Ischaemia-modified albumin: a marker of bacterial infection in hospitalized patients with cirrhosis.
OBJECTIVE
Patients with cirrhosis present structural changes of human serum albumin (HSA) affecting non-oncotic functions. Ischaemia-modified albumin (IMA), which reflects the capacity to bind cobalt, has been associated to patient mortality during acute-on-chronic liver failure. This study aimed to assess whether circulating IMA is elevated in advanced cirrhosis and its relationship with severity of cirrhosis and specific complications.


METHODS
A total of 127 cirrhotic patients hospitalized for an acute complication of the disease and 44 healthy controls were enrolled. Plasma IMA and IMA to albumin ratio (IMAr) were measured with a cobalt-binding assay. HSA isoforms carrying post-transcriptional molecular changes were assessed with HPLC-ESI-MS. The effect of endotoxemia on IMA was evaluated in rats with CCl4 -cirrhosis.


RESULTS
IMA/IMAr is significantly higher in cirrhotic patients than in controls, but no correlations were found with prognostic scores. IMA did not correlate with the altered HSA isoforms. Ascites, renal impairment and hepatic encephalopathy did not influence IMA/IMAr levels. In contrast, IMA/IMAr is significantly higher in infected than non-infected patients. ROC curves showed that IMA/IMAr had similar discriminating performances for bacterial infection as C-reactive protein (CRP). Moreover, CRP and IMA were independently associated with bacterial infection. Consistently, endotoxin injection significantly increased IMA in cirrhotic, but not in healthy rats.


CONCLUSIONS
IMA is elevated in patients with advanced cirrhosis. The IMA level does not correlate with disease severity scores, but it is specifically associated to bacterial infection, showing a discriminating performance similar to CRP. Further investigations to assess IMA as a novel diagnostic test for bacterial infection are advocated.
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Ferdinando A
FA
Giannone
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Marco
M
Domenicali
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Maurizio
M
Baldassarre
U.O. Infectious Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Michele
M
Bartoletti
Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.|Department of Pharmacology and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Marina
M
Naldi
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Maristella
M
Laggetta
Department of Pharmacology and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Carlo
C
Bertucci
U.O. Gastroenterology, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Antonio
A
Colecchia
U.O. Infectious Diseases, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.
Pierluigi
P
Viale
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Mauro
M
Bernardi
U.O. Semeiotica Medica, Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy.|Center for Applied Biomedical Research (C.R.B.A.), S.Orsola-Malpighi University Hospital, Bologna, Italy.
Paolo
P
Caraceni
D065290:Acute-On-Chronic Liver Failure / Q000401:mortality*; D000368:Aged; D000818:Animals; D001424:Bacterial Infections / Q000175:diagnosis*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000097:blood; D012372:ROC Curve; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin; D000075462:Serum Albumin, Human
D015415:Biomarkers; D020033:Protein Isoforms; D012709:Serum Albumin; C561522:ischemia-modified albumin; D002097:C-Reactive Protein; D000075462:Serum Albumin, Human
albumin non-oncotic properties; bacterial infection; cirrhosis; ischaemia-modified albumin