Targeted Albumin Infusions Do Not Improve Systemic Inflammation or Cardiovascular Function in Decompensated Cirrhosis

Abstract

INTRODUCTION:Albumin is recommended in decompensated cirrhosis, and studies have shown potential immunomodulatory effects. However, 2 large trials of repeated albumin infusions demonstrated contrasting results between outpatients and hospitalized patients. We investigated markers of systemic inflammation, immune function, albumin binding, and cardiovascular function using samples from Albumin To prevenT Infection in chronic liveR failurE (ATTIRE) taken at baseline, day 5, and day 10 of the trial to identify why targeted albumin infusions had no effect in hospitalized patients.METHODS:Plasma samples were analyzed from 143 patients (n = 71 targeted albumin; n = 72 standard care at baseline) for cytokines, cardiovascular markers, prostaglandin E2, the effect of plasma on macrophage function, and albumin radioligand binding and oxidation status. The sample size was based on our feasibility study, and samples were selected by a trial statistician stratified by the serum albumin level and the presence of infection at randomization and analyses performed blinded to the study arm. Data were linked to 3-month mortality and treatment groups compared.RESULTS:Increased baseline model for end-stage liver disease score, white cell count, calprotectin, CD163, tumor necrosis factor, renin, atrial natriuretic peptide, and syndecan-1 were associated with 3-month mortality. Despite infusing substantially differing volumes of albumin, there were no significant differences in inflammatory markers, albumin–prostaglandin E2 binding, or cardiovascular markers between treatment arms.DISCUSSION:Contrary to many preclinical studies, targeted intravenous albumin therapy in hospitalized decompensated cirrhosis had no effect across a broad range of systemic inflammation, albumin function, and cardiovascular mediators and biomarkers compared with standard care, consistent with the null clinical findings.

Use of non-selective B-blockers is safe in hospitalised decompensated cirrhosis patients and exerts a potential anti-inflammatory effect: data from the ATTIRE trial

“…Data were taken from our published dataset in which 142 patients' samples (n = 71 in targeted HAS arm, n = 71 in standard of care arm) were blindly analysed. 23 All patients selected were enrolled in the trial for at least 5 days. For this paper we divided patients into those taking NSBBs (n = 23) or not (n = 119) at baseline but did not subdivide into treatment groups as samples were taken at study recruitment prior to albumin treatment.…”

“…We did not examine the plasma inflammatory markers after baseline in view of the potential confounding effect of targeted albumin therapy, 24 although we previously found no effect of albumin on these overall. 23 LBP, sCD14, TNF, IL-6, IL-8 and PCT evaluation was undertaken via Luminex assay (R&D Systems, Minneapolis, MN) according to the manufacturer's instructionssee Supplementary material and Supplementary Table 1 for details.…”

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

“…On the other hand, however, there are studies that suggest that the effect of albumin may not be so strong. A recent clinical study revealed that targeted albumin infusion did not attenuate systemic inflammation or improve cardiac function in patients with decompensated cirrhosis (139). Another trial suggested that infusing albumin to normal levels in patients with advanced liver disease may not provide additional benefit (13).…”

Plasticity of monocytes and macrophages in cirrhosis of the liver

“…An in vitro study revealed that the augmentation of serum albumin above 30 g/L was associated with the reversibility of plasma-mediated immune dysfunction by binding and inactivation PGE 2 (China et al, 2018). Intravenous albumin had however no effect on systemic inflammation, albumin function, cardiovascular mediators and biomarkers compared with standard of care in hospitalized decompensated cirrhosis (China et al, 2022). To date, the standard of care remains the treatment with albumin in addition to appropriate antibiotics in SBP (Bajaj et al, 2021) as well as in acute kidney injury.…”