What is Primary Biliary Cholangitis (PBC)?

From the Guidelines

The first-line treatment for Primary Biliary Cholangitis (PBC) is ursodeoxycholic acid (UDCA), which should be prescribed at a dose of 13-15 mg/kg/day and taken daily indefinitely, as it has been shown to improve liver function and reduce the risk of disease progression 1.

Treatment Overview

PBC is an autoimmune liver disease that primarily affects the bile ducts in the liver. The goal of treatment is to slow disease progression, improve symptoms, and prevent complications.

• UDCA is the primary treatment for PBC, and it works by improving bile flow, reducing inflammation, and protecting liver cells from damage caused by toxic bile acids.
• For patients who do not respond adequately to UDCA (about 40%), obeticholic acid (Ocaliva) may be added at a starting dose of 5 mg daily, potentially increasing to 10 mg daily if tolerated 1.

Monitoring and Management

Management of PBC also includes:

• Monitoring liver function tests every 3-6 months to assess treatment response and disease progression.
• Addressing symptoms like fatigue and pruritus, which may require medications like cholestyramine or rifampicin.
• Screening for complications such as osteoporosis and fat-soluble vitamin deficiencies.

Risk Stratification

The GLOBE score and UK-PBC score are useful tools for risk stratification in patients with PBC, as they can accurately predict the risk of major outcomes, including liver-related death, liver transplantation, or bilirubin >100 µmol/L 1.

• The GLOBE score includes age, total bilirubin, alkaline phosphatase, albumin, and platelet count, and has been shown to accurately predict LT-free survival at 5 and 10 years.
• The UK-PBC score includes baseline albumin and platelet count, and bilirubin, AST or ALT, and ALP 12 months after starting UDCA, and has been shown to accurately predict the risk of major outcomes at 5,10, and 15 years.

Disease Progression

Early diagnosis and treatment are crucial in PBC, as they can significantly slow disease progression and improve long-term outcomes, potentially delaying or preventing the need for liver transplantation in advanced cases 1.

• On-treatment liver stiffness measurement (LSM) by transient elastography (TE) is indicated during follow-up, as worsening of LSM predicts patient outcomes.
• An increase of 2.1 kPa/year in LSM by TE was associated with a 8.4-fold increase in the risk of adverse outcomes.

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. The answer to PBC is that Obeticholic acid (OCALIVA) is used to treat primary biliary cholangitis (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.
  • It is not known if OCALIVA improves survival or symptoms of PBC.
  • OCALIVA can cause serious side effects, including worsening of liver problems or liver failure 2.

From the Research

Definition and Diagnosis 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.
• Diagnosis of PBC is based on the presence of antimitochondrial antibodies (AMA) or specific antinuclear antibodies, and a cholestatic biochemical profile, while biopsy is recommended only in selected cases 3.

Treatment Options for PBC

• The first-line therapy for PBC is ursodeoxycholic acid (UDCA), which has been proven to normalize serum markers of liver dysfunction, halt histologic disease progression, and lead to a prolongation of transplant-free survival 4, 5.
• Obeticholic acid (OCA) is the only registered agent for second-line treatment in UDCA-non responders, and has been shown to decrease serum alkaline phosphatase, a marker for long-term survival 4, 6.
• Fibrates, including fenofibrate and bezafibrate, have also been studied as potential second-line therapies, but more robust studies are needed to confirm their benefits 7.

Management of Patients with Incomplete Response to Therapy

• Patients with PBC should be assessed after 12 months of treatment with UDCA for biochemical markers of response, and those 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 5.
• Incomplete responders should be considered for second-line therapies with OCA or fibrates in addition to continued treatment with UDCA 5.
• Patients with PBC should be followed up for life to monitor their response to therapy and adjust treatment as needed 5.