title: Hepatic erythropoietin response in cirrhosis. A contemporary review.
abstract: The main function of erythropoietin (EPO) is to maintain red blood cell mass, but in recent years, increasing evidence has suggested a wider biological role not solely related to erythropoiesis, e.g. angiogenesis and tissue protection. EPO is produced in the liver during fetal life, but the main production shifts to the kidney after birth. The liver maintains a production capacity of up to 10% of the total EPO synthesis in healthy controls, but can be up-regulated to 90-100%. However, the hepatic EPO synthesis has been shown not to be adequate for correction of anemia in the absence of renal-derived EPO. Elevated circulating EPO has been reported in a number of diseases, but data from cirrhotic patients are sparse and the level of plasma EPO in patients with cirrhosis is controversial. Cirrhosis is characterized by liver fibrosis, hepatic dysfunction and the release of proinflammatory cytokines, which lead to arterial hypotension, hepatic nephropathy and anemia. An increase in EPO due to renal hypoperfusion, hypoxia and anemia or an EPO-mediated hepato-protective and regenerative mechanism is plausible. However, poor hepatic synthesis capacity, a decreasing co-factor level and inflammatory feedback mechanisms may explain a potential insufficient EPO response in end-stage cirrhosis. Finally, the question remains as to whether a potential increase in EPO production in certain stages of cirrhosis originates from the kidney or liver. This paper aims to review contemporary aspects of EPO relating to chronic liver disease.
authors.affiliation: a Department of Clinical Physiology and Nuclear Medicine, Center of Functional and Diagnostic Imaging and Research 260 , Hvidovre Hospital, University of Copenhagen ;
authors.forename: Louise Madeleine
authors.initials: LM
authors.lastname: Risør
authors.affiliation: b Department of Clinical Biochemistry, Hvidovre; Faculty of Health Sciences , University of Copenhagen ;
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.affiliation: c Department of Neuroanaesthesia, the Neuroscience Centre , University Hospital of Copenhagen (Rigshospitalet), and ;|d Department of Neuroscience and Pharmacology, the Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
authors.affiliation: a Department of Clinical Physiology and Nuclear Medicine, Center of Functional and Diagnostic Imaging and Research 260 , Hvidovre Hospital, University of Copenhagen ;
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
mesh_terms: D000818:Animals; D016232:Endothelins / Q000502:physiology; D004921:Erythropoietin / Q000502:physiology*; D006439:Hemodynamics; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology
chemical_list: D016232:Endothelins; D004921:Erythropoietin; D009569:Nitric Oxide
keywords: Anemia; angiogenesis; chronic inflammation; cirrhosis; hemodynamic disturbances; hepatic nephropathy; hypoxia; tissue protection; vasoconstriction; vasodilation