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Targeting the gut-liver-immune axis to treat cirrhosis
http://orcid.org/0000-0001-9290-3044Thomas Henry Tranah1, http://orcid.org/0000-0002-8222-4555Lindsey A Edwards1, Bernd Schnabl2, http://orcid.org/0000-0001-6133-4619Debbie Lindsay Shawcross1
Author affiliations
Institute of Liver Studies, Department of Inflammation Biology, School of Immunology and Microbial Sciences, FoLSM, King's College London, London, UK
Medicine, University of California San Diego, San Diego, California, USA
Correspondence to Professor Debbie Lindsay Shawcross, Institute of Liver Studies and Transplantation, King's College London, London WC2R 2LS, UK; [email protected]
Abstract
Cirrhotic portal hypertension is characterised by development of the decompensating events of ascites, encephalopathy, portal hypertensive bleeding and hepatorenal syndrome, which arise in a setting of cirrhosis-associated immune dysfunction (CAID) and define morbidity and prognosis. CAID describes the dichotomous observations that systemic immune cells are primed and display an inflammatory phenotype, while failing to mount robust responses to pathogen challenge. Bacterial infections including spontaneous bacterial peritonitis are common complications of advanced chronic liver disease and can precipitate variceal haemorrhage, hepatorenal syndrome and acute-on-chronic liver failure; they frequently arise from gut-derived organisms and are closely linked with dysbiosis of the commensal intestinal microbiota in advanced chronic liver disease.
Here, we review the links between cirrhotic dysbiosis, intestinal barrier dysfunction and deficits of host-microbiome compartmentalisation and mucosal immune homoeostasis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies targeted at restoring intestinal eubiosis, augmenting gut barrier function and ameliorating the mucosal and systemic immune deficits that characterise and define the course of decompensated cirrhosis.
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http://dx.doi.org/10.1136/gutjnl-2020-320786
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