Determination of Effective Albumin in Patients With Decompensated Cirrhosis: Clinical and Prognostic Implications

Abstract

Background & Aims. Circulating albumin in cirrhosis can be dysfunctional due to accumulating structural damages, leading to the concept of effective albumin concentration (eAlb) referring to the albumin portion presenting structural and functional integrity. We aimed to estimate eAlb in patients with decompensated cirrhosis and analyze its relationships with albumin function and clinical outcomes as compared to total albumin concentration (tAlb). Approach & Results. We evaluated 319 cirrhotic patients hospitalized for acute decompensation (AD) with and without acute-on-chronic liver failure (ACLF) and 18 age-and sex-comparable outpatients with compensated cirrhosis. tAlb was quantified by standard assay, while eAlb was estimated combining liquid chromatography-electrospray ionization-mass spectrometry and standard methods. Albumin binding and detoxification efficiency were evaluated by electron paramagnetic resonance analysis. Circulating albumin in patients with decompensated cirrhosis displayed multiple structural abnormalities, with reversible oxidation and glycation being the most frequent. As a result, eAlb progressively declined with the worsening of cirrhosis, and was superior to tAlb in stratifying patients between compensated cirrhosis, AD and ACLF, as well as patients with and without complications. Moreover, eALB, but not tAlb, was closely associated with binding capacities in ACLF. Finally, eALB at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than tAlb. Conclusion: This large observational study provides the evidence in patients with decompensated cirrhosis that eAlb can be quantified and differentiated from tAlb routinely measured in clinical practice. As compared to tAlb, eAlb is more closely associated with disease severity and albumin dysfunction, and carries a greater prognostic power. These results prompt future research assessing eAlb as a novel biomarker for predicting prognosis and treatment response.

Hypoalbuminemia as Surrogate and Culprit of Infections

“…In patients with decompensated cirrhosis, serum albumin shows structural abnormalities, most often involving reversible oxidation and glycation [ 35 ], which lead to impaired binding capacity in albumin and increased risk of liver failure [ 36 ]. By combining liquid chromatography-electrospray ionization-mass spectrometry and standard methods of albumin determination, ‘effective’ albumin has been defined as the albumin isoform presenting structural and functional integrity as differentiated from ‘total’ albumin, which includes modified albumin.…”

“…By combining liquid chromatography-electrospray ionization-mass spectrometry and standard methods of albumin determination, ‘effective’ albumin has been defined as the albumin isoform presenting structural and functional integrity as differentiated from ‘total’ albumin, which includes modified albumin. Most importantly, it has been suggested that serum levels of ‘effective’ albumin may be a better prognostic indicator than ‘total’ albumin in patients with decompensated cirrhosis [ 36 ].…”

Nutrition in Patients with Type 2 Diabetes: Present Knowledge and Remaining Challenges

“…Protein restriction is not systematically advocated, as these patients usually tolerate a normal protein intake. Besides hypoalbuminemia, potentially requiring a higher protein intake, albumin glycation is present in T2D [ 193 ]. The structurally damaged albumin molecule is also dysfunctional, and albumin administration may be required to reduce ascites.…”

Albumin for cirrhosis‐related complications

“…There have been attempts to define an effective albumin concentration based on albumin functionality and concentration, but such definitions involve effective albumin quantification using techniques not commonly available in the clinical setting, and the results likely vary by specific clinical conditions 14 . However, results of such investigations provide important insights into the structural abnormalities of circulating albumin that occur in patients with decompensated cirrhosis, which lead to decreases in effective albumin concentrations with disease progression 15 . Additionally, these studies of effective albumin concentrations confirm the results of previous findings demonstrating that exogenously administered albumin cannot be assumed to have the same properties as endogenous albumin produced by the liver, since commercially available albumin preparations are known to undergo posttranslational modifications 16 …”