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High doses of albumin reduced systemic inflammation and cardiocirculatory dysfunction in patients with decompensated cirrhosis, according to a European analysis. The new findings suggest that the protein has beneficial effects beyond plasma volume expansion, said Javier Fernández, MD, PhD, of the University of Barcelona in Spain, and co-authors.

Data from their Pilot-PRECIOSA study, published in , indicated that both short- and long-term high-dose albumin – but not low-dose albumin – was associated with normalized serum albumin levels and improved circulatory stability and left ventricular function. Interestingly, high-dose therapy also prevented the newly observed phenomenon of sudden transient bursts of circulatory dysfunction and did so without inducing albumin overdose.

Albumin also significantly correlated with reduced plasma levels of the inflammatory cytokines interleukin 6, interleukin 1 receptor antagonist, granulocyte colony-stimulating factor, and vascular endothelial growth factor -- with no significant changes in portal pressure. Similar immunomodulatory effects emerged in the INFECIR-2 trial, which also saw significant reductions in plasma cytokines with albumin therapy.

Albumin's immune-modulating effect could stem from its scavenging function and ability to bind and its inactivate inflammatory promoters such as pathogen-associated molecular patterns (for example, bioactive lipid metabolites), prostaglandins, reactive oxygen species, and nitric oxide, the researchers said. "However, this explanation may be too simplistic, and further [investigations] are clearly needed to understand the anti-inflammatory effect of albumin treatment in cirrhosis."

Several previously unreported observations on the pathophysiology of decompensated cirrhosis and the albumin effect emerged:

• The long-term albumin dosage required to normalize serum albumin concentration is much higher than that used in randomized controlled therapeutic trials to date such as the

• Circulatory dysfunction is not a steady state or a slowly progressive process, as traditionally thought, but is an extremely unstable condition

• Similarly, systemic inflammation in cirrhosis is also unstable, characterized by acute bursts of circulating cytokines in the absence of any identifiable precipitating event

• High-dose albumin is associated with significant improvement in left ventricular cardiac function, an important mechanism of systemic circulatory dysfunction

• Plasma levels of interleukin showed that long-term high-dose albumin treatment has immunomodulatory effects in decompensated cirrhosis

The authors noted that in cirrhosis is currently based on empirical assumptions and the concept that albumin mainly acts as a plasma volume expander.

"The study demonstrates that to improve circulatory function and attenuate inflammatory response, patients with cirrhosis and ascites must receive high doses of albumin capable of normalizing albumin concentration," Fernández told MedPage Today. "In that sense, physicians should focus their attention on normalizing levels of this key molecule."

The is a proof-of-concept, open-label, multicenter, non-randomized, prospective, phase IV, safety, and dosage-exploratory investigation. Conducted from 2009 to 2014, it sought information for designing the current multicenter randomized controlled therapeutic trial launched in 2018 to assess 1-year albumin treatment in the prevention of acute-on-chronic liver failure (ACLF) and mortality.

The study included 18 patients with decompensated cirrhosis and no bacterial infection. The sample, mean age of 56, included 13 males and 12 patients with alcoholic cirrhosis.

The pilot study evaluated long-term (i.e., 12-week) treatment with low-dose albumin (1 g/kg body weight every 2 weeks), and high-dose albumin (1.5 g/kg every week), on serum albumin, plasma renin, cardiocirculatory function, portal pressure, and plasma levels of cytokines.

Among the specific findings were the following:

• High-dose albumin was associated with an average fall in baseline plasma IL-6 concentration of 56%, from 123.5 pg/mL to 62.5 pg/mL (P=0.76)

• Plasma renin activity fell from 5.5 ng/mL.h at baseline to 4.9 ng/mL.h (P=0.17), for a change of 2%

• Average serum albumin level increased with high-dose treatment from 27.6 g/L to 39.2 g/L, for a change of 48.7% (P=0.004)

• Low-dose treatment did not have the same impact, showing changes in these three measures of –7.6%, –6.7%, and 20.2%, respectively

The researchers also assessed the effect of short-term (1-week) treatment with antibiotics alone or antibiotics plus albumin using biobanked data on 78 of the original 118 patients in the . Results from that phase IV, randomized, open-label, parallel, multicenter trial conducted from 2014 to December 2016 to assess short-term albumin treatment in the prevention of ACLF and hospital mortality with decompensated cirrhosis and acute bacterial infections are expected to be published soon in Gastroenterology, Fernández and co-authors said.

A limitation of Pilot-PRECIOSA, they added, was the low number of patients included.

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