Human Nonmercaptalbumin-2: A Novel Prognostic Marker in Chronic Liver Failure

Albumin is the major plasma protein with several important biological functions. Various disturbances of albumin function have been demonstrated in end-stage liver disease. These functional disturbances may be related to oxidative modifications of albumin at cysteine-34, including the irreversibly oxidized human nonmercaptalbumin-2 (HNA2). The aim of the present study was to relate oxidative modification of albumin to short-term prognosis in chronic liver failure. Patients with advanced cirrhosis (N=39), acute-on-chronic liver failure (N=15), and healthy controls (N=15) were investigated. Three fractions of albumin were separated by high performance liquid chromatography according to the redox state of cysteine-34. The HNA2 fraction was markedly increased in cirrhotic patients vs. controls and correlated with the degree of chronic liver failure as well as laboratory parameters of liver dysfunction. The HNA2 level tended to be a better predictor of short-term mortality than the model for end stage liver disease with respect to both 30-day mortality (area under the receiver operating characteristic curve [AUROC] 0.87 vs. 0.81, NS) and 90-day mortality (AUROC 0.87 vs. 0.82, NS). In multivariate analysis of prognostic variables, HNA2 was the only remaining predictor of 90-day mortality. Our results suggest that HNA2, a marker of chronic oxidative stress, is related to liver dysfunction and mortality in cirrhosis and may represent a novel biomarker of chronic liver failure.