What are the indications and dosing guidelines for Ursodeoxycholic acid (UDCA) in treating liver diseases?

Indications for Ursodeoxycholic Acid (UDCA)

UDCA at 13-15 mg/kg/day is the established first-line treatment for primary biliary cholangitis (PBC), while its use in primary sclerosing cholangitis (PSC) is NOT routinely recommended due to lack of proven clinical benefit and potential harm at higher doses. 1, 2

Established Indications

Primary Biliary Cholangitis (PBC)

• UDCA at 13-15 mg/kg/day is the treatment of choice for PBC, administered as a single bedtime dose 1, 2, 3
• This dosage significantly decreases serum bilirubin, alkaline phosphatase, cholesterol, and immunoglobulin M levels compared to placebo 1, 3
• Long-term treatment delays histological progression when started at early disease stages 1, 3
• Treatment reduces the likelihood of liver transplantation or death in patients with moderate to severe PBC 1, 2, 3
• UDCA should be continued during pregnancy and breastfeeding in women with PBC 4, 1

Intrahepatic Cholestasis of Pregnancy (ICP)

• UDCA at 10-15 mg/kg/day divided into 2-3 doses is recommended for ICP 1, 2, 3
• Pruritus typically decreases within 1-2 weeks, with biochemical improvement within 3-4 weeks 2
• If pruritus persists, the dose can be titrated to a maximum of 21 mg/kg/day 2
• In ICP with serum bile acid concentrations >40 μmol/L, UDCA may reduce the risk of spontaneous preterm birth and potentially protect against stillbirth 3

Conditional/Limited Evidence Indications

Primary Sclerosing Cholangitis (PSC)

Critical Warning: UDCA is NOT routinely recommended for PSC 4, 1, 2

• Low-to-medium dose UDCA (10-15 mg/kg/day) improves liver biochemistry but does NOT improve clinical outcomes including death, transplantation, or disease progression 4, 2
• Moderate-dose UDCA (15-20 mg/kg/day) may be considered in select cases as it can improve serum liver tests and surrogate markers of prognosis, though evidence does not support a firm recommendation 4, 1, 2
• High-dose UDCA (28-30 mg/kg/day) MUST BE AVOIDED in PSC due to increased serious adverse events, higher rates of death, liver transplantation, and development of varices 4, 2
• UDCA should be continued during pregnancy in women with PSC who are already on treatment 4

ABCB4 Deficiency

• Low-to-medium-dose UDCA (10-15 mg/kg/day) can be given in patients with ABCB4 deficiency, though available data does not allow a firmer recommendation 4
• UDCA provides litholytic and cholangioprotective properties for small duct sclerosing cholangitis and low phospholipid-associated cholelithiasis syndrome 4

Sclerosing Cholangitis in Critically Ill Patients (SC-CIP)

• Low-to-medium-dose UDCA (10-15 mg/kg/day) can be given in patients with SC-CIP, though available data does not allow a firmer recommendation 4
• UDCA exerts anticholestatic and anti-inflammatory effects while stimulating biliary bicarbonate secretion 4

Mechanism of Action

UDCA works through three major mechanisms 5:

• Protection of cholangiocytes against cytotoxicity of hydrophobic bile acids by changing bile acid composition from hydrophobic to more hydrophilic 3, 5
• Stimulation of hepatobiliary secretion through posttranscriptional mechanisms and ductular alkaline choleresis 3, 5
• Protection of hepatocytes against bile acid-induced apoptosis 5

Monitoring Requirements

• Regular monitoring of liver biochemistry is essential to assess treatment response 1, 2, 3
• Biochemical response should be evaluated after 1 year of therapy to identify patients at risk of progressive disease 2
• In PBC, AMA-positive individuals with normal liver tests should undergo annual reassessment of biochemical markers of cholestasis 3
• In ICP, serum bile acids should be checked at least weekly as they may continue to rise with advancing gestation 3

Common Pitfalls to Avoid

• Do not use high-dose UDCA (28-30 mg/kg/day) in PSC patients - this is associated with worse outcomes 4, 2
• Do not routinely prescribe UDCA for newly diagnosed PSC - the evidence does not support benefit and may cause harm 4, 1, 2
• UDCA has not demonstrated significant effects on symptoms like fatigue or pruritus in PBC, so do not use symptom relief as a marker of efficacy 1
• Obeticholic acid should be discontinued as soon as pregnancy is confirmed and should not be restarted during breastfeeding 4