From the Guidelines
Ursodeoxycholic acid (UDCA) is the treatment of choice for patients with Primary Biliary Cholangitis (PBC), with a recommended dose of 13-15 mg/kg/d, as it has been shown to improve liver function, delay disease progression, and potentially reduce the likelihood of liver transplantation or death 1.
Key Points
- UDCA has been demonstrated to exert anticholestatic effects in various cholestatic disorders, including PBC, by protecting injured cholangiocytes, stimulating impaired hepatocellular secretion, and inhibiting bile acid-induced hepatocyte and cholangiocyte apoptosis 1.
- The treatment with UDCA has been shown to decrease serum bilirubin, AP, cGT, cholesterol, and immunoglobulin M levels, and to ameliorate histological features in patients with PBC, although it has no significant effects on fatigue or pruritus 1.
- A beneficial effect of UDCA on survival has been demonstrated in a combined analysis of the raw data from the French, Canadian, and Mayo cohorts, with a significant reduction in the likelihood of liver transplantation or death in patients with moderate and severe disease 1.
Recommendations
- Patients with PBC, including those with asymptomatic disease, should be treated with UDCA (13-15 mg/kg/d) on a long-term basis, with favorable long-term effects observed in patients with early disease and good biochemical response 1.
- A good biochemical response after one year of UDCA treatment is currently defined by a serum bilirubin ≤ 1 mg/dL (17 µmol/L), AP ≤ 3 ULN, and AST ≤ 2 ULN (“Paris criteria”) or by a decrease of 40% or normalization of serum AP (“Barcelona criteria”) 1.
From the Research
Ursodeoxycholic Acid in Primary Biliary Cholangitis
- Ursodeoxycholic acid (UDCA) is the only approved first-line medicine for primary biliary cholangitis (PBC) 2.
- The optimum dose of UDCA is 900 mg/day (equivalent to 13.5 mg/kg/day) 3.
- However, some studies suggest that a higher dose of 18-22 mg/kg/day may be beneficial for patients who do not respond completely to the standard dose of UDCA 4.
- UDCA has been shown to improve liver function tests and prolong survival in PBC patients 3, 5.
- Despite its benefits, 30-40% of patients do not respond to UDCA, and these patients are at high risk for serious complications 5, 6.
Response to UDCA Treatment
- The response to UDCA treatment can be affected by various factors, including gender, age, ethnicity, serum indicators, auto-antibodies, and autoimmune comorbidities 2.
- Patients with poor UDCA response usually have more adverse outcomes and worse survival 2.
- The management of patients with poor UDCA response is a major consideration, and second-line therapies such as obeticholic acid (OCA) may be necessary 5, 6.
Alternative Therapies
- OCA is a first-in-class FXR agonist that has shown promising results in PBC patients with inadequate response to UDCA 5, 6.
- Other alternative therapies, such as 6-ECDCA, are also being examined in PBC patients 6.
- The use of OCA in addition to UDCA has been shown to lead to significant reduction of serum alkaline phosphatase (ALP) in PBC patients 6.