Human albumin in the management of complications of cirrhosis.

Human serum albumin is the most abundant plasma protein, representing about 50% of the total protein content (3.5-5 g/L). Albumin is a protein of 585 amino acids and 66 kDa of molecular weight encoded by a gene on chromosome 4 and is exclusively synthesized by liver cells, which release it directly into the blood stream without storage. Under physiological conditions, only 20-30% of hepatocytes are committed to the production of 9-12 grams of albumin per day; therefore, the liver has a large functional reserve, so that it can increase the synthesis of this protein by 3-4 times, if necessary. The production of albumin is mainly regulated by osmolarity and oncotic pressure of interstitial fluid in the liver extravascular space, but it is also induced by hormonal factors (insulin, cortisol and growth hormone) and inhibited by acute phase cytokines, such as IL-6 and TNF-alpha. As serum albumin hardly crosses the majority of capillaries, it remains in the blood stream and generates about 70% of the plasma oncotic pressure. This feature is due 2/3 to a direct osmotic effect and 1/3 to the Gibbs-Donnan effect, which derives from its strong negative charges attracting positively charged molecules in the intravascular compartment. As a result, albumin is a main modulator of fluid distribution throughout body compartments. Its capacity of expanding the plasma volume represents the pathophysiological background for the use of human albumin in many clinical conditions; nevertheless, its administration is often inappropriate. This is largely due to a common belief in its efficacy, whereas many indications are still under debate or have been disproved by evidence-based medicine. Indeed, the high cost, the theoretical risk of viral disease transmission, and the availability of cheaper alternatives should be carefully weighed in albumin prescription. At present, it is generally accepted that the administration of non-protein colloids and crystalloids represents the first-line treatment of resuscitation, while the use of albumin in critically ill patients should be reserved to specific conditions, such as in patients with septic shock. Albumin administration is not recommended to correct hypoalbuminaemia per se (i.e. not associated with hypovolaemia) or for nutritional intervention, but these indications are often disregarded in clinical practice. Albumin is also prescribed in certain specific conditions and diseases, such as kernicterus, plasmapheresis, and graft versus host disease, even though these indications are not supported by definite evidence. Although the clinical use of albumin is mainly related to plasma volume expansion, albumin is more than a volume expander being provided of further biological properties: it binds and transports a variety of water-insoluble molecules, metals, and drugs, with implications for delivery and efficacy of drugs, including antibiotics, and for detoxification of endogenous and exogenous substances. Furthermore, it constitutes the main circulating antioxidant in the body, being the major extracellular source of reduced sulfhydryl groups, potent scavengers of reactive oxygen species.