Novel therapeutic targets in primary biliary cirrhosis

Jessica K. Dyson, Gideon M. Hirschfield, David H. Adams, Ulrich Beuers, Derek A. Mann, Keith Lindor, David E J Jones

Research output: Contribution to journalReview article

65 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)147-158
Number of pages12
JournalNature Reviews Gastroenterology and Hepatology
Volume12
Issue number3
DOIs
StatePublished - Mar 6 2015

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Dyson, J. K., Hirschfield, G. M., Adams, D. H., Beuers, U., Mann, D. A., Lindor, K., & Jones, D. E. J. (2015). Novel therapeutic targets in primary biliary cirrhosis. Nature Reviews Gastroenterology and Hepatology, 12(3), 147-158. https://doi.org/10.1038/nrgastro.2015.12