title: The ischemic liver cirrhosis theory and its clinical implications.
abstract: The canonical pathway theory of cirrhosis addresses inflammation as the main driver of hepatic fibrogenesis in hepatitis, so needing a further hypothesis for etiologies missing inflammation, for which parenchymal extinction is postulated. The present paper reports an alternative hypothesis suggesting a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development, whatever is the aetiology of liver chronic injury. In fact, since chronic liver injury could finally result in endothelial damage and micro-vascular thrombosis, leading to a trigger of inappropriate hepatocyte proliferation and fibrosis, finally cirrhosis development could arise from chronic micro-vascular ischemia. Recently, some important confirmation of this hypothesis has been reported. In fact, in a murine experimental model of congestive hepatopathy, it was found that chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. Furthermore, a study on a murine model of cirrhosis reported enoxaparin to reduce hepatic vascular resistance and portal pressure by having a protective role against fibrogenesis. In conclusion, the hypothesis giving a central role of micro-vascular ischemia in fibrogenesis and cirrhosis development could change the clinical scenario of chronic liver disease and have several main implications on management of various liver disease.
authors: Medicina Interna 1, ARNAS Civico - Di Cristina - Benfratelli, Piazzale Liotti 4, Palermo, Italy; Epatologia e Gastroenterologia, Ospedale Niguarda Ca' Granda, Piazza Ospedale Maggiore 3, 20162 Milano, Italy. Electronic address: mancandrea@libero.it.
authors: Andrea
authors: A
authors: Mancuso
mesh_terms: D000818:Animals; D006502:Budd-Chiari Syndrome / Q000503:physiopathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000503:physiopathology; D006505:Hepatitis / Q000503:physiopathology; D006801:Humans; D007249:Inflammation; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000503:physiopathology* / Q000628:therapy; D051379:Mice; D008833:Microcirculation; D008962:Models, Theoretical; D011169:Portal Vein / Q000503:physiopathology; D013927:Thrombosis / Q000503:physiopathology; D016896:Treatment Outcome
keywords: Anticoagulation; Budd Chiari syndrome; Cirrhosis; Portal vein thrombosis