title: Role of ammonia, inflammation, and cerebral oxygenation in brain dysfunction of acute-on-chronic liver failure patients.
abstract: Hepatic encephalopathy (HE) is a common feature of acute-on-chronic liver failure (ACLF). Although ammonia, inflammation, and cerebral oxygenation are associated with HE in acute liver failure, their roles in ACLF are unknown. The aim of this prospective, longitudinal study was to determine the role of these pathophysiological variables in ACLF patients with and without HE. We studied 101 patients with ACLF admitted to the intensive care unit. Severity of ACLF and HE, arterial ammonia, jugular venous oxygen saturation (JVO2 ), white blood cell count (WCC), and C-reactive protein were measured at days 0, 1, 3, and 7. Patients were followed until death or hospital discharge. Mortality was high (51 patients, 50.5%), especially in patients with HE of whom 35 of 53 (66.0%) died regardless of ACLF severity. At baseline, increased WCC and abnormal JVO2 (high or low) were independent predictors of death. Further deterioration in inflammation, JVO2 , and ammonia were also predictive of mortality. JVO2 deviation and hyperammonemia were associated with the presence and severity of HE; improvement in these parameters was associated with a reduction in HE grade. No direct interaction was observed between these variables in regards to mortality or HE. In conclusion, this study describes potential mechanisms of HE in ACLF indicating that ammonia and abnormal cerebral oxygenation are important. The results suggest that ammonia, JVO2 , and WCC are important prognostic biomarkers and therapeutic targets. The relative roles of these pathophysiological factors in the pathogenesis of HE in ACLF or guiding therapy to improve survival requires future study. Liver Transplantation 22 732-742 2016 AASLD.
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sawhney
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Holland-Fischer
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Matteo
authors.initials: M
authors.lastname: Rosselli
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Rajeshwar P
authors.initials: RP
authors.lastname: Mookerjee
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Banwari
authors.initials: B
authors.lastname: Agarwal
authors.affiliation: Liver Failure Group, Institute for Liver and Digestive Health, University College London, Royal Free Hospital, London, UK.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000150:complications / Q000401:mortality; D000328:Adult; D000641:Ammonia / Q000009:adverse effects* / Q000097:blood; D001158:Arteries / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006501:Hepatic Encephalopathy / Q000097:blood* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications; D007601:Jugular Veins / Q000378:metabolism; D007958:Leukocyte Count; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010092:Oximetry; D010100:Oxygen / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D000641:Ammonia; D002097:C-Reactive Protein; D010100:Oxygen