- 作者：Karl Oettl ; Ruth Birner-Gruenberger ; Walter Spindelboeck ; Hans Peter Stueger ; Livia Dorn ; Vanessa Stadlbauer ; Csilla Putz-Bankuti ; Peter Krisper ; Ivo Graziadei ; Wolfgang Vogel ; Carolin Lackner ; Rudolf E. Stauber
- 关键词：HMA ; human mercaptalbumin ; HNA1 ; human non-mercaptalbumin1 ; HNA2 ; human non-mercaptalbumin2 ; ACLF ; acute-on-chronic liver failure ; INR ; international normalized ratio ; CRP ; C-reactive protein ; MELD ; Model for End-stage Liver Disease ; HPLC ; high performanc
- 刊名：Journal of Hepatology
- 出版年：2013
- 出版时间：November, 2013
- 年：2013
- 卷：59
- 期：5
- 页码：978-983
- 全文大小：727 K
Background & Aims
Impaired binding function of albumin has been demonstrated in end-stage liver disease. This and other functional disturbances of albumin may be related to oxidative stress which is believed to play an important role in the pathogenesis of liver failure as well as sepsis. The aim of the present study was to relate oxidative modification of albumin to loss of albumin binding function in advanced chronic liver failure and in sepsis.Methods
Patients with decompensated cirrhosis or sepsis and healthy controls were investigated. Three fractions of albumin were separated by chromatography according to the redox state of cysteine-34: non-oxidized human mercaptalbumin, reversibly oxidized human non-mercaptalbumin-1, and irreversibly oxidized human non-mercaptalbumin-2 (HNA2). Binding properties of albumin site II were measured using dansylsarcosine as a ligand.
Results
Both in cirrhotic and septic patients, fractions of oxidized albumin were increased and binding capacity for dansylsarcosine was decreased. Mass spectroscopy confirmed specific oxidation of cysteine-34. In cirrhotic patients, dansylsarcosine binding correlated strongly with liver function parameters and moderately with HNA2. Baseline levels of HNA2 accurately predicted 30-day and 90-day survival in cirrhotic patients and this was confirmed in an external validation cohort.
Conclusions
Our results suggest that oxidative damage impairs binding properties of albumin. In advanced liver disease, reduced binding capacity of albumin site II is mainly related to impaired liver function. The plasma level of HNA2 is closely related to survival and may represent a novel biomarker for liver failure.