What is Primary Biliary Cholangitis (PBC)?

From the Guidelines

Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disease characterized by the immune system's attack on the small bile ducts in the liver, leading to inflammation, scarring, and potential liver damage or failure if left untreated. This condition predominantly affects women, typically between the ages of 40-60, and its standard treatment involves the use of ursodeoxycholic acid (UDCA) to improve bile flow and reduce inflammation 1. The disease's progression is slow, and with proper treatment, most patients can maintain normal liver function and life expectancy.

Key Characteristics and Treatment

• PBC primarily affects the small bile ducts in the liver, causing inflammation and scarring.
• The standard treatment is ursodeoxycholic acid (UDCA), usually prescribed at a dose of 10 to 15 mg/kg/day in two divided doses, which helps improve bile flow and reduce inflammation 1.
• For patients who don't respond adequately to UDCA, obeticholic acid (Ocaliva) may be considered as a second-line therapy, in combination with UDCA, for patients with an incomplete response or intolerance to UDCA 1.
• Regular monitoring of liver function tests is essential to assess treatment response.

Symptoms and Diagnosis

• Early symptoms often include fatigue, itching (pruritus), and dry eyes/mouth.
• Many patients are asymptomatic and diagnosed through routine blood tests showing elevated alkaline phosphatase levels.
• The disease progresses slowly, and with proper treatment, most patients can maintain normal liver function and life expectancy.

Management Considerations

• Ursodeoxycholic acid should be given lifelong after liver transplantation to all patients with primary biliary cholangitis to prevent recurrence 1.
• The choice of immunosuppressive regimen should consider medication adherence, as this is one of the most important risks for acute rejection 1.
• Mental health should be screened, and psychological therapies should be provided to patients experiencing common feelings such as reactive depression or anxiety 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. The answer to what Primary Biliary Cholangitis (PBC) is, is not directly stated in the provided drug labels.

• Definition of PBC is not provided in the labels.
• The labels only mention that OCALIVA is used to treat PBC. 2

From the Research

Definition and Characteristics of Primary Biliary Cholangitis (PBC)

• Primary Biliary Cholangitis (PBC) is a chronic autoimmune liver disorder characterized by progressive cholestatic that, if untreated, can progress to liver fibrosis, cirrhosis, and liver decompensation requiring liver transplant 3.
• PBC is an uncommon, chronic, cholangiopathy of autoimmune origin and unknown etiology characterized by positive anti-mitochondrial autoantibodies (AMA), female preponderance, and progression to cirrhosis if left untreated 4.
• The disease affects mainly women and is often discovered through abnormal alkaline phosphatase (ALP) activity, and is confirmed when anti-mitochondrial antibodies (AMA) are present 5.

Pathogenesis and Risk Factors

• Although the pathogenesis of the disease is multifactorial, there is a consensus that individuals with a genetic predisposition develop the disease in the presence of specific environmental triggers 3.
• A dysbiosis of intestinal microbiota is increasingly considered among the potential pathogenic factors 3.
• Cigarette smoking, immune dysregulation, nail polish, urinary tract infections, and low socioeconomic status have been implicated but none have been confirmed 5.
• Genome-wide association studies (GWAS) have disclosed strong associations between certain human leukocyte antigen (HLA) alleles and PBC 5.

Diagnosis and Treatment

• The diagnosis is based on AMA- or PBC-specific anti-nuclear antibody (ANA)-positivity in the presence of a cholestatic biochemical profile, histologic confirmation being mandatory only in seronegative cases 4.
• Ursodeoxycholic acid (UDCA) remains the initial treatment of choice for PBC, with obeticholic acid and fibrates (off-label therapy) reserved as add-on therapy for the management of inadequate responders or those with UDCA intolerance 6.
• Obeticholic acid (OCA) has been examined in PBC patients with inadequate response to UDCA and shown promising results, particularly in reducing serum alkaline phosphatase (ALP) 5, 7.