Gut-liver axis signaling in portal hypertension.

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    • Source:
      Publisher: Baishideng Publishing Group Country of Publication: United States NLM ID: 100883448 Publication Model: Print Cited Medium: Internet ISSN: 2219-2840 (Electronic) Linking ISSN: 10079327 NLM ISO Abbreviation: World J Gastroenterol Subsets: MEDLINE
    • Publication Information:
      Publication: 2014- : Pleasanton, CA : Baishideng Publishing Group
      Original Publication: Beijing : WJG Press, c1998-
    • Subject Terms:
    • Abstract:
      Portal hypertension (PHT) in advanced chronic liver disease (ACLD) results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition (structural component) and intrahepatic vasoconstriction (functional component). PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding. Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns (PAMPs) that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways. Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability: The intestinal barrier function is affected by impaired microcirculation, neoangiogenesis, and abnormal vascular and mucosal permeability. The close bidirectional relationship between the gut and the liver has been termed "gut-liver axis". Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function, intestinal barrier integrity, as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects. The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments, however, further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed. In this review, we summarize the clinical impact of PHT on the course of liver disease, discuss the underlying pathophysiological link of PHT to gut-liver axis signaling, and provide insight into molecular mechanisms that may represent novel therapeutic targets.
      Competing Interests: Conflict-of-interest statement: No financial support has been received for this review. Benedikt Simbrunner has received travel support from AbbVie and Gilead; Mattias Mandorfer has served as a speaker and/or consultant and/or advisory board member for AbbVie, Bristol-Myers Squibb, Gilead, W.L. Gore & Associates and Janssen; Michael Trauner received speaker fees from BMS, Falk Foundation, Gilead and MSD; advisory board fees from Albireo, Falk Pharma GmbH, Genfit, Gilead, Intercept, MSD, Novartis, Phenex and Regulus. He further received travel grants from Abbvie, Falk, Gilead and Intercept and unrestricted research grants from Albireo, Cymabay, Falk, Gilead, Intercept, MSD and Takeda. Thomas Reiberger received grant support from Abbvie, Boehringer-Ingelheim, Gilead, MSD, Philips Healthcare, Gore; speaking honoraria from Abbvie, Gilead, Gore, Intercept, Roche, MSD; consulting/advisory board fee from Abbvie, Bayer, Boehringer-Ingelheim, Gilead, MSD, Siemens; and travel support from Boehringer-Ingelheim, Gilead and Roche.
      (©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.)
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    • Contributed Indexing:
      Keywords: Bacterial translocation; Cirrhosis; Farnesoid X receptor; Gut-liver axis; Intestinal barrier; Portal hypertension
    • Accession Number:
      0 (Pathogen-Associated Molecular Pattern Molecules)
    • Publication Date:
      Date Created: 20191030 Date Completed: 20200226 Latest Revision: 20200226
    • Publication Date:
      20240628
    • Accession Number:
      PMC6815800
    • Accession Number:
      10.3748/wjg.v25.i39.5897
    • Accession Number:
      31660028