Published online Mar 27, 2015. doi: 10.4254/wjh.v7.i3.443
Peer-review started: August 30, 2014
First decision: November 1, 2014
Revised: November 8, 2014
Accepted: November 27, 2014
Article in press: November 27, 2014
Published online: March 27, 2015
This review describes the recent developments in the pathobiology of endothelial dysfunction (ED) in the context of cirrhosis with portal hypertension and defines novel strategies and potential targets for therapy. ED has prognostic implications by predicting unfavourable early hepatic events and mortality in patients with portal hypertension and advanced liver diseases. ED characterised by an impaired bioactivity of nitric oxide (NO) within the hepatic circulation and is mainly due to decreased bioavailability of NO and accelerated degradation of NO with reactive oxygen species. Furthermore, elevated inflammatory markers also inhibit NO synthesis and causes ED in cirrhotic liver. Therefore, improvement of NO availability in the hepatic circulation can be beneficial for the improvement of endothelial dysfunction and associated portal hypertension in patients with cirrhosis. Furthermore, therapeutic agents that are identified in increasing NO bioavailability through improvement of hepatic endothelial nitric oxide synthase (eNOS) activity and reduction in hepatic asymmetric dimethylarginine, an endogenous modulator of eNOS and a key mediator of elevated intrahepatic vascular tone in cirrhosis would be interesting therapeutic approaches in patients with endothelial dysfunction and portal hypertension in advanced liver diseases.
Core tip: Endothelial dysfunction (ED) is a key and early relentless event in patients suffering from gastrointestinal bleeding in cirrhosis and involves in response to both vasoactive and vasoconstrictor substances. The one such vasoactive molecule, nitric oxide (NO) plays a prime role in maintaining normal hepatic vascular function and if there any defect in NO availability leads to ED and portal hypertension (PHT) could be of great utility in preventing and curing complications of PHT.