What is ursodeoxycholic acid used for in adults with a history of liver or gallbladder disease?

Ursodeoxycholic Acid: Clinical Indications

Ursodeoxycholic acid (UDCA) is primarily used for treating cholestatic liver diseases, particularly primary biliary cirrhosis, and for dissolving small radiolucent gallstones in patients who cannot undergo surgery. 1

Primary Indications

Cholestatic Liver Diseases

Primary Biliary Cirrhosis (PBC) represents the strongest indication for UDCA therapy. 1

• UDCA at 13-15 mg/kg/day is the first-line treatment recommended by the American Association for the Study of Liver Diseases for primary biliary cirrhosis. 1
• This dosing significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels. 1
• Long-term treatment delays histological progression when started early in the disease course. 1
• UDCA reduces the risk of liver transplantation or death in patients with moderate to severe PBC. 1
• The medication prolongs transplant-free survival in PBC patients. 2

Primary Sclerosing Cholangitis (PSC) has more nuanced recommendations:

• UDCA at 13-20 mg/kg/day improves serum liver chemistries and surrogate markers of prognosis. 2
• However, high-dose UDCA (>20 mg/kg/day) is associated with worse outcomes in PSC and must be avoided. 1, 3
• The British Society of Gastroenterology recommends against routine use of UDCA for newly diagnosed PSC due to limited efficacy. 1

Gallstone Disease

UDCA is FDA-approved for dissolving radiolucent, noncalcified gallbladder stones < 20 mm in greatest diameter. 4

• This indication applies specifically to patients who would otherwise undergo elective cholecystectomy but have increased surgical risk due to systemic disease, advanced age, idiosyncratic reaction to general anesthesia, or patient refusal of surgery. 4
• UDCA is also indicated for preventing gallstone formation in obese patients experiencing rapid weight loss. 4
• Safety beyond 24 months of use is not established. 4

Other Cholestatic Conditions

Intrahepatic Cholestasis of Pregnancy:

• UDCA at 10-15 mg/kg/day has beneficial effects. 1
• The medication is considered safe during pregnancy and breastfeeding. 1

Additional cholestatic conditions where UDCA shows benefit include: 2, 5

• Liver disease associated with cystic fibrosis
• Progressive familial intrahepatic cholestasis
• Chronic graft-versus-host disease
• Total parenteral nutrition-associated cholestasis
• Various pediatric cholestatic liver diseases

Mechanisms of Action

UDCA works through multiple pathways that explain its therapeutic effects: 6, 2

• Replaces toxic hydrophobic bile acids with hydrophilic ones, modifying the bile acid pool composition
• Protects hepatocytes and cholangiocytes from apoptosis by modulating mitochondrial membrane perturbation and reducing reactive oxygen species 6
• Stimulates impaired bile secretion through calcium-dependent and protein kinase C-alpha-dependent mechanisms 2
• Exerts immunomodulatory effects on monocyte cytokine production and MHC class II gene expression 6

Important Clinical Considerations

Monitoring Requirements:

• Regular monitoring of liver biochemistry (alkaline phosphatase and GGT) is essential to assess treatment response. 1
• Alkaline phosphatase and GGT are the earliest cholestasis markers and should be checked regularly. 1

Adverse Effects:

• UDCA is generally well tolerated. 1
• Nausea and mild dizziness may occur in up to 25% of patients. 1

Critical Pitfall:

• Never use high-dose UDCA (>20 mg/kg/day) in primary sclerosing cholangitis, as this is associated with significantly worse outcomes. 1, 3

Symptom Management:

• UDCA does not significantly improve fatigue or pruritus in PBC, so additional treatments (such as rifaximin for pruritus) may be needed for symptom management. 1