title: Advances in pharmacotherapy for primary biliary cirrhosis.
abstract: BACKGROUND
  Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle-aged women characterized by progressive nonsuppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury and ultimately end-stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one-third of patients are unresponsive.
  
  
  METHODS
  Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for nonresponders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids.
  
  
  CONCLUSIONS
  We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide and obeticholic acid offer encouragement for nonresponders to UDCA.
authors.affiliation: Humanitas Clinical and Research Center, Liver Unit and Center for Autoimmune Liver Diseases , Rozzano (MI) , Italy.
authors.forename: Hani S
authors.initials: HS
authors.lastname: Mousa
authors.forename: Ana
authors.initials: A
authors.lastname: Lleo
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Bowlus
authors.forename: Merril Eric
authors.initials: ME
authors.lastname: Gershwin
mesh_terms: D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000473:pathology; D001647:Bile Acids and Salts / Q000378:metabolism; D019819:Budesonide / Q000627:therapeutic use; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D058625:End Stage Liver Disease / Q000517:prevention & control; D005260:Female; D058607:Fibric Acids / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000378:metabolism; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000473:pathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D015398:Signal Transduction; D017211:Treatment Failure; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D001647:Bile Acids and Salts; D058607:Fibric Acids; D018160:Receptors, Cytoplasmic and Nuclear; C464660:obeticholic acid; D002635:Chenodeoxycholic Acid; D019819:Budesonide; D014580:Ursodeoxycholic Acid
keywords: biologics; farnesoid X receptor agonists; primary biliary cirrhosis; ursodeoxycholic acid