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Primary biliary cholangitis: Old and novel therapy

      Highlights

      • The first FDA-approved treatment for Primary Biliary Cholangitis was UDCA.
      • Approximatively 30–40% of patients fail to respond to UDCA.
      • A number of options are under investigation as second line treatment.
      • Obeticholic acid is the best promising drug.
      • Other emerging therapies are under evaluation.

      Abstract

      Primary biliary cholangitis (PBC), formerly called primary biliary cirrhosis, is a chronic cholestatic liver disease that progresses slowly to end-stage liver disease. The first Food and Drug Administration (FDA)-approved treatment for PBC was ursodeoxycholic acid (UDCA). This treatment slows the progress of the disease, but approximatively 30–40% of patients fail to respond to UDCA. A number of options are under investigation as second line treatment. Obeticholic acid (OCA), a Farnesoid X Receptor agonist, has been approved in May 2017 by FDA for patients non responders or intolerant to UDCA. The results of a randomized, double blind, phase 3 study of OCA (mg or 10 mg) compared to placebo, showed that approximatively 50% of patients reached a significant reduction in serum alkaline phosphatase, a marker predictive of disease progression, liver transplantation or death. Other emerging therapies include: agents targeting fibrosis, inflammation, or immunological response. Indeed, after 30 years of UDCA therapy as unique choice for PBC patients, a number of targets, derived from a deeper knowledge of the pathophysiology of the disease, has been discovered and they offer different and new therapeutic approaches that are now under evaluation.

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