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Experimental and Investigational Targeted Therapies for the Management of Fibrosis in NASH: An Update
Author(s) -
Tsipora M. Huisman,
Douglas T. Dieterich,
Scott L. Friedman
Publication year - 2021
Publication title -
journal of experimental pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.555
H-Index - 12
ISSN - 1179-1454
DOI - 10.2147/jep.s265286
Subject(s) - steatohepatitis , cirrhosis , medicine , hepatic stellate cell , fibrosis , fatty liver , hepatic fibrosis , liver disease , viral hepatitis , clinical trial , liver transplantation , chronic liver disease , disease , bioinformatics , immunology , transplantation , biology
There have been major advances in the treatment of HBV and HCV with anti-viral treatments, which is reducing the prevalence of fibrosis due to these viruses and obviating the need for anti-fibrotic therapies in these diseases. At the same time, however, the prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing, of which a substantial fraction of patients have non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis. Accordingly, NASH is emerging as the leading indication for liver transplantation in North America and Europe. Progress in uncovering pathogenic determinants of fibrosis in NASH include metabolic dysregulation in hepatocytes that induce inflammation and cytokine secretion leading to cell injury and apoptosis, among others. These pathogenic events converge upon hepatic stellate cells, which are the primary fibrogenic cell in liver, and represent a target of new therapeutic candidates that are currently being evaluated in animal models and clinical trials. This review highlights key experimental and investigational therapies for NASH fibrosis, whose evaluation will be accelerated as new non-invasive markers of fibrosis are established. While no drugs are approved yet for NASH fibrosis, there is growing optimism that new pharmacotherapies are likely to emerge within the next 3 years that will favorably alter the natural history of disease.

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