What is primary biliary cholangitis (PBC)?

From the Guidelines

Primary biliary cholangitis (PBC) patients should be treated with ursodeoxycholic acid (UDCA) at a dose of 10-15 mg/kg/day to prevent recurrence after liver transplantation, as recommended by the most recent guidelines 1. The treatment of PBC involves the use of UDCA, which has been shown to improve liver function, reduce symptoms, and slow disease progression.

• The dose of UDCA recommended is 10-15 mg/kg/day, given in two divided doses.
• UDCA works by protecting bile duct cells from toxic effects of bile acids, stimulating biliary secretion, and having immunomodulatory effects.
• For patients who have an inadequate response to UDCA after 12 months of treatment, obeticholic acid (OCA) at 5-10 mg daily can be added as second-line therapy, but its use during pregnancy or lactation is not recommended due to lack of safety data 1.
• Patients should be monitored regularly with liver function tests every 3-6 months to assess treatment response.
• Symptom management is also important, with cholestyramine (4 g up to four times daily) for pruritus and fat-soluble vitamin supplementation (vitamins A, D, E, and K) for those with advanced disease.
• Patients should be screened for complications like osteoporosis and monitored for progression to cirrhosis.
• The choice of immunosuppressive regimen after liver transplantation should consider medication adherence, and a double immunosuppressive regimen combining tacrolimus with an anti-metabolite may allow for safe corticosteroid withdrawal 1.
• The UK-PBC score and GLOBE score can be used to predict the risk of major outcomes, such as liver-related death, liver transplantation, or bilirubin >100 µmol/L, and to refine risk stratification in patients with PBC 1.

From the FDA Drug Label

OCALIVA is a prescription medicine used to treat primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA) in adults who have not responded well enough to UDCA, or alone in adults who cannot tolerate UDCA. It is not known if taking OCALIVA will improve your chance of survival or improve your symptoms of PBC. WARNING: HEPATIC DECOMPENSATION AND FAILURE IN PRIMARY BILIARY CHOLANGITIS PATIENTS WITH CIRRHOSIS Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in primary biliary cholangitis (PBC) patients with either compensated or decompensated cirrhosis

Primary Biliary Cholangitis (PBC) Treatment: Obeticholic acid (OCALIVA) is used to treat PBC in adults who have not responded well enough to UDCA, or alone in adults who cannot tolerate UDCA 2.

• Key Points:
  • OCALIVA is used in combination with UDCA or alone in adults with PBC.
  • The medication may cause serious side effects, including hepatic decompensation and failure, especially in patients with cirrhosis 2.
  • Patients should be monitored for signs of disease progression or worsening liver function while on OCALIVA treatment.
• Contraindications: OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension 2.

From the Research

Primary Biliary Cholangitis Treatment

• Ursodeoxycholic acid is the preferred first-line therapy for primary biliary cholangitis, as stated in the study 3.
• Alternative therapies, such as obeticholic acid, are recommended for patients who cannot tolerate ursodeoxycholic acid or who have an inadequate response to ursodeoxycholic acid monotherapy 3.
• Obeticholic acid has been shown to improve cholestasis, liver fibrosis, and liver function in patients with primary biliary cholangitis with inadequate response to ursodeoxycholic acid 4.

Patient Response to Treatment

• A study found that 95% of patients were taking ursodeoxycholic acid for treatment of their primary biliary cholangitis, with 67% of patients having disease that was well-controlled on ursodeoxycholic acid monotherapy 3.
• Only 3% of patients were not on any medication for management of their primary biliary cholangitis 3.
• Obeticholic acid treatment led to a statistically significant decrease in aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase, while the decrease in alkaline phosphatase was not statistically significant 4.

Future Therapies

• New and creative approaches to treating patients with primary biliary cholangitis are important to identify, as current treatments may not be sufficient to prevent progression to hepatic decompensation and/or need for liver transplant 5.
• Potential therapeutic targets in primary biliary cholangitis include modifying bile, inflammation, cell survival, or fibrosis, and examples of specific agents currently in development for the treatment of primary biliary cholangitis are discussed in the literature 5.
• The nuclear hormone receptors, farnesoid X receptor and peroxisome proliferator-activated receptor, regulate many of these pathways and are being pursued as potential therapeutic targets in primary biliary cholangitis 5.

Second-Line Therapies

• Obeticholic acid is the only registered agent for second-line treatment in ursodeoxycholic acid non-responders 6.
• Bezafibrate is another option in patients with inadequate response to ursodeoxycholic acid, as it has been proven to improve surrogate endpoints, pruritus, and even clinical outcome compared with ursodeoxycholic acid monotherapy 7.
• Budesonide may be considered in patients with marked portal inflammation 7.
• Triple therapy with ursodeoxycholic acid, obeticholic acid, and bezafibrate may be considered in patients showing inadequate response to dual therapy 7.