title: Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.
abstract: Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.
authors.affiliation: Institute of Liver Studies, Kings College Hospital, London, United Kingdom. antoniades@doctors.org.uk
authors.forename: Charalambos G
authors.initials: CG
authors.lastname: Antoniades
authors.forename: Philip A
authors.initials: PA
authors.lastname: Berry
authors.forename: Matthew
authors.initials: M
authors.lastname: Bruce
authors.forename: Timothy J S
authors.initials: TJ
authors.lastname: Cross
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Portal
authors.forename: Munther J
authors.initials: MJ
authors.lastname: Hussain
authors.forename: William
authors.initials: W
authors.lastname: Bernal
authors.forename: Julia A
authors.initials: JA
authors.lastname: Wendon
authors.forename: Diego
authors.initials: D
authors.lastname: Vergani
mesh_terms: D018806:APACHE; D000199:Actins; D000328:Adult; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D003404:Creatinine / Q000097:blood; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood*; D017114:Liver Failure, Acute / Q000097:blood*; D016896:Treatment Outcome; D014809:Vitamin D-Binding Protein / Q000032:analysis*
chemical_list: D000199:Actins; D015415:Biomarkers; D014809:Vitamin D-Binding Protein; D003404:Creatinine; D001663:Bilirubin