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      Pathobiology of liver fibrosis: a translational success story.

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          Abstract

          Reversibility of hepatic fibrosis and cirrhosis following antiviral therapy for hepatitis B or C has advanced the prospect of developing antifibrotic therapies for patients with chronic liver diseases, especially non-alcoholic steatohepatitis. Mechanisms of fibrosis have focused on hepatic stellate cells, which become fibrogenic myofibroblasts during injury through 'activation', and are at the nexus of efforts to define novel drug targets. Recent studies have clarified pathways of stellate cell gene regulation and epigenetics, emerging pathways of fibrosis regression through the recruitment and amplification of fibrolytic macrophages, nuanced responses of discrete inflammatory cell subsets and the identification of the 'ductular reaction' as a marker of severe injury and repair. Based on our expanded knowledge of fibrosis pathogenesis, attention is now directed towards strategies for antifibrotic therapies and regulatory challenges for conducting clinical trials with these agents. New therapies are attempting to: 1) Control or cure the primary disease or reduce tissue injury; 2) Target receptor-ligand interactions and intracellular signaling; 3) Inhibit fibrogenesis; and 4) Promote resolution of fibrosis. Progress is urgently needed in validating non-invasive markers of fibrosis progression and regression that can supplant biopsy and shorten the duration of clinical trials. Both scientific and clinical challenges remain, however the past three decades of steady progress in understanding liver fibrosis have contributed to an emerging translational success story, with realistic hopes for antifibrotic therapies to treat patients with chronic liver disease in the near future.

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          Author and article information

          Journal
          Gut
          Gut
          1468-3288
          0017-5749
          May 2015
          : 64
          : 5
          Affiliations
          [1 ] Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
          Article
          gutjnl-2014-306842 NIHMS700801
          10.1136/gutjnl-2014-306842
          4477794
          25681399
          a153b37a-93ea-46c6-968b-00dd28354ab8
          Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

          CIRRHOSIS,EXTRACELLULAR MATRIX,FATTY LIVER,HEPATIC FIBROSIS,HEPATIC STELLATE CELL

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