Abstract
Primary biliary cholangitis (PBC), formally known as primary biliary cirrhosis, is a chronic cholestatic liver disease that predominantly affects adult women of all ages, more commonly in the middle years of life. It presents as a chronic nonsuppurative destructive cholangitis with granuloma formation in the liver; degeneration and necrosis of biliary epithelial cells (BECs) elicit destructive changes and disappearance of small- or medium-sized intrahepatic bile ducts, leading to chronic and progressive cholestasis. Although the etiology of PBC has not been fully elucidated, robust evidence indicates that autoimmune reactions against intrahepatic BECs play a critical role in the pathogenesis of the disease. Indeed, PBC is considered a model autoimmune disease because of detection of disease-specific autoantibodies (i.e., antimitochondrial autoantibodies), dense infiltration of mononuclear cells into the bile ducts, and a high prevalence of associated autoimmune diseases. Whereas in most cases the disease is incidentally detected during random blood testing, a substantial number of patients experience a variety of symptoms, including pruritus, fatigue, dry eyes, dry mouth, and abdominal pain. Other autoimmune diseases such as rheumatoid arthritis, Sjogren’s syndrome, and chronic thyroiditis frequently coexist in patients with PBC. Jaundice and other decompensating events of the liver develop as progressive features, eventually resulting in liver failure and the need for liver transplantation (LT). Until 2016, ursodeoxycholic acid (UDCA) had been the only approved drug for PBC and clinical trials demonstrated that the administration of UDCA can extend LT-free survival. Unfortunately, 30%–50% of the patients with PBC are refractory to UDCA. In 2016, obeticholic acid (OCA), a farnesoid X receptor agonist, was approved for UDCA-refractory or UDCA-intolerant patients; however, the efficacy and safety of OCA are still unsatisfactory. Fibrates, including bezafibrate and fenofibrate, are available as off-label therapy for patients with insufficient response to UDCA, and their use is endorsed by both American and European guidelines.1,2 Several other drugs with different mechanisms of action are currently under investigation. An individualized treatment strategy based on risk stratification for disease progression should be a goal in the treatment of PBC.