title: Inflammation and portal hypertension - the undiscovered country.
abstract: Portal hypertension has traditionally been viewed as a progressive process, involving ultrastructural changes including fibrosis, nodule formation, and vascular thrombosis, leading to increased intrahepatic resistance to flow. However, it is increasingly recognized that a significant component of this vascular resistance results from a dynamic process, regulated by complex interactions between the injured hepatocyte, the sinusoidal endothelial cell, the Kupffer cell and the hepatic stellate cell, which impact on sinusoidal calibre. Recent findings suggest these haemodynamic findings are most marked in patients with superimposed inflammation. The precise mechanisms for vascular dysfunction in cirrhosis with superimposed inflammation remain to be fully elucidated but several studies over the past decade have started to generate the hypothesis that inflammation may be a key mediator of the pathogenesis and severity of portal hypertension in this context. This review provides a comprehensive overview of the biological mechanisms for inflammation playing a key role in the severity of portal hypertension, and illustrates potential novel therapies that act by modifying these processes.
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Campus, London NW3 2PF, United Kingdom.
authors.forename: Gautam
authors.initials: G
authors.lastname: Mehta
authors.affiliation: Laboratory of Experimental Gastroenterology, ULB, Brussels, Belgium; Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Erasme Hospital, ULB, Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Campus, London NW3 2PF, United Kingdom.
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.affiliation: Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi-Sunyer (IDIBAPS), Ciber de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Garcia-Pagan
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, 6431 Fannin Street, MSB 4.234, Houston, TX 77030-1501, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fallon
authors.affiliation: Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Vijay H
authors.initials: VH
authors.lastname: Shah
authors.affiliation: INSERM, U773, Centre de Recherche Biomédicale Bichat-Beaujon CRB3, Paris/Clichy, France; Université Paris-Diderot, Paris 7, UMR-S773, Paris, France; Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Campus, London NW3 2PF, United Kingdom. Electronic address: r.jalan@ucl.ac.uk.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D004932:Esophageal and Gastric Varices / Q000209:etiology; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006801:Humans; D006975:Hypertension, Portal / Q000209:etiology* / Q000503:physiopathology* / Q000628:therapy; D007113:Immunity, Innate; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply / Q000276:immunology / Q000503:physiopathology; D064307:Microbiota; D013152:Splanchnic Circulation; D014655:Vascular Resistance; D014664:Vasodilation
keywords: Cirrhosis; Inflammation; Liver failure; Portal hypertension; Variceal bleeding