Description

• A chronic and progressive T-cell–mediated liver disease characterized by granulomatous destruction of intrahepatic bile ducts (1)
• If untreated, primary biliary cirrhosis (PBC) can lead to cirrhosis, portal hypertension, liver failure, and the need for possible liver transplantation (2).

Epidemiology

• PBC primarily affects women; female:male ratio of 8 to 10:1 (1,2)
• Peak age: 40 to 60 years; rare in children (2)

Prevalence

• Rare, present in all parts of the world and all races and nationalities; more common in Northern European countries and in the Northern United States
• Annual incidence: 0.7 to 49/1,000,000
• Prevalence: 4 to 14/100,000 (2)

Etiology and Pathophysiology

• PBC is caused by a T-cell–mediated attack on biliary epithelial cells primarily small, intrahepatic bile ducts.
• Destruction causes cholestasis, which can lead to cirrhosis and liver failure.
• Bile duct destruction leads to retained bile acids and foamy hepatocyte degeneration (2).

Genetics

• Monozygotic twin concordance as high as 63% (2)
• Family predisposition: 1–6% of individuals with PBC have at least one family member with the disease (3).
• Having a first-degree relative with PBC significantly increases the risk, odds ratio (OR) of 11 (1).

Risk Factors

• PBC primarily occurs in genetically susceptible people exposed to specific environmental triggers (1,2,3).
• Some studies have suggested that infection (bacterial and viral) may be a trigger.
• Clusters of cases suggest a possible role of a range of environmental toxins.
• Smoking increases risk of progression of fibrosis.
• PBC risk is increased following pregnancy-related pruritus or cholestasis in genetically susceptible individuals (1).

Commonly Associated Conditions

• PBC associated with: Sjögren syndrome, scleroderma, rheumatoid arthritis, lupus, autoimmune thyroiditis, Raynaud phenomenon, sarcoidosis, pulmonary fibrosis, polymyositis, celiac disease, and ulcerative colitis (2)
• 53% have one or more concurrent autoimmune conditions (1,2).
• Overlap syndrome with autoimmune hepatitis in 5–19%. Diagnosis is difficult and prognosis worse (1).
• Cirrhotic PBC increases relative risk of hepatocellular carcinoma (HCC). HCC occurs 1–6% of patients with PBC per year (1).