What are the key points of Primary Biliary Cholangitis (PBC)?

From the Guidelines

Primary Biliary Cholangitis (PBC) patients should be treated with ursodeoxycholic acid (UDCA) at a dose of 13-15 mg/kg/day as first-line therapy, with the goal of improving morbidity, mortality, and quality of life. This recommendation is based on the British Society of Gastroenterology/UK-PBC guidelines for the treatment and management of PBC, which emphasize the importance of UDCA therapy in all patients with PBC 1. The guidelines suggest that UDCA should be initiated promptly upon diagnosis, with a target of 90% of patients receiving therapy at an adequate dose or being documented as intolerant.

Key Points in PBC Management

• All patients with suspected PBC should undergo an abdominal ultrasound as part of their baseline assessment to exclude alternative aetiologies for cholestasis 1.
• Individualized risk stratification using biochemical response indices is recommended after 1 year of UDCA therapy to identify patients at risk of progressive disease 1.
• Patients should be evaluated for the presence of symptoms, particularly fatigue and itch, to highlight the impact on quality of life and ensure appropriate investigation and treatment 1.
• Regular monitoring of liver biochemistry every 3-6 months is essential to assess treatment response and identify potential complications early.

Treatment and Monitoring

• UDCA at 13-15 mg/kg/day is recommended for first-line use in all patients with PBC, with a goal of achieving a biochemical response and improving quality of life 1.
• Patients with inadequate response to UDCA may require second-line therapy, such as obeticholic acid (OCA), and should be discussed with a hepatologist linked to a liver transplant center 1.
• Patients should be screened for complications, including pruritus, fatigue, osteoporosis, fat-soluble vitamin deficiencies, and portal hypertension, to prevent or delay the need for liver transplantation.

From the FDA Drug Label

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 OCALIVA is contraindicated in PBC patients with decompensated cirrhosis, a prior decompensation event, or with compensated cirrhosis who have evidence of portal hypertension Permanently discontinue OCALIVA in patients who develop laboratory or clinical evidence of hepatic decompensation; have compensated cirrhosis and develop evidence of portal hypertension; or experience clinically significant hepatic adverse reactions while on treatment

Key Points for Primary Biliary Cholangitis (PBC):

• 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.
• Warnings and Precautions: Hepatic decompensation and failure, sometimes fatal or resulting in liver transplant, have been reported with OCALIVA treatment in PBC patients with either compensated or decompensated cirrhosis 2.
• Indications and Usage: OCALIVA is indicated for the treatment of adult patients with primary biliary cholangitis (PBC) without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension 2.
• Dosage and Administration: The recommended starting dosage of OCALIVA is 5 mg once daily for the first 3 months, and may be increased to a maximum dosage of 10 mg once daily 2.

From the Research

Primary Biliary Cholangitis (PBC) Overview

• Primary Biliary Cholangitis (PBC) is a chronic liver disease characterized by the destruction and inflammation of the intrahepatic bile ducts 3.
• The disease is often discovered through abnormal alkaline phosphatase (ALP) activity and is confirmed when anti-mitochondrial antibodies (AMA) are present 3.
• PBC can progress to cirrhosis and end-stage liver disease, with hepatocellular carcinoma (HCC) developing in up to 3.5% of PBC patients 3.

Treatment of PBC

• Ursodeoxycholic acid (UDCA) is the first-line therapy for PBC, 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.
• However, 30-40% of patients do not respond to UDCA, and these patients are at high risk for serious complications 4, 3.
• Obeticholic acid (OCA) is a second-line treatment for PBC patients who do not respond to UDCA, which has been shown to improve surrogate markers of prognosis in PBC 5, 6, 4.
• OCA has been proven to increase the hepatic transport of conjugated bile acids, reducing the time that potentially toxic bile acids reside in the liver 6.

Mechanism of Action of OCA

• OCA is a highly potent farnesoid X receptor (FXR) agonist, which activates FXR leading to decreased bile acid synthesis, inflammation, and fibrosis of the liver 7.
• The activation of FXR by OCA results in the improvement of liver function and the reduction of serum alkaline phosphatase (ALP) levels 6, 3, 7.

Adverse Effects of OCA

• The most clinically relevant adverse effect of OCA is dose-related pruritus 5, 7.
• Other adverse effects of OCA may include increased hepatic blood perfusion and unidirectional uptake clearance of conjugated bile acids 6.

Clinical Use of OCA

• OCA is approved by the US FDA as a second-line treatment for PBC patients who do not respond to UDCA 7.
• The goal of therapy with OCA should be the normalization of ALP and bilirubin below 0.6 the upper limit of normal 5.
• 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 5.