COMMENTARY

Infusion of Evidence: The Albumin Effect in Cirrhosis Becomes Clearer

David A. Johnson, MD

Disclosures

July 10, 2019

Patients with cirrhosis have a significant reduction in cardiovascular and cardiopulmonary function. Arteriolar dilation, particularly in the splanchnic circulation, leads to a lessened arterial volume with a subsequent reduction in cardiac output. This "hypovolemia" can lead to resultant activation of compensatory neurohumoral pathways, which can affect renal perfusion and function. These cardiovascular compromises are integral in the decompensation of ascites and renal failure seen in patients with advanced cirrhosis.

A recently published two-part study[1] provides yet more evidence that using albumin infusions to target normal serum levels can have a significantly positive role in combating these effects in patients with decompensated cirrhosis, with and without bacterial infections. Although the ultimate goal of these dual studies is to assess the value of short- and long-term albumin at preventing acute liver failure or mortality in this population, the results offered in this report provide crucial new insights into just how IV albumin may impart these benefits.

In the first part of this study, researchers conducted a pilot proof-of-concept analysis involving 18 patients without bacterial infection who were randomly assigned to receive high-dose (1.5 g/kg infusion weekly) or low-dose albumin (1 g/kg every 2 weeks) albumin over 12 weeks. They observed that high-dose but not low-dose albumin was associated with significant improvements in circulatory and left ventricular function, as measured in the outcomes of pulmonary capillary wedge pressure, cardiac index, left ventricular stroke, and systolic volumes. Of note, these beneficial effects were not associated with a worsening of cardiac preload or portal hypertension (assessed by hepatic venous pressure).

In the second part of the study, researchers randomly assigned 118 patients hospitalized with decompensated cirrhosis and acute bacterial infections, unrelated to spontaneous bacterial peritonitis, to receive antibiotics alone or in combination with two separate doses of albumin (1.5 g/kg on day 1 and 1.0 g/kg on day 3). As in the first part of this study, researchers observed beneficial effects of albumin infusion on markers/regulators of systemic inflammation, specifically cytokines, chemokines, growth factors, and endothelial dysfunction.

Why Albumin Might Work in Cirrhosis

Although there are a number of reports on the benefits of IV albumin, few have investigated the pathophysiologic explanation for why it occurs. This new study fills that void by adding compelling and substantive information on the potential reasons that IV albumin has beneficial effects on cardiocirculatory dysfunction, systemic inflammation, and immune function. Increased systemic inflammation has a major role in hepatic decompensation.[2] The ability of albumin to bind to proinflammatory molecules makes intrinsic sense in understanding its value in mitigating risk in the decompensated cirrhosis-associated inflammatory and circulatory organ dysfunction. It is important to note that this new analysis found that high- but not low-dose albumin was associated with these favorable improvements in immunologic effect.

This study did not include assessments to measure whether patients experienced improved function. Future studies will hopefully explore whether such outcomes accompany these physiologic improvements, to better understand the clinical value of albumin in this population.

Although we await more data from ongoing studies in this area, in my view, these findings, coupled with the ANSWER trial demonstrating an amazing reduction in mortality,[3] strongly support considering programmatic administration of IV albumin in patients with uncomplicated decompensated cirrhosis as a potential new standard of care.

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