Drug Label

Ursodiol capsules are indicated for patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in whom elective cholecystectomy would be undertaken except for the presence of increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or for those patients who refuse surgery. Ursodiol capsules are indicated for the prevention of gallstone formation in obese patients experiencing rapid weight loss.

The main indications for ursodiol are:

• Treatment of patients with radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter who are at increased surgical risk
• Prevention of gallstone formation in obese patients experiencing rapid weight loss The safety of use of ursodiol capsules beyond 24 months is not established 2

From the Research

Ursodiol Studies

• The studies on ursodiol, also known as ursodeoxycholic acid (UDCA), have shown its effectiveness in treating primary biliary cirrhosis (PBC) 3, 4, 5, 6, 7.
• A study published in 1999 found that the optimum dose of UDCA is 900 mg/day, which is equivalent to 13.5 mg/kg/day 3.
• Another study published in 1994 found that long-term treatment with ursodiol slows the progression of primary biliary cirrhosis and reduces the need for liver transplantation 4.
• A multicenter, controlled trial published in 1991 found that ursodiol is a safe and effective treatment for primary biliary cirrhosis, improving serum levels of bilirubin, alkaline phosphatase, and other liver function tests 5.
• A study published in 1993 found that long-term treatment with ursodiol improves clinical and biochemical features, and biliary bile acid metabolism in patients with primary biliary cirrhosis 6.
• Another study published in 1993 found that ursodeoxycholic acid therapy improves liver function tests, and changes in bile acid patterns are correlated with liver function 7.

Dosage and Efficacy

• The dosage of ursodiol used in the studies ranged from 10-15 mg/kg/day 4, 5.
• The studies found that ursodiol is effective in improving liver function tests, reducing symptoms, and slowing the progression of primary biliary cirrhosis 3, 4, 5, 6, 7.
• The optimum dose of 900 mg/day was found to be the most efficacious in a study published in 1999 3.

Mechanism of Action

• The mechanism of action of ursodiol is not fully understood, but it is thought to involve the replacement of toxic bile acids with ursodeoxycholic acid, which is a non-toxic bile acid 7.
• The studies found that ursodiol improves biliary bile acid metabolism, and changes in bile acid patterns are correlated with liver function 6, 7.