What is Ursodeoxycholic acid (UDCA) used for?

Therapeutic Applications of Ursodeoxycholic Acid (UDCA)

UDCA is primarily indicated for primary biliary cirrhosis (PBC) at doses of 13-15 mg/kg/day, where it significantly improves liver biochemistry, delays disease progression, and reduces the likelihood of liver transplantation or death. 1, 2

Primary Indications

• UDCA is FDA-approved for the dissolution of radiolucent, noncalcified gallstones less than 20mm in diameter in patients with increased surgical risk or who refuse surgery 3
• UDCA is also FDA-approved for the prevention of gallstone formation in obese patients experiencing rapid weight loss 3
• UDCA at 13-15 mg/kg/day is the established first-line treatment for primary biliary cirrhosis (PBC) based on multiple controlled trials 1, 2
• The optimal dose for PBC has been determined to be approximately 13.5 mg/kg/day (or 900 mg/day for average-sized adults) 4

Mechanism of Action

• UDCA exerts anticholestatic effects through multiple mechanisms including:
  • Protection of cholangiocytes against toxic effects of hydrophobic bile acids 5, 6
  • Stimulation of impaired hepatocellular secretion via posttranscriptional mechanisms 1
  • Stimulation of ductular alkaline choleresis 1
  • Inhibition of bile acid-induced hepatocyte and cholangiocyte apoptosis 5, 6
• UDCA changes bile acid composition from hydrophobic to more hydrophilic, reducing the amount of toxic bile acids 1

Clinical Effects in Primary Biliary Cirrhosis

• UDCA significantly decreases serum bilirubin, alkaline phosphatase, gamma-glutamyl transferase, cholesterol, and immunoglobulin M levels 1, 2
• Long-term UDCA treatment delays histological progression of PBC when started at an early stage 1
• UDCA treatment is associated with a significant reduction in the likelihood of liver transplantation or death in patients with moderate to severe PBC 1, 7
• UDCA has not demonstrated significant effects on symptoms like fatigue or pruritus in PBC 1, 2

Other Potential Applications

• UDCA may be considered for treatment of maternal pruritus in intrahepatic cholestasis of pregnancy (ICP) 1
• In ICP with serum bile acid concentrations >40 μmol/L, UDCA may reduce the risk of spontaneous preterm birth and potentially protect against stillbirth 1
• UDCA has been studied in primary sclerosing cholangitis (PSC), but current guidelines do not support its routine use due to limited efficacy and potential harm at high doses 8, 9

Dosing Considerations

• For PBC: 13-15 mg/kg/day is the recommended dose 1, 2
• For ICP: 10-15 mg/kg/day divided in 2-3 daily doses 2
• For PSC: While studied at doses of 15-20 mg/kg/day, high-dose UDCA (28-30 mg/kg/day) has been associated with increased adverse events 8, 9

Safety Considerations

• UDCA is generally well-tolerated with minimal side effects at recommended doses 2
• High-dose UDCA (28 mg/kg/day) has shown toxicity in PSC, including increased risk of death and liver transplantation 10
• Potential side effects include hepatitis, pruritus, cholangitis, and diarrhea 10
• The therapeutic window is relatively narrow, with recommended doses (13-15 mg/kg/day) being significantly lower than potentially toxic doses (28 mg/kg/day) 10

Monitoring

• Regular monitoring of liver biochemistry is essential to assess treatment response 2
• In PBC, AMA-positive individuals with normal liver tests should undergo annual reassessment of biochemical markers of cholestasis 1
• In ICP, serum bile acids should be checked at least weekly as they may continue to rise with advancing gestation 1