HMOX1 and portal hypertension: Indeed, HO-1 overexpression significantly exacerbates liver fibrosis and portal hypertension induced by chronic BDL in rats.25, 33, 34 Further, and in agreement with our results, chronic HO-1 overexpression directly promotes hepatic iron accumulation in BDL rats,25, 37 whereas iron chelation diminishes liver fibrosis.37 We found that RIP3−/− primary hepatocytes displayed increased iron levels compared with WT hepatocytes, being iron content modulated by HO-1 activity.