What are the indications for long-term ursodiol (ursodeoxycholic acid) therapy?

From the Guidelines

Ursodiol is primarily indicated for long-term use in primary biliary cholangitis (PBC) to prevent recurrence, with a standard dosage of 13-15 mg/kg/day, as recommended by the most recent guidelines 1.

Indications for Long-Term Ursodiol Therapy

• Primary biliary cholangitis (PBC): Ursodiol is used to prevent recurrence of PBC after liver transplantation, with a strong recommendation for lifelong use 1.
• Primary sclerosing cholangitis (PSC): Although the role of ursodiol in PSC is unclear, high-dose ursodiol may be harmful in late-stage disease, and its use should be approached with caution 1.
• Intrahepatic cholestasis of pregnancy: Ursodiol may be used to manage this condition, but the evidence is limited.
• Prevention of gallstones: Ursodiol may be used to prevent gallstones in patients undergoing rapid weight loss.

Mechanism of Action and Side Effects

Ursodiol works by decreasing cholesterol secretion into bile, reducing intestinal absorption of cholesterol, and protecting liver cells from damage caused by toxic bile acids. Common side effects include diarrhea, nausea, and abdominal discomfort. Patients should be monitored with liver function tests periodically during treatment.

Quality of Life and Morbidity Considerations

Ursodiol is generally well-tolerated even with prolonged use, making it suitable for chronic conditions requiring long-term therapy. However, patients should be closely monitored for potential side effects and liver function test abnormalities. The benefits of ursodiol therapy in preventing recurrence of PBC and other indications should be weighed against the potential risks and side effects, with a focus on improving quality of life and reducing morbidity.

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 indications for long-term ursodiol are:

• Dissolution of radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter in patients who are unable to or refuse to undergo surgery.
• Prevention of gallstone formation in obese patients experiencing rapid weight loss. Note that safety of use of ursodiol beyond 24 months is not established 2

From the Research

Indications for Long-Term Ursodiol

The indications for long-term ursodiol therapy are primarily based on its efficacy in treating certain liver diseases. Key points include:

• Primary biliary cirrhosis (PBC) is a major indication for long-term ursodiol therapy, as evidenced by studies showing its ability to slow disease progression and reduce the need for liver transplantation 3, 4.
• Ursodiol has been shown to improve biochemical test results for liver function in patients with PBC and has been associated with improved survival without the need for liver transplantation after 4 years of treatment 5.
• The dosage of ursodiol recommended for the treatment of PBC is 13 to 15 mg/kg/d 6.
• Primary sclerosing cholangitis (PSC) does not appear to benefit from ursodiol therapy in terms of clinical outcomes, despite improvements in serum alkaline phosphatase, aspartate aminotransferase, bilirubin, and albumin levels 7.
• Liver transplantation remains the treatment of choice for patients with end-stage liver disease due to PBC or PSC 6.

Disease-Specific Considerations

Considerations for specific diseases include:

• Primary biliary cirrhosis:
  • Ursodiol slows disease progression and reduces the need for liver transplantation.
  • High bilirubin levels and signs of cirrhosis at entry into the trial are predictive of disease progression.
• Primary sclerosing cholangitis:
  • Ursodiol does not provide significant clinical benefits.
  • No medical therapy aimed at disrupting disease progression is currently available.