Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality.
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 = 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 = 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.


CONCLUSIONS
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.
Jalan
Rajiv
R
Liver Failure Group, Institute of Hepatology, University College London, London, United Kingdom.
Schnurr
Kerstin
K
Mookerjee
Rajeshwar P
RP
Sen
Sambit
S
Cheshire
Lisa
L
Hodges
Stephen
S
Muravsky
Vladimir
V
Williams
Roger
R
Matthes
Gert
G
Davies
Nathan A
NA
D000328:Adult; D000418:Albumins / Q000378:metabolism*; D001665:Binding Sites; D016022:Case-Control Studies; D004578:Electron Spin Resonance Spectroscopy; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008103:Liver Cirrhosis / Q000150:complications / Q000378:metabolism* / Q000401:mortality; D017114:Liver Failure, Acute / Q000209:etiology / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D006435:Renal Dialysis
D000418:Albumins; D028441:F2-Isoprostanes; D008315:Malondialdehyde