A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy : HEAL study
Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved..
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.
| Errataetall: |
CommentIn: J Hepatol. 2023 Mar;78(3):e96-e97. - PMID 36216135 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Journal of hepatology - 78(2023), 2 vom: 15. Feb., Seite 312-321 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Fagan, Andrew [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.01.2023 Date Revised 03.03.2023 published: Print-Electronic ClinicalTrials.gov: NCT03585257 CommentIn: J Hepatol. 2023 Mar;78(3):e96-e97. - PMID 36216135 Citation Status MEDLINE |
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| doi: |
10.1016/j.jhep.2022.09.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346690420 |
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| 100 | 1 | |a Fagan, Andrew |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy |b HEAL study |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 23.01.2023 | ||
| 500 | |a Date Revised 03.03.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT03585257 | ||
| 500 | |a CommentIn: J Hepatol. 2023 Mar;78(3):e96-e97. - PMID 36216135 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a 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 | ||
| 520 | |a 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]) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CLINICAL TRIALS REGISTRATION: www | ||
| 520 | |a CLINICALTRIALS: gov NCT03585257 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 4 | |a Cirrhosis | |
| 650 | 4 | |a EncephalApp | |
| 650 | 4 | |a cognitive dysfunction | |
| 650 | 4 | |a endothelial dysfunction | |
| 650 | 4 | |a health-related quality of life | |
| 650 | 4 | |a inflammation | |
| 650 | 7 | |a Biomarkers |2 NLM | |
| 650 | 7 | |a Serum Albumin |2 NLM | |
| 700 | 1 | |a Gavis, Edith A |e verfasserin |4 aut | |
| 700 | 1 | |a Gallagher, Mary Leslie |e verfasserin |4 aut | |
| 700 | 1 | |a Mousel, Travis |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Puri, Puneet |e verfasserin |4 aut | |
| 700 | 1 | |a Sterling, Richard K |e verfasserin |4 aut | |
| 700 | 1 | |a Luketic, Velimir A |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Hannah |e verfasserin |4 aut | |
| 700 | 1 | |a Matherly, Scott C |e verfasserin |4 aut | |
| 700 | 1 | |a Sanyal, Arun J |e verfasserin |4 aut | |
| 700 | 1 | |a Stravitz, R Todd |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Vaishali |e verfasserin |4 aut | |
| 700 | 1 | |a Siddiqui, Mohammad S |e verfasserin |4 aut | |
| 700 | 1 | |a Asgharpour, Amon |e verfasserin |4 aut | |
| 700 | 1 | |a Fuchs, Michael |e verfasserin |4 aut | |
| 700 | 1 | |a Thacker, Leroy |e verfasserin |4 aut | |
| 700 | 1 | |a Bajaj, Jasmohan S |e verfasserin |4 aut | |
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