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Inflammation is also key to the pathobiology of portal hypertension. This study aims to define the relationship between systemic and hepatic haemodynamics in patients with <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Sixty patients with alcoholic cirrhosis were prospectively enrolled \u2013 stable cirrhosis (<jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content>,<jats:italic> n<\/jats:italic>\u00a0=\u00a027), acute decompensation without <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>,<jats:italic> n<\/jats:italic>\u00a0=\u00a014) and <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0=\u00a019) \u2013 and managed with standard therapy. Systemic and hepatic haemodynamic studies were performed, and patients were followed up for 3\u00a0months. Plasma norepinephrine, cytokine profile, nitrate\/nitrite and malondialdehyde levels were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Three\u2010month mortality was as follows: <jats:styled-content style=\"fixed-case\">SC<\/jats:styled-content> \u2013 none; <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content> \u2013 14%; <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> \u2013 47.2% (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Mean arterial pressure was lowest in the <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> group (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> patients had significantly higher hepatic vein pressure gradient (<jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content>), while the hepatic blood flow was markedly reduced with an increase in intrahepatic resistance, which predicted mortality (<jats:styled-content style=\"fixed-case\">AUROC<\/jats:styled-content>: 0.87, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001). In <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content>, the severity of intrahepatic resistance correlated with markers of inflammatory response, norepinephrine levels, creatinine levels and severity of encephalopathy. Modelling data showed that the high norepinephrine levels in <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> may contribute to the right shift of the <jats:styled-content style=\"fixed-case\">HVPG<\/jats:styled-content>\u2013hepatic blood flow relationship and its levels correlated with inflammatory markers and mortality (<jats:styled-content style=\"fixed-case\">AUROC<\/jats:styled-content>: 0.90; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The disturbances in systemic and hepatic haemodynamics in alcohol\u2010related <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> are associated with dysregulated inflammation, multi\u2010organ failure and marked activation of the sympathetic nervous system. These abnormalities predict high mortality rates in alcohol\u2010related <jats:styled-content style=\"fixed-case\">ACLF<\/jats:styled-content> patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.12559","type":"journal-article","created":{"date-parts":[[2014,4,4]],"date-time":"2014-04-04T12:44:44Z","timestamp":1396615484000},"page":"724-734","source":"Crossref","is-referenced-by-count":99,"title":["Systemic inflammation is associated with increased intrahepatic resistance and mortality in alcohol\u2010related acute\u2010on\u2010chronic liver failure"],"prefix":"10.1111","volume":"35","author":[{"given":"Gautam","family":"Mehta","sequence":"first","affiliation":[{"name":"UCL Institute for Liver and Digestive Health Division of Medicine UCL Medical School Royal Free Hospital Rowland Hill Street NW3 2PF London"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeshwar P","family":"Mookerjee","sequence":"additional","affiliation":[{"name":"UCL Institute for Liver and 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