Treatment of primary biliary cirrhosis

Introduction: Primary biliary cirrhosis (PBC) is a chronic inflammatory autoimmune disease that mainly targets the cholangiocytes of the interlobular bile ducts in the liver. Inflammation and destruction of the bile ducts lead to decreased bile secretion, retention of toxic substances within the liver, fibrosis, cirrhosis and eventually liver failure, thereby requiring liver transplantation. Several issues - pathogenesis in part unknown, relative rarity and wide range of severity - add to the challenge of designing and executing high-quality clinical trials in PBC. Ursodeoxycholic acid (UDCA) is the only approved drug for the treatment of PBC. Areas covered: This article reviews, in depth, the main features of the disease that are pertinent for the understanding of the current management and the development of new therapies in PBC. The rationales of potential therapeutic medical approaches with farnesoid x receptor, norUDCA, peroxisome proliferator-activated receptor-alpha agonists and budesonide and their place as well their limits are highlighted and critically discussed. A literature search on PubMed has been undertaken and the most relevant references have been considered. Expert opinion: All PBC patients with abnormal liver tests should be treated with UDCA (13 - 15 mg/kg/day) and those with a normal bilirubin level, transaminases and alkaline phosphatase < 1.5 the upper limit of normal within 6 months will continue on UDCA alone. Patients who do not achieve this response and with no or mild bile duct and parenchymal inflammation should receive in addition to UDCA bezafibrate or fenofibrate. Patients with moderate-to-severe cholangitis or hepatitis activity should receive budesonide.