Clinical use of albumin in hepatology.

Abstract

Albumin has been the subject of much discussion and research for a long time. Hippocrates first mentioned some of its physiological properties, but albumin was not named or studied until the early 1800s. The modern use of human albumin was established during World War II due to the demand for plasma substitutes, while the first documented clinical use of human albumin occurred in 1941 in seven sailors severely burned during the attack at Pearl Harbour. The first report of administration of albumin to patients with cirrhosis was published by Janeway et al., who treated six patients with cirrhosis with 25 g albumin per day1. This protein was introduced as a treatment in the 1950s and was incorporated for many years in the management of patients with decompensated cirrhosis. There were, however, always varied opinions among hepatologists in relation to the use of albumin in liver cirrhosis. This review aims to highlight current thinking regarding albumin therapy in the setting of hepatology and also discusses its potential therapeutic applications based on the complex biochemistry of this multifunctional plasma protein. Properties and physiological functions of albumin Human serum albumin is an abundant multifunctional non-glycosylated, negatively charged plasma protein, which is synthesised primarily in the liver and is thought to be a negative acute-phase protein2. In healthy adults, albumin synthesis occurs predominantly in polysomes of hepatocytes (10–15 g/day) and accounts for 10% of total liver protein synthesis. Relatively small amounts of albumin are hepatologically stored (<2 g), the majority being released into the vascular space. Approximately 30%–40% of the albumin synthesised is retained within the plasma compartment. The remaining pool is located in tissues such as muscle and skin. Albumin is not stored hepatically and there is, therefore, no reserve for release on demand3. However, under physiological circumstances only 20–30% of hepatocytes produce albumin and synthesis can, therefore, be increased on demand by 200–300%. Synthesis is a constant process, regulated at both transcriptional and post-transcriptional levels by specific stimuli, but a change in interstitial colloid oncotic pressure is thought to be the predominant regulatory influence4. Albumin homeostasis is maintained by balanced catabolism occurring in all tissues, with most albumin (40%–60%) being degraded in muscles, the liver, and the kidneys. Studies of radiolabelled albumin catabolism in normal healthy young adult males indicate that the protein has a mean half-life of 14.8 days5. Colloid oncotic pressure Human serum albumin accounts for some 60% of the intravascular protein pool in healthy individuals, thereby being responsible for approximately 60% of plasma colloid oncotic pressure. Albumin is also responsible for water retention as the negative charges surrounding the protein molecules attract sodium ions. Its remaining contribution to colloid oncotic pressure is due to the Gibbs-Donnan effect of attracting other active positive ions, further enhancing its water-retaining effect6. In patients with hypoalbuminaemia (especially when it is associated with inflammation or sepsis) whose capillaries are known to be hyperpermeable, the leakage of albumin into the interstitial space draws water with it, producing oedema. Moreover, albumin may influence vascular integrity both directly, by binding in the interstitial matrix and subendothelium and reducing the permeability of these layers to large molecules, and indirectly, through its scavenging properties.