What is the dosage and treatment duration of Ursodeoxycholic acid (UDCA) for liver diseases and gallstones?

Ursodeoxycholic Acid (UDCA) Dosing and Duration

Primary Biliary Cholangitis (PBC)

For PBC, administer UDCA at 13-15 mg/kg/day as a single bedtime dose indefinitely, as this is the established first-line therapy that reduces risk of liver transplantation and death. 1, 2

• This dosing significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 1, 3
• Long-term treatment delays histological progression and may decrease liver fibrosis when started at early disease stages 1, 3
• Treatment is associated with significant reduction in likelihood of liver transplantation or death in patients with moderate to severe PBC 3, 2
• Continue therapy lifelong unless hepatic decompensation develops 3
• Evaluate biochemical response after 1 year to identify patients at risk of progressive disease 2

Monitoring Requirements

• Regular monitoring of liver biochemistry is essential to assess treatment response 3, 2
• AMA-positive individuals with normal liver tests should undergo annual reassessment of biochemical markers of cholestasis 1, 3

Gallstone Dissolution

For radiolucent cholesterol gallstones, use UDCA 8-10 mg/kg/day divided into 2-3 doses, with treatment duration of 6-24 months depending on stone response. 4

• Complete stone dissolution can be anticipated in approximately 30% of unselected patients with uncalcified gallstones <20 mm treated for up to 2 years 4
• Dissolution rates increase to 50% in patients with floating stones (high cholesterol content) and up to 81% for stones ≤5 mm in diameter 4
• Obtain ultrasound images at 6-month intervals for the first year to monitor gallstone response 4
• If partial stone dissolution is not seen by 12 months, the likelihood of success is greatly reduced and therapy should be discontinued 4
• Once stones appear dissolved, continue UDCA and confirm dissolution on repeat ultrasound within 1-3 months before stopping 4

Important Caveats

• Patients with calcified gallstones, stones >20 mm, or gallbladder nonvisualization developing during treatment rarely achieve dissolution and therapy should be discontinued 4
• Stone recurrence occurs in 30-50% of patients within 2-5 years after complete dissolution 4
• UDCA is ineffective for gallstones in cystic fibrosis patients, as cholesterol is not the main stone component 5

Gallstone Prevention During Rapid Weight Loss

For patients undergoing rapid weight loss, administer UDCA 600 mg/day (300 mg twice daily) throughout the weight loss period. 4

• This dosing is specifically for patients with BMI ≥38 undergoing very low calorie diets 4

Primary Sclerosing Cholangitis (PSC)

Do NOT routinely use UDCA for PSC, as it does not improve clinical outcomes and high doses may cause harm. 3, 2

• The American Association for the Study of Liver Diseases and British Society of Gastroenterology provide strong recommendations against routine UDCA use in PSC 3, 2
• Low-dose UDCA (10-15 mg/kg/day) improves liver biochemistry but does not improve death, transplantation, or disease progression 2
• Moderate-dose UDCA (15-20 mg/kg/day) may be considered in highly select cases as it can improve surrogate markers, though firm recommendations are not supported 3, 2
• High-dose UDCA (28-30 mg/kg/day) MUST BE AVOIDED due to increased serious adverse events, higher rates of death, liver transplantation, and development of varices 3, 2

Intrahepatic Cholestasis of Pregnancy (ICP)

For ICP, use UDCA 10-15 mg/kg/day divided into 2-3 doses starting from the second trimester until delivery. 1, 3, 2

• Decrease in pruritus typically occurs within 1-2 weeks, and biochemical improvement within 3-4 weeks 3, 2
• If pruritus is not relieved, titrate dose to maximum of 21 mg/kg/day 3, 2
• UDCA is safe during pregnancy and breastfeeding 3, 2
• Whether to continue UDCA postpartum should be decided based on individual family history, clinical presentation, presence of gallstones, laboratory values, and presence of liver disease 1

ABCB4 Deficiency (MDR3 Deficiency)

For patients with at least one ABCB4 missense variant and clinical phenotype, use UDCA 8-10 mg/kg/day lifelong. 1

• This is a strong recommendation based on evidence showing normalization of serum liver tests and stabilization of liver disease 1
• For LPAC syndrome specifically, lifelong UDCA at 8-10 mg/kg/day is recommended 1
• Patients carrying biallelic protein-truncating ABCB4 variants show partial or no response, but UDCA may still be offered 1
• Transplant-free survival was 91% with median follow-up of 14 years in treated patients 1

Renal Insufficiency Considerations

No dose adjustment is necessary for UDCA in renal insufficiency, as it is primarily metabolized in the liver and excreted through bile, not kidneys. 6

• The standard dose of 13-15 mg/kg/day remains constant even in patients with advanced chronic kidney disease 6
• It is not necessary to calculate creatinine clearance to adjust UDCA dose 6
• Monitoring of serum drug levels is not required in patients with renal insufficiency 6