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.

Figure 1.

Baseline markers of circulatory and renal function in survivors vs nonsurvivors at 3 months after trial entry. (a) Creatinine in nonsurvivors (n = 31) and survivors (n = 112). (b) Renin in nonsurvivors (n = 31) and survivors (n = 108). (c) Atrial natriuretic peptide (ANP) in nonsurvivors (n = 31) and survivors (n = 108). (d) Syndecan-1 in nonsurvivors (n = 31) and survivors (n = 108). (e) Heart rate in nonsurvivors (n = 31) and survivors (n = 111). (f) Mean arterial pressure (MAP) in nonsurvivors (n = 31) and survivors (n = 111). Data presented as median values with Mann-Whitney statistical testing between groups, P values on figures. (g) Lowest daily paired systolic blood pressure recordings (with paired diastolic pressure) during the trial treatment period (mean and SD) for targeted albumin (n = 71) and standard care (n = 72) patients. (h) Heart rate variation during the trial treatment period (mean, SD) in targeted albumin (n = 71) and standard care (n = 72) patients.