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Human albumin: liver disease

renin-angiotensin system, sympathetic nervous system, and arginine vasopressin.6 There are two types of HRS7


- Type-1, which is characterised by a rapid and progressive impairment of renal function defined by doubling of the initial creatinine concentrations to a level greater than 1.5 mg/dl in less than two weeks. It often appears after a precipitating event, particularly SBP or other infections, and has a very poor prognosis, with a median survival less than two weeks. - Type-2 HRS, which is characterised by moderate renal failure (serum creatinine from 1.5 to 2.5 mg/dl), with a steady or slowly progressive course. It often appears spontaneously and is typically associated with refractory ascites. Type-2 HRS also has a poor prognosis, with a median survival of about six months. The diagnosis of HRS requires the exclusion of other forms of renal failure and, in particular, of hypovolaemia. For this reason, diagnosis is made in patients who fail to improve serum creatinine to a level ≤ 1.5 mg/dl after at least 2 days of diuretic withdrawal and volume expansion. The latter is preferentially performed with albumin administration (recommended dose: 1g/kg of body weight per day, up to a maximum of 100g/day) rather than saline solution, in order to achieve a greater and more sustained expansion and avoid sodium load.5,7 Once diagnosis is established, the most effective treatment of HRS includes the administration of vasoconstrictors (mostly terlipressin) in association with intravenous albumin (1g/kg at diagnosis, followed by 40g/day up to 2 weeks).5

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treatment improves renal function in about 40% of cases and leads to the resolution of HRS in about one-third of cases. Survival is only improved in the short term, but this result should not be surprising, as patients with HRS usually have a very advanced cirrhosis. Interestingly, the association of terlipressin plus albumin is more effective than terlipressin alone.8 These favourable effects are amenable to an improvement of effective volaemia, which not only results from plasma volume expansion, but is also due to improvements in stroke work and peripheral vascular resistance, as shown by comparing the effect of albumin and hydroxyethyl starch. These results suggest an effect of albumin on endothelial function, as plasma Von Willebrand-related antigen only decreased in patients treated with albumin and serum

Table 1: Indications to albumin administration in patients with liver cirrhosis Complications of cirrhosis

Albumin use SBP HRS PPCD Non SBP infections Ascites Hyponatemia Hepatic encephalopathy

1.5g/kg on day 1 and 1g/kg on day 3 (in association with anibiotics)

1g/kg on day 1 and 40g/day from day 2 to resolution (in association with terlipressin)

8g/l of ascites removed (above 51)

1.5g/kg on day 1 and 1g/kg on day 3 (not yet enough evidence, further studies required)

Not yet enough evidence for the utility of chronic use (ANSWER Study currently undergoing)

Volume expansion with albumin has been proposed (lack of randomised controlled trials)

Detoxification properties may have a role in HE therapy SBP, spontaneous bacterial peritonitis; HRS, hepatorenal syndrome; PPCD, post-paracentesis circulatory dysfunction

nitrates and nitrites only increased in patients treated with hydroxyethyl starch.9 Furthermore, in an experimental model of cirrhosis, albumin infusion was also able to restore an impaired cardiac contractility.10

Prevention of post-paracentesis circulatory dysfunction

Large volume paracentesis (LVP) is the current treatment of choice for patients with tense and refractory ascites.5


removal of large volumes of ascitic fluid can be followed by post-paracentesis circulatory dysfunction (PPCD), defined as a significant increase (>50%) in plasma renin activity six days after LVP. PPCD is a circulatory dysfunction characterised by an exacerbation of arteriolar vasodilation, reduction of effective blood volume, rapid re-accumulation of ascites, increased risk of HRS, water retention with dilution hyponatraemia and shortened survival. In several randomised trials, albumin was able to lower the incidence rate of PPCD and showed its superiority when compared with other plasma expanders. On the basis of such evidences, both American and European guidelines recommend the administration of 8g of albumin/L of tapped ascites, when more than 5 litres of ascites are removed.5,11 Due to high cost and potential low availability of albumin, many alternatives have been tested, also including vasoconstrictors. However, in support of current recommendations, a recent meta-analysis of randomised trials has confirmed that albumin not only reduces the occurrence of PPCD more efficiently than any other plasma expander or vasoconstrictor, but is also able to lower the incidence of hyponatraemia and improve survival.12

Controversial indications of albumin in cirrhosis Bacterial infections other than SBP Bacterial infections are very common complications of liver cirrhosis and represent a major cause of hospitalisation and death in patients with advanced disease. As reported above, it has long been recognised that renal failure develops in about one-third of patients with SBP. It has become clear that even non SBP-related infections can be followed by renal failure (about 25% of cases), which is also a major predictor of mortality in this setting.2 Data on the effect of albumin administration to patients with non SBP-related infections are few. A recent randomised study showed that the administration of albumin (1.5 g/kg at diagnosis and 1 g/kg at day 3) in association with antibiotics was able to improve circulatory and renal functions with respect to the administration of antibiotics alone. However, no significant effects on the incidence of renal failure were seen and the cumulative 3-month survival did not differ between the two groups, even though an advantage in the albumin group was found after adjusting according to variables with independent predictive value.13

Thus, further studies

are needed to clarify the role of albumin administration in this setting, mainly aimed at identifying those patients who are most at risk of developing infection- induced complications and mortality.

Prolonged use of albumin for the treatment of ascites

Ascites is a common complication of liver cirrhosis and its occurrence is associated with a worsening of prognosis. The

Controversial or experimental use

According to guidelines

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