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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.


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