Albumin Injections Linked to Improved Brain Function, QOL in Patients With Liver Cirrhosis


Researchers also found an improvement in specialized blood markers focusing on inflammation, endothelial dysfunction, and albumin function in patients receiving weekly albumin injection.

Among patients with liver cirrhosis and persistent challenges with brain function, those who received weekly injections of albumin experienced better brain function and quality of life (QoL) compared with those who received placebo injections, according to a study published in the Journal of Hepatology.

The study also found albumin injections were associated with reductions in inflammation and other blood factors that may contribute to improved brain function and QoL.

Liver cirrhosis and severe liver disease can lead to hepatic encephalopathy (HE), leading to challenges with thinking and processing information and therefore leading to reduced health-related QoL (HRQoL). Even after recovering from overt HE, minimal HE (MHE) can persist, and there are limited treatment options.

In this double-blind, randomized, placebo-controlled trial, the authors randomized 48 participants 1:1 to receive albumin—a protein normally produced by the liver that is low in cirrhosis—or saline.

All participants were outpatients with liver cirrhosis and prior HE, MHE, or hypoalbuminemia already receiving HE treatment. Any patients already receivingregular intravenous (IV) albumin infusions were excluded.

For a 5-week period, 24 patients received weekly infusions of 25% IV albumin 1.5g/kg, while the other 24 received saline. After the 5-weeks (end of drug [EOD]), patients were also observed for 1 week post-infusion (end of study [EOS]).

The authors defined MHE using either Psychometric hepatic encephalopathy score (PHES), Stroop, or Critical clicker frequency (CFF). MHE and QOL were compared between baseline, EOD, and EOS using Sickness Impact profile (SIP)—total physical, and psychosocial domains—and serum, which took into account inflammation, endothelial dysfunction, and ischemia-modified albumin (IMA).

Albumin levels significantly increased and IMA decreased only in the albumin group at both EOD and EOS compared with baseline. The authors noted no evidence of alcohol misuse or changes medications throughout the 5-week period that would affect cirrhosis progression.

The albumin group also saw a significant improvement in overall and delta PHES scores, SIP total and psychosocial domains, and EncephalApp and CFF scores compared with placebo.

The authors also found an improvement in specialized blood markers focusing on inflammation, endothelial dysfunction, and albumin function in patients receiving weekly albumin injection compared with patients receiving saline.

There were also similar adverse events between the 2 groups, with Model for End-stage Liver Disease (MELD) scores and ammonia levels remaining stable between and within groups.

The authors mentioned 2 other trials on albumin injection for liver cirrhosis, but they were not specifically focused on cognitive impairment outcomes and did not ascertain patient-reported outcomes. However, the current study was narrowly focused on stable outpatients with prior HE who experienced persistent cognitive impairment despite receiving standard of care.

“Since these patients often have symptoms and HRQOL impairment that is disproportionately higher than their MELD score, they are not adequately prioritized for liver transplant,” the authors said. “Therefore, the improvement of these patient-reported outcomes in this population is novel and could alleviate this burden in this underserved population.”


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. 2022;S0168-8278(22)03116-6. doi:10.1016/j.jhep.2022.09.009

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