Albumin Infusions Improved Cognition, QOL in Patients with Minimal HE

Albumin infusions can improve cognitive function and quality of life in patients with cirrhosis, current minimal HE, or prior HE.

Compared with placebo, albumin infusions improved cognitive impairments and quality of life (QOL) in patients with symptoms of minimal hepatic encephalopathy (MHE), according to findings published in the Journal of Hepatology.

Researchers conducted a randomized, placebo-controlled trial from August 2018 to May 2022 with interruption during 2020 due to the COVID pandemic. Forty-eight patients with cirrhosis with prior history of HE and current minimal HE (MHE) and hypoalbuminemia were randomly assigned to 2 groups — the albumin treatment group, who received 25% intravenous albumin dosed at 1.5g/kg and administered once per week for 5 weeks and the placebo group, who received an equivalent saline dose.

The researchers analyzed the data they obtained to determine the effect of IV albumin infusions compared with placebo on MHE symptoms and QOL.

Researchers assessed patient cognitive impairment using the Psychometric Hepatic Encephalopathy Score (PHES<4), the Stroop test based on OffTime and OnTime norms, and the Critical Flicker Frequency (CFF <39Hz).

Researchers also assessed QOL using the Sickness Impact Profile (SIP) and performed serological testing for inflammatory factors, endothelial dysfunction, and ischemia-modified albumin (IMA) levels. Assessments occurred at baseline, the end of drug (EOD) administration at week 5, and the end of the study (EOS) 1 week later at week 6.

This improvement is accompanied by changes related to improvement in endothelial dysfunction, systemic inflammatory milieu, and albumin functionality.

Patients receiving the albumin infusions demonstrated increased albumin levels and decreased IMA levels at EOD administration and EOS compared with baseline levels and with the placebo group.

Improvement and reversal of MHE-related cognitive impairments as evidenced by the PHES and Stroop test (EncephalApp) scores occurred in approximately 29% and 71% of the patients, respectively. These effects persisted more in the albumin therapy group compared with the placebo group.

Those receiving albumin therapy also demonstrated and maintained improved QOL scores on the SIP total and psychosocial domains compared with the placebo group at weeks 5 and 6.

In the albumin group, the researchers observed significant serological reductions in the inflammatory cytokine, interleukin-1-beta (IL-1β), and endothelial dysfunction markers, including asymmetric dimethyl arginine (ADMA) and soluble intercellular adhesion molecule-1 (sICAM-1), at weeks 5 and 6.

“A 5-week course of albumin therapy improves cognitive performance and psychosocial health-related quality of life compared to placebo that persists up to a week after albumin discontinuation,” the study authors wrote. “This improvement is accompanied by changes related to improvement in endothelial dysfunction, systemic inflammatory milieu, and albumin functionality.”

Study limitations included the modest sample size, short follow-up duration, and lack of assessment of overt HE relapses and hospitalizations.


Fagan A, Gavis EA, Gallagher ML, et al. A double-blind randomized placebo-controlled trial of albumin in patients with hepatic encephalopathy: HEAL study. J Hepatol. Published online September 21, 2022:S0168-8278(22)03116-6. doi:10.1016/j.jhep.2022.09.009