​​​​ATTIRE Randomised Clinical Trial

Figure taken from Choe et al Hepatology 2015. 

Albumin could thus be repurposed as an effective immune restorative drug in patients with decompensated liver cirrhosis. We aim to evaluate treatment with 20% HAS to see if raising and maintaining serum albumin levels at near normal will result in fewer nosocomial infections in these patients and less sepsis-related organ failure, reduced length of stay and lower mortality. 

Scientific Theory behind ATTIRE

Liver disease is a major challenge facing the NHS with bacterial infection the most serious cause of morbidity and mortality in patients with advanced liver disease.

A defective innate immune response was first observed in cirrhosis 30 years ago and is considered to underlie the predisposition to, and poor outcome from, infection. There is however no medical strategy to restore immune competence in these patients.

Elevated circulating Prostaglandin E2 (PGE2) levels have been shown to contribute to immune suppression in liver cirrhosis. PGE2 is more bioavailable and, consequently, more immune suppressive because of decreased serum albumin levels, as albumin binds and catalyses inactivation of PGE2. Albumin is synthesised exclusively in the liver and levels fall as the synthetic function of the liver declines with worsening cirrhosis. The functional binding capacity of albumin is also known to be dysfunctional in liver cirrhosis. 

Useful references

China L et al. Administration of Albumin Solution Increases Serum Levels of Albumin in Patients With Chronic Liver Failure in a Single-Arm Feasibility Trial. Clin Gastroenterol Hepatol. 2018 May;16(5):748-755.e6. 

China L et al. Albumin Counteracts Immune-Suppressive Effects of Lipid Mediators in Patients With Advanced Liver Disease. Clin Gastroenterol Hepatol. 2018 May;16(5):738-747

O'Brien, A.J., et al. Immunosuppression in acutely decompensated cirrhosis is mediated by prostaglandin E2. Nature medicine 20, 518-523 (2014).

Choe, W. and S. Baik, Prostaglandin E2 -mediated immunosuppression and the role of albumin as its modulator. Hepatology, 2015. 61(3): p. 1080-2

Patel, A., Laffan, M.A., Waheed, U. & Brett, S.J. Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality. Bmj 349, g4561 (2014).

Fernandez, J., et al. Effect of intravenous albumin on systemic and hepatic hemodynamics and vasoactive neurohormonal systems in patients with cirrhosis and spontaneous bacterial peritonitis. Journal of hepatology 41, 384-390 (2004).

Sort P, N.M., Arroyo V, Aldeguer X, Planas R, Ruiz-del-Arbol L, Castells L, Vargas V, Soriano G, Guevara M, Ginès P, Rodés J. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 341, 403-409 (1999).

Thevenot, T., et al. Effect of albumin in cirrhotic patients with infection other than spontaneous bacterial peritonitis. A randomized trial. Journal of hepatology 62, 822-830 (2015).

Guevara, M., et al. Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study. Journal of hepatology 57, 759-765 (2012).

Caironi, P., et al. Albumin replacement in patients with severe sepsis or septic shock. The New England journal of medicine 370, 1412-1421 (2014).