Human albumin in the management of complications of liver cirrhosis

  • Bernardi M, Maggioli C & Zaccherini G.
  • Critical Care, March 2012, 16:211.

This review paper examines the role of albumin in chronic liver disease, assessing the evidence for its use in several key clinical areas.

Human serum albumin makes up around 50% of serum protein, but as it does not easily cross capillaries it produces around 70% of plasma oncotic pressure; therefore, its role as one of the primary modulators of fluid distribution is apparent. It is exclusively synthesised in hepatocytes, with the level of production determined by the oncotic pressure in the extravascular space of the liver and influenced by hormones and cytokines. In terms of clinical use, the role of albumin as plasma expander tends to be reserved for certain circumstances – such as septic shock. Part of the reason for this restricted role is its relative cost, theoretical risk of viral transmission and availability of cheaper alternatives.

The role of albumin is not solely that of plasma expander; it binds to a number of molecules and is involved in delivering drugs, as well as acting to detoxify various substances – it is the primary antioxidant molecule available physiologically. A link has been identified between chronic disease and the proportion of oxidised albumin; in healthy individuals, only a small amount of oxidised albumin is present, yet this rises significantly in disease states, impairing its biological activity.

Liver cirrhosis leads to decreased serum albumin concentration in two known ways: it reduces synthesis from diseased hepatocytes, and increases the plasma fluid volume by retaining sodium and water. In the past it was believed that hypoalbuminaemia played a role in generating ascites, while it is now understood that they are both effects of cirrhosis.

Vasoactive substances are commonly produced in cirrhosis; nitrogen oxide, carbon monoxide and endocannabinoids – lowering vascular resistance. Cardiac output rises in order to compensate, leading to cirrhosis patients being functionally hypovolaemic despite elevated cardiac output. This puts even relatively stable patients at significant risk of cardiac insufficiency should fluid shifts occur. Albumin administration, coupled with other drugs, can play a key role in maintaining blood volume. Several randomised controlled trials (RCT) have demonstrated a benefit for preventing post-paracentesis circulatory dysfunction (PPCD), renal failure after spontaneous bacterial peritonitis (SBP) and in the treatment of hepatorenal syndrome (HRS).

Paracentesis remains a cornerstone of treatment for patients with excessive ascites, with simultaneous administration of albumin therapy causing a significant reduction in the incidence of PPCD. The review notes a recent meta-analysis which demonstrated that albumin reduced the incidence of PPCD, hyponatraemia and mortality.

Hepatorenal syndrome is the development of renal disease without a clear cause in a patient with pre-existing cirrhosis. It has a very poor prognosis, 90% 2-week mortality if untreated. Trials have demonstrated that albumin and terlipressin have a synergistic effect – expanding plasma volume and acting as a vasoconstrictor, this improves renal blood flow, thus improving renal function. Although the numbers studied to date have been small, they have shown a consistent benefit.

SBP may precipitate circulatory dysfunction and resultant HRS; it too has a high mortality rate. Treatment with albumin was noted in one RCT to decrease mortality from 29% to 10% versus cefotaxime alone. It is unclear at publication whether other colloids may have been equally effective.

The use of albumin in chronic ascites is much less clear than the previous examples; some studies have suggested a delay in fluid reaccumulation, but no mortality benefit has ever been demonstrated.

Detoxification systems have been explored in an effort to mimic the non-oncotic properties of albumin in cirrhosis – however these are at an early stage, and at the time of publication have yet to demonstrate any benefit.

Explore the Fluid Management Knowledge Centre to discover more about the role of fluid therapy in cardiac surgery, critically ill patients, liver cirrhosis, and more.

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