Mauro Bernardi Manuel Tufoni Carmen Serena Ricci Maria Elena Bonavita Giacomo Zaccherini Department of Medical and Surgical Sciences , University of Bologna , Italy Email : mauro . bernardi @ unibo . it

Hypoalbuminaemia is a typical feature of cirrhosis and represents an important and adverse prognostic factor . It results from both a decreased synthesis by liver cells and , to a lesser extent , to other factors such as plasma volume expansion diluting the extracellular fluid protein content , due to the renal retention of sodium and water , and an increased trans-capillary escape rate of albumin , which leads the protein to be lost towards the extravascular space .

Several studies have clearly established that albumin is effective in counteracting the hemodynamic dysfunction of advanced cirrhosis , which results from an arterial vasodilation mainly located in the splanchnic area , and represents the common background for several complications . These favourable effects are likely due not only to volume expansion , but also to the non-oncotic properties of albumin , such as antioxidant and scavenger activities , and its ability to preserve capillary integrity and permeability . ¹

Established indications to albumin administration in cirrhosis Prevention of renal failure in spontaneous bacterial peritonitis Spontaneous bacterial peritonitis ( SBP ) is

a frequent and life-threatening infection of ascitic fluid . The diagnosis is based on finding more than 250 polymorphonuclear cells / mmc in ascites , in the absence of an intra-abdominal source of infection or malignancy . Even without the occurrence of septic shock , SBP leads to a pro-inflammatory cytokine storm that further impairs cardiovascular dysfunction . The ensuing worsening in effective volaemia can lead to acute renal failure , with the phenotype of hepatorenal syndrome type 1 ( HRS-1 ) or acute tubular necrosis , which occurs in about 30 % of cases and represents a main cause of death . Indeed , SBP-related in-hospital mortality rates can be as high as 20 %, despite the resolution of infection . ² A prospective randomised study has shown the administration of a high dose of albumin ( 1.5 g / kg at diagnosis and 1 g / kg on day 3 ) in addition to antibiotic treatment decreases the incidence of renal failure ( from 30 % to 10 %) and improves in-hospital and 3-month survival . ³ The capacity of albumin to improve the outcome of patients with SBP has been confirmed in a recent metaanalysis of randomised trials . ⁴

The amount of albumin to be administered in this setting and whether all patients have to be treated have not been fully defined as yet . In fact , it would appear that only patients at high risk of developing renal failure ( baseline bilirubin > 4 mg / dl and / or creatinine > 1.0 mg / dl ) most benefit from albumin administration , suggesting that it could be restricted to high-risk patients . However , two large subsequent retrospective studies showed that the incidence of poor outcome in low-risk patients not treated with albumin is not negligible . It has also been reported that a reduced-dose regimen of albumin ( 1.0 g / kg on day 1 and 0.5 g / kg on day 3 ) is as effective as the standard regimen in preventing renal failure and reducing mortality . However , these results still need to be confirmed by further prospective studies in larger patient populations . Thus , to date , the European Association for the Study of the Liver recommends that all patients with SBP should receive intravenous albumin at the higher dosage in addition to antibiotics . ⁵

Diagnosis and treatment of hepatorenal syndrome HRS is a potentially reversible renal failure that occurs in patients with advanced cirrhosis , ascites and liver failure , associated with marked circulatory dysfunction . HRS is the clinical manifestation of a severe intra-renal vasoconstriction . This results from impaired effective volaemia secondary to both arterial vasodilation and cardiac dysfunction ( cirrhotic cardiomyopathy ), which lead to a striking compensatory activation of vasoconstrictor systems such as the

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