title: Novel therapeutic targets in primary biliary cirrhosis.
abstract: Primary biliary cirrhosis (PBC) is a chronic immune-mediated liver disease characterized by progressive cholestasis, biliary fibrosis and eventually cirrhosis. It results in characteristic symptoms with marked effects on life quality. The advent of large patient cohorts has challenged the view of PBC as a benign condition treated effectively by the single licensed therapy-ursodeoxycholic acid (UDCA). UDCA nonresponse or under-response has a major bearing on outcome, substantially increasing the likelihood that liver transplantation will be required or that patients will die of the disease. In patients with high-risk, treatment-unresponsive or highly symptomatic disease the need for new treatment approaches is clear. Evolution in our understanding of disease mechanisms is rapidly leading to the advent of new and re-purposed therapeutic agents targeting key processes. Notable opportunities are offered by targeting what could be considered as the 'upstream' immune response, 'midstream' biliary injury and 'downstream' fibrotic processes. Combination therapy targeting several pathways or the development of novel agents addressing multiple components of the disease pathway might be required. Ultimately, PBC therapeutics will require a stratified approach to be adopted in practice. This Review provides a current perspective on potential approaches to PBC treatment, and highlights the challenges faced in evaluating and implementing those treatments.
authors: Institute of Cellular Medicine, 3rd Floor William Leech Building, Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Jessica K
authors: JK
authors: Dyson
authors: Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Wolfson Drive, Birmingham B15 2TT, UK.
authors: Gideon M
authors: GM
authors: Hirschfield
authors: Centre for Liver Research, NIHR Biomedical Research Unit, University of Birmingham, Wolfson Drive, Birmingham B15 2TT, UK.
authors: David H
authors: DH
authors: Adams
authors: Department of Gastroenterology &Hepatology, Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, G4-216, University of Amsterdam, PO Box 22600, NL-1100 DD, Amsterdam, Netherlands.
authors: Ulrich
authors: U
authors: Beuers
authors: Institute of Cellular Medicine, 3rd Floor William Leech Building, Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: Derek A
authors: DA
authors: Mann
authors: College of Health Solutions, Arizona State University, 550 North 3rd Street, Phoenix, AZ 85004, USA.
authors: Keith D
authors: KD
authors: Lindor
authors: Institute of Cellular Medicine, 3rd Floor William Leech Building, Medical School, Framlington Place, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors: David E J
authors: DE
authors: Jones
mesh_terms: D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D002779:Cholestasis / Q000188:drug therapy; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy*; D058990:Molecular Targeted Therapy / Q000379:methods* / Q000639:trends; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid
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