High Dose Albumin in Refractory Ascites

Summary

Advanced cirrhosis with complications is a serious problem imposing a heavy financial burden on health care system. Moreover, ascites is associated with increase in mortality rates among cirrhotic patients. Ascites pathogenesis is multifactorial including: portal hypertension; splanchnic and peripheral arterial vasodilation; and neurohumoral activation. Current management strategies include dietary sodium restriction and diuretic therapy, however, this strategy put patients at the risk of intravascular volume depletion, renal impairment, hepatic encephalopathy and hyponatremia. Moreover, around 10% of patients do not respond to this strategy (termed: diuretics resistant) with 50% of them die within 6 months. This sub-group is managed by frequent large volume paracentesis along with intravenous albumin administration and are usually considered for liver transplantation (LT) and TIPS. Nonetheless, Frequent paracentesis increases the risk of infection, bleeding, bowel perforation, paracentesis-induced circulatory dysfunction (PICD) and renal dysfunction in this sub-group of patients. The beneficial effect of human albumin might result from blood volume expansion tapering activated vasoconstrictor and sodium-retaining systems improving renal perfusion, hence regular infusion of albumin may be beneficial to prevent development of ascites and to improve survival. The positive effects of albumin are supported by previous studies; Romanelli et al, showed a significant increase in survival rate among cirrhotic patients with ascites when compared to those who did not receive albumin. Moreover, a randomized multicenter open label trial published in lancet last year, demonstrated that long term albumin administration improved 18-month survival, decreased the use of paracentesis and decrease in the incidence of cirrhosis related complications among cirrhotic patients with ascites. As of today, there's a limited use of regular high dose albumin in cirrhotic patients with ascites in US, despite being used elsewhere in the world as previously stated. The investigators wish to study long-term efficacy of human albumin administration in patients with decompensated cirrhosis to assess safety and efficacy, and prevention of complications of cirrhosis.

Timeline

Start

2019-03-25

Primary completion

2027-03-25

Completion

2027-06-25

Publications

• Results Di Pascoli M, Ceranto E, De Nardi P, Donato D, Gatta A, Angeli P, Pontisso P. Hospitalizations Due to Cirrhosis: Clinical Aspects in a Large Cohort of Italian Patients and Cost Analysis Report. Dig Dis. 2017;35(5):433-438. doi: 10.1159/000458722. Epub 2017 Mar 1.
• Results Gines P, Quintero E, Arroyo V, Teres J, Bruguera M, Rimola A, Caballeria J, Rodes J, Rozman C. Compensated cirrhosis: natural history and prognostic factors. Hepatology. 1987 Jan-Feb;7(1):122-8. doi: 10.1002/hep.1840070124.
• Results Schmidt ML, Barritt AS, Orman ES, Hayashi PH. Decreasing mortality among patients hospitalized with cirrhosis in the United States from 2002 through 2010. Gastroenterology. 2015 May;148(5):967-977.e2. doi: 10.1053/j.gastro.2015.01.032. Epub 2015 Jan 23.
• Results Pedersen JS, Bendtsen F, Moller S. Management of cirrhotic ascites. Ther Adv Chronic Dis. 2015 May;6(3):124-37. doi: 10.1177/2040622315580069.
• Results Moore KP, Aithal GP. Guidelines on the management of ascites in cirrhosis. Gut. 2006 Oct;55 Suppl 6(Suppl 6):vi1-12. doi: 10.1136/gut.2006.099580. No abstract available.
• Results Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther. 2005 Mar 1;21(5):525-9. doi: 10.1111/j.1365-2036.2005.02387.x.
• Results Romanelli RG, La Villa G, Barletta G, Vizzutti F, Lanini F, Arena U, Boddi V, Tarquini R, Pantaleo P, Gentilini P, Laffi G. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. World J Gastroenterol. 2006 Mar 7;12(9):1403-7. doi: 10.3748/wjg.v12.i9.1403.

Drugs

Indications

No indication recorded.