The brain in acute on chronic liver failure.
Acute-on-chronic liver failure (ACLF) is a newly defined clinical entity with significant morbidity and mortality (~40-90% at 1 year dependent on need for organ support at presentation). It defines a presentation with acute severe liver injury, often with multiorgan dysfunction, on a background of previously known or unknown cirrhosis. In its severest form, it is almost indistinguishable from acute liver failure, as similarly in around 5% may rapidly progress to intracranial hypertension and cerebral oedema culminating in coma and/or death. Our understanding of such cerebral sequelae is currently limited to clinical observation, though our knowledge base is rapidly expanding since recent consensus clinical definition and guidance. Moreover, there are now animal models of ACLF and imaging modalities to better characterize events in the brain that occur with ACLF. However, as yet there has been little in the way of interventional study of this condition which are much needed. In this review we dissect existing clinical and experimental data to better characterise the manifestations of ACLF on the brain and allow for the development of targeted therapy as currently the plethora of existing interventions were designed to treat either the effects of cirrhosis or acute liver injury independently.
Institute for Liver and Digestive Health, Liver Failure Group, UCL Institute of Hepatology, The Royal Free Hospital, Upper Third UCL Medical School, Pond Street, London, NW3 2PF, UK, gavin.wright@btuh.nhs.uk.
Gavin
G
Wright
Yalda
Y
Sharifi
Maria
M
Jover-Cobos
Rajiv
R
Jalan
D065290:Acute-On-Chronic Liver Failure / Q000150:complications / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D003131:Combined Modality Therapy; D019468:Disease Management; D004195:Disease Models, Animal; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D019586:Intracranial Hypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000145:classification; D017628:Microglia / Q000378:metabolism; D059906:Neuroimaging; D018384:Oxidative Stress