Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n โซุโฌ 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute-on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve โซุโฌ 0.8). No change in the patients' albumin function was observed following MARS therapy. A significant negative correlation between IMAR and the fatty acid binding coefficients for sites 1 and 2 (P < 0.001 for both) was observed, indicating possible sites of association on the protein.
Conclusion:
The results of this study suggests marked dysfunction of albumin function in advanced cirrhosis and provide further evidence for damage to the circulating albumin, which is not reversed by MARS therapy. IMAR correlates with disease severity and may have prognostic use in acute-on-chronic liver failure. (HEPATOLOGY 2009;50:555-564.)
See Editorial on Page 355
A lbumin is the major plasma protein and constitutes around 50% of the cell free protein in healthy individuals. It is produced exclusively in the liver, and therefore its concentration is reduced during hepatic dysfunction. 1 Following the Cochrane meta-analysis describing potential harmfully effect of albumin infusion in critically ill patients, there has been a reexamination of the use of albumin infusions for volume replacement. However, the results of the recently published SAFE study have provided new data confirming the safety of albumin infusion in critically ill patients. 2,3 Liver failure results in multiple organ dysfunction, and mortality rates without liver transplantation remain unacceptably high. 4 However, recovery is associated with complete reversal of multiorgan dysfunction. At present, in patients with cirrhosis, albumin is used mainly to replenish the circulating volume. With increasing severity of cirrhosis, there is a progressive increase in cardiac output, which is associated with a progressive reduction in individual organ blood flow. This peculiar circulatory disturbance is thought to occur as a result of splanchnic Abbreviations: ACLF, acute-on-chronic liver failure; AUROC, area under the receiver operating curve; EPR, electron paramagnetic resonance; IMA, ischemiamodified albumin; IMAR, IMA/albumin ratio; MARS, Molecular Adsorbents Recirculating System; MELD, model of end-stage liver disease.