What is the management of Primary Biliary Cholangitis (PBC)?

From the Guidelines

The management of Primary Biliary Cholangitis (PBC) centers on ursodeoxycholic acid (UDCA) as first-line therapy, typically prescribed at 13-15 mg/kg/day divided into 2-3 doses, as recommended by the most recent guidelines 1. UDCA should be initiated promptly after diagnosis to slow disease progression and improve liver biochemistry. For patients with inadequate response to UDCA (defined as alkaline phosphatase >1.67x upper limit of normal after 12 months), obeticholic acid (OCA) at 5-10 mg daily is recommended as second-line therapy. Symptom management is equally important:

• cholestyramine (4-16 g/day) or other bile acid sequestrants help control pruritus,
• while fatigue may require addressing contributing factors like anemia or hypothyroidism. Patients should be monitored for metabolic bone disease with DEXA scans and supplemented with calcium (1000-1500 mg/day) and vitamin D (1000-4000 IU/day) as needed. Fat-soluble vitamin supplementation (A, D, E, K) is necessary in advanced disease. Regular monitoring of liver biochemistry every 3-6 months is essential to assess treatment response. For those progressing to end-stage liver disease despite medical therapy, liver transplantation offers excellent outcomes, though PBC may recur in the transplanted liver in approximately 20% of patients over 10 years, and lifelong UDCA therapy is recommended after liver transplantation to prevent recurrence 1. Additionally, patients with PBC should be evaluated for the presence of symptoms, particularly fatigue and itch, and individualized risk stratification using biochemical response indices is recommended following 1 year of UDCA therapy 1. It is also important to note that the choice of immunosuppressive regimen should consider medication adherence, and a double immunosuppressive regimen combining tacrolimus with an anti-metabolite may allow for safe corticosteroid withdrawal 1. Overall, the management of PBC requires a comprehensive approach that includes UDCA therapy, symptom management, and regular monitoring, with the goal of improving liver biochemistry, reducing symptoms, and preventing disease progression.

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. The management of Primary Biliary Cholangitis (PBC) with obeticholic acid (OCALIVA) involves:

• Using OCALIVA in combination with ursodeoxycholic acid (UDCA) in adults who have not responded well enough to UDCA
• Using OCALIVA alone in adults who cannot tolerate UDCA Key considerations:
• Patients should be monitored for symptoms of disease progression or worsening liver function
• Patients should be advised to contact their healthcare provider if they experience severe or persistent non-specific signs and symptoms of impaired health
• Laboratory testing is necessary to assess liver function and lipid levels while on OCALIVA treatment 2

From the Research

Management of Primary Biliary Cholangitis (PBC)

• PBC is a rare progressive immune-mediated liver disease that, if not adequately treated, may culminate in end-stage disease and need for transplantation 3.
• The goal of therapy should be the normalization of ALP and bilirubin below 0.6 the upper limit of normal 4.
• First-line treatment for PBC is ursodeoxycholic acid (UDCA), which improves cholestatic surrogate markers and is associated with a favorable survival free of liver transplantation 5.

Treatment Options for Inadequate Response to UDCA

• Patients with inadequate response to UDCA may require second-line treatment, such as obeticholic acid (OCA) or fibrates, in addition to continued treatment with UDCA 4, 6, 7.
• OCA has proven to be effective in improving surrogate markers of prognosis in PBC, but may cause pruritus as an adverse event 4, 7.
• Fibrates, such as bezafibrate, have shown benefit in improving surrogate endpoints, pruritus, and clinical outcome compared with UDCA monotherapy 4, 7.
• Budesonide may be considered in patients with marked portal inflammation 4.
• Triple therapy with UDCA, OCA, and bezafibrate may be considered in patients showing inadequate response to dual therapy 4.

Risk Stratification and Monitoring

• Patients with PBC need to be evaluated at baseline and on-treatment for the risk of progressive disease and eventually treated with second-line therapies in addition to UDCA 4, 5, 6.
• Risk stratification tools are well established, but some issues, such as bile acid dosage in routine practice, remain controversial 3.
• Patients with high levels of total and conjugated bilirubin or levels of alkaline phosphatase more than 1.5-fold the upper limit of normal should be considered for second-line therapy 6.