Highlights
- •Persistent cognitive impairment affects quality of life in individuals with cirrhosis who have had prior episodes of HE.
- •We found in a randomized-controlled trial that weekly albumin infusions improved cognition vs. placebo.
- •Albumin improved quality of life, endothelial dysfunction, and inflammation.
- •Higher albumin levels and cognitive benefit persisted even after infusions had stopped.
Background & Aims
Even after recovery from overt hepatic encephalopathy (HE), minimal HE (MHE), which
impairs quality of life (QoL), can persist. A double-blind, placebo-controlled randomized
clinical trial was performed to determine the impact of albumin vs. saline on MHE and QoL in individuals with prior HE already on standard of care.
Methods
Outpatients with cirrhosis and prior HE, MHE and hypoalbuminemia already on treatment
for HE were included. Patients on regular IV albumin infusions were excluded. Participants
were randomized 1:1 to receive either weekly infusions of 25% IV albumin 1.5 g/kg
or saline over 5 weeks. MHE was defined using either psychometric hepatic encephalopathy
score (PHES), Stroop or critical clicker frequency. MHE, QoL (based on sickness impact
profile [SIP] total, physical, psychosocial domain) and serum markers (inflammation,
endothelial dysfunction, and ischemia-modified albumin) were compared between baseline,
the final infusion visit (end-of-drug [EOD]) and 1-week post final infusion (end-of-study
[EOS]).
Results
Forty-eight (24/group) participants were randomized and balanced (including by HE
medication use) at baseline. Adverse events were similar, with MELD and ammonia remaining
stable between/within groups. Albumin levels increased and ischemia-modified albumin
decreased only in the albumin group at EOD and EOS vs. baseline. PHES and Stroop MHE reversal and improvement were greater in the albumin
group at EOD and persisted at EOS. SIP total and psychosocial, but not physical, domain
improved only in the albumin group at EOD and EOS vs. baseline. A significant reduction in IL-1β and endothelial dysfunction markers was
also observed in the albumin group.
Conclusion
In a double-blind, placebo-controlled trial of outpatients with cirrhosis, prior HE
and current MHE, albumin infusions were associated with improved cognitive function
and psychosocial QoL, likely due to amelioration of endothelial dysfunction.
Clinical trials registration
www.clinicaltrials.gov NCT03585257.
Impact and implications
Even after recovery from overt hepatic encephalopathy (HE), minimal HE (MHE), which
impairs quality of life, can persist. We found that intravenous albumin infusions
were associated with improved cognitive function and psychosocial quality of life,
likely owing to amelioration of endothelial dysfunction, compared to placebo in outpatients
with prior HE and current MHE. In patients who continue to demonstrate cognitive dysfunction
and impaired quality of life despite standard of care therapy for HE, albumin infusions
could be considered if these results are validated.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: September 21, 2022
Accepted:
September 13,
2022
Received in revised form:
August 26,
2022
Received:
July 29,
2022
Identification
Copyright
© 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
