Human albumin : liver disease |
|||
|
established treatment of ascites requires moderated dietary sodium restriction and diuretics . LVP are needed for tense ascites or once refractory ascites has developed . 5 As the renal sodium and water retention leading to ascites formation in concert with portal hypertension results from the reduction of the effective blood volume , it sounds rational trying to expand plasma volume by albumin administration . Studies performed in small patient populations in the 1960s failed to demonstrate a clear advantage . More recently , a prospective clinical trial randomised 126 hospitalised patients with ascites to receive diuretics associated or not with low doses of albumin ( 12.5 g / day ). Then , they were followed as outpatients receiving 25g / week of albumin , for a median follow-up of 20 months . 14 Albumin improved the response rate to diuretics and reduced the recurrence rate of ascites , but had no effect on survival . Further data analysis showed that the beneficial effects of albumin were only seen in patients receiving an intermediate dose of diuretics ( K-canrenoate 200mg / day plus furosemide 25mg / day ), and the cost / benefit ratio was only favourable to albumin in the first in-hospital part of the study .
A subsequent trial performed by the same research group in 100 consecutive cirrhotic patients admitted for first-onset ascites and followed for a median time of 84 months , reported that long-term albumin administration ( 25g / week for the first year , then 25g every two weeks ) was able to reduce ascites recurrence and increase patient survival with respect to standard medical treatment . 15 Unfortunately , no other controlled clinical trials aimed at evaluating the effectiveness of prolonged albumin administration in the treatment of ascites have been performed so far . Due to its high cost and inconclusive evidence supporting its prolonged administration , the use of albumin for the treatment of ascites is still controversial and no recommendation has been made at this regard by current guidelines .
To clarify the role of the log-term administration of albumin for the treatment of ascites , a multicentre randomised clinical trial ( NCT 01288794 , www . clinicaltrials . gov , the “ A . N . S . W . E . R . Study ”) is currently ongoing in Italy . This study will enrol approximately 400 patients , thus having the sample size sufficient to assess whether the long-term albumin administration ( 40g / week for 18
|
months ) can reduce the incidence of refractory ascites and other complications , such as HRS and bacterial infections , and improve survival at sustainable costs .
Hypervolemic hyponatraemia Hypervolemic hyponatraemia ( serum sodium < 135 mmol / l ) is frequently seen in patients with cirrhosis and ascites and is associated with a poor outcome . 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 . Nevertheless , because of the lack of controlled clinical trials , albumin administration in this setting is not recommended by current guidelines . 5
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 . Thanks to its anti-oxidant and anti-inflammatory properties , albumin might be useful to counteract these mechanisms . 1 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 . A subsequent randomised clinical trial in patients with severe HE showed the favourable effect of albumin dialysis in addition to standard medical treatment . Despite the fact that 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 . l
References
1 . Garcia-Martinez R et al . Albumin : Pathophysiologic basis of its role in the treatment of cirrhosis and its complications . Hepatology 2013 ; ( Epub ahead of print ).
2 . Wong F et al . International Ascites Club . Sepsis in cirrhosis : report on the 7th meeting of the International Ascites Club . Gut 2005 ; 54:718 – 25 .
3 . Sort P et al . Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis . N Engl J Med 1999 ; 341:403 – 9 .
4 . Salerno F , Navickis RJ , Wilkes MM . Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis : a meta-analysis of randomized trials . Clin Gastroenterol Hepatol 2013 ; 11:123 – 30 .
5 . European Association for the Study of the Liver . EASL clinical practice guidelines on the management of ascites , spontaneous bacterial peritonitis , and hepatorenal syndrome in cirrhosis . J Hepatol 2010 ; 53 : 397 – 417 .
6 . Arroyo V , Terra C , Ginès P . Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome . J Hepatol 2007 ; 46:935 – 46 .
7 . Salerno F et al . Diagnosis , prevention and treatment of hepatorenal syndrome in cirrhosis . Gut 2007 ; 56:1310 – 8 .
8 . Ortega R et al . Terlipressin therapy with and without albumin for patients with hepatorenal syndrome : results of a prospective , nonrandomized study . Hepatology 2002 ; 36:941 – 8 .
9 . Fernández J et al . A randomized unblinded pilot study comparing albumin versus hydroxyethyl starch in spontaneous bacterial peritonitis . Hepatology 2005 ; 42:627 – 34 .
10 . Bortoluzzi A et al . Positive cardiac inotropic effect of albumin infusion in rodents with cirrhosis and ascites : molecular mechanisms . Hepatology 2013 ; 57:266 – 76 .
11 . Runyon BA . Management of adult patients with ascites due to cirrhosis : an update . Hepatology 2009 ; 49:2087 – 107 .
12 . Bernardi M , Caraceni P , Navickis RJ , Wilkes MM . Albumin infusion in patients undergoing large-volume paracentesis : a meta-analysis of randomized trials . Hepatology 2012 ; 55:1172 – 81 .
13 . Guevara M et al . Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis . A randomized , controlled study . J Hepatol 2012 ; 57:759 – 65 .
14 . Gentilini P et al . Albumin improves the response to diuretics in patients with cirrhosis and ascites : results of a randomized , controlled trial . J Hepatol 1999 ; 30:639 – 45 .
15 . Romanelli RG et al . Long-term albumin infusion improves survival in patients with cirrhosis and ascites : an unblinded randomized trial . World J Gastroenterol 2006 ; 12:1403 – 7 .
|
13 |
www . hospitalpharmacyeurope . com |