Impaired albumin function: a novel potential indicator for liver function damage?

Abstract

Albumin is the most abundant plasma protein and albumin infusion is commonly used. Conventionally, the biologic and therapeutic effects of albumin have been thought to be due to its oncotic properties. However, albumin has a variety of biologic functions, including molecular transport, anti-oxidation, anti-inflammation, endothelial stabilisation, anti-thrombotic effects, and the adjustment of capillary permeability. Despite this, the functions of albumin have not been thoroughly investigated. Recent studies have shown non-alcoholic fatty liver disease (NAFLD), viral hepatitis, cirrhosis, and liver failure to be associated with impairments in albumin function, which are associated with impairments in liver function and disease prognosis. Post-translational modifications of albumin cause structural modifications that affect protein function. Recently, the concentration of albumin associated with normal function, the 'efficient albumin concentration', has been attracting more interest. In addition, although many biologic markers, including albumin concentration, are widely used for the assessment of early liver dysfunction in patients with liver diseases, the predictive values are unsatisfactory. However, clinical evidence has suggested that albumin function may represent a novel biomarker of early impairment in liver function. In this review, we summarise the factors affecting albumin function and discuss the clinical significance of impairments in albumin function in various liver diseases.Key messagesThe importance of albumin depends not only on its concentration, but also on its various physiological functions.Impaired albumin function has been reported in a variety of liver diseases, and is associated with disease severity and prognosis, thereby proposing the concept of 'effective albumin concentration'.Albumin dysfunction occurs earlier than other conventional indicators, and albumin dysfunction may be a new biomarker of early impairment in liver function.Many exogenous and endogenous factors lead to post-translational modifications of albumin, which alters the three-dimensional structure of albumin, resulting in a decrease in its biological activity.

Keywords: Human serum albumin; albumin function; biomarker; liver function; non-oncotic function.

Figure 1.

The three-dimensional structure of human serum albumin. HSA consists of three homologous domains (I-III), each of which contains two subdomains (A and B). Binding site I and binding site II, and Cys34 are indicated by arrows.

Figure 2.

The alterations of albumin function in liver diseases. Many factors including hepatitis virus, alcohol intake, metabolic disorders, surgical trauma and oxidative stress result in the PTMs of albumin. The impaired three-dimensional structure will cause decreased albumin function in maintaining plasma oncotic pressure, dissolving, binding and transporting endogenous and exogenous molecules, antioxidant, anti-inflammatory, haemostatic effects, endothelial stabilisation and adjusting capillary permeability, which has an impact on a variety of liver diseases. PTM, Post-translational modifications