TABLE 1
Indications to albumin administration in patients with liver cirrhosis
Clinical setting
SBP
HRS
Albumin use
1.5g / kg on day 1 and 1g / kg on day 3 ( in association with antibiotics )
Diagnosis : 1g / kg for two consecutive days Treatment : 20 – 40g / day in association with terlipressin or noradrenaline
PICD 8g / l of ascites removed ( above 5l )
Non-SBP infections
Hyponatraemia
Hepatic encephalopathy
Decompensated cirrhosis
1.5g / kg on day 1 and 1g / kg on day 3 ( not yet enough evidence , further studies required )
Volume expansion with albumin has been proposed ( lack of randomised controlled trials )
Detoxification properties may have a role in therapy
40g twice a week for 2 weeks , 40g / week thereafter ( dose and schedule of albumin administration to be further refined )
SBP , spontaneous bacterial peritonitis ; HRS , hepatorenal syndrome ; PICD , paracentesis-induced circulatory dysfunction
recommend the administration of 8g albumin / l of tapped ascites , when more than 5l of ascites are removed . 11 , 18 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 metaanalysis of randomised trials has confirmed that albumin not only reduces the occurrence of PICD more efficiently than any other plasma expander or vasoconstrictor but is also able to lower the incidence of hyponatraemia and improve survival . 19
Controversial indications for 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 onethird 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 . 7
Data on the effect of albumin administration to patients with non SBP-related infections are few . A randomised study showed that the administration of albumin ( 1.5g / kg at diagnosis and 1g / 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 three-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 . 20 Similar results were reported by a subsequent large randomised trial , as albumin infusion delayed the onset of renal failure but did not improve renal function or survival at three months . 21 Moreover , pulmonary oedema developed in 8 / 96 ( 8.3 %) patients in the albumin group . 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 .
Hypervolaemic hyponatraemia Hypervolaemic hyponatraemia ( serum sodium < 135mmol / l ) is frequently seen in patients with cirrhosis and ascites and is associated with a poor outcome . 22 Although hyponatraemia can occur spontaneously , it is often induced by diuretic administration , LVP without albumin infusion , bacterial infections and renal failure . Such a complication results from effective hypovolaemia secondary to splanchnic arterial vasodilatation , which , in turn , impairs renal free water generation and evokes the non-osmotic secretion of vasopressin . Thus , beside diuretic withdrawal and water restriction , volume expansion with albumin has been proposed and many physicians commonly prescribe albumin in cirrhotic patients with hyponatraemia . 22 Nevertheless , because of the lack of controlled clinical trials , albumin administration in this setting is not recommended by current guidelines . 11
Hepatic encephalopathy Hepatic encephalopathy ( HE ) is a neuropsychiatric syndrome complicating acute and chronic liver failure . HE is classically attributed to the accumulation of several substances ( mostly ammonia ) produced in the gut and normally metabolised by the liver . However , in recent years , an important pathophysiological role of other factors , such as inflammation , bacterial translocation and oxidative stress , has been demonstrated . 23 Thanks to its anti-oxidant and anti-inflammatory properties , albumin might be useful to counteract these mechanisms . A clinical study compared the effect of volume expansion with 4.5 % albumin or colloid in patients with diuretic-induced HE , showing a reduction in plasma ammonia levels in both groups , possibly due to an increase in urinary excretion . However , an improvement in mental state was only observed in those patients treated with albumin , in whom there was a concomitant reduction in oxidative stress . 24 A subsequent randomised clinical showed that the combination of lactulose plus albumin was more effective than lactulose alone in the treatment of overt HE . 25 Interestingly , a greater reduction in plasma levels of arterial ammonia , pro-inflammatory cytokines and endotoxins occurred in patients who received albumin . Even though HE remains an unclear indication to albumin administration , these data suggest that the detoxification properties of albumin may have a role in the treatment of this condition .
New perspective : long-term albumin administration in decompensated cirrhosis The efficacy of long-term albumin administration to patients with cirrhosis and ascites has long be debated . However , the investigations devoted to this matter are relatively few . In 1999 , a prospective clinical trial randomised 126 hospitalised patients with ascites to receive diuretics associated or not with low doses of albumin ( 12.5g / day ). Then , they were followed as outpatients receiving 25g / week of albumin , for a median follow-up of 20 months . 26 Albumin improved the response rate to diuretics and reduced the recurrence rate of ascites but had no effect on survival . Further data analysis showed
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