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Effect of Albumin Use on Minimal Hepatic Encephalopathy in Patients With Prior Overt Hepatic Encephalopathy
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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.
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]).
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.
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
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.
Disclosure statements are available on the authors' profiles:
A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL studyJ. Hepatol. 2023 Feb 01;78(2)312-321, A Fagan, EA Gavis, ML Gallagher, T Mousel, B Davis, P Puri, RK Sterling, VA Luketic, H Lee, SC Matherly, AJ Sanyal, RT Stravitz, V Patel, MS Siddiqui, A Asgharpour, M Fuchs, L Thacker, JS Bajaj
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Many patients have persistent cognitive dysfunction and poor quality of life despite recovery from overt hepatic encephalopathy (HE) and treatment with lactulose and rifaximin.1 Although it is not well known, hydration can be an effective therapy for HE. Albumin infusions, specifically, are thought to have immune modulating properties. For this reason, Bajaj et al conducted the HEAL study. In a 6-week placebo-controlled, blinded trial, 48 patients were randomized 1:1 to receive either five weekly infusions of 1.5 g/kg of 25% intravenous human albumin solution or an equivalent volume of normal saline. The primary outcome was change in cognitive function. Quality of life and a host of other markers — ammonia, endothelial dysfunction, inflammatory cytokines — were also examined.
The headline result is that albumin was associated with improvement in cognitive function (albeit only in 29% of patients), psychosocial domains of quality of life, endothelial function, and inflammation. These results were observed without any differences in ammonia levels. Limitations of the study include the small sample size and the lack of clinical endpoints. In addition, the analytic plan focused primarily on within-group differences. Although albumin had more impressive pre–post improvements, it is not clear how many were significant when compared with the changes in the placebo arm.
The take-away messages are twofold. First, help your patients avoid dehydration, but weekly albumin infusions are not ready for prime time. Second, ammonia may not be the reason for persistent HE symptoms.
1. Riggio O, Ridola L, Pasquale C, et al. Evidence of persistent cognitive impairment after resolution of overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2011;9(2):181-183. https://www.cghjournal.org/article/S1542-3565(10)00977-8/fulltext