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Albumin for Liver-Brain Outcome Improvement Across Different Situations in Cirrhosis

  • Jasmohan S. Bajaj
    Correspondence
    Corresponding author. Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System¸ 1201 Broad Rock Blvd¸ Richmond, Virginia, USA 23249¸ Telephone: 804 675 5802¸ Fax: 804 675 5816¸
    Affiliations
    Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University and Central Virginia Veterans Healthcare System, Richmond, Virginia, USA
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Published:November 15, 2022DOI:https://doi.org/10.1016/j.jhep.2022.11.007

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      Linked Article

      • Albumin for cognitive impairment after TIPS: a road to be explored
        Journal of Hepatology
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          We read with interest the paper by Fagan et al in which authors aimed to assess the role of albumin infusion on Minimal Hepatic Encephalopathy (MHE) and Quality Of Life (QOL) in patients with previous Hepatic Encephalopathy (HE) 1. In this double-blind, placebo-controlled randomized clinical trial it has been demonstrated that albumin infusions were associated with improved cognitive function and psychosocial quality of life likely through amelioration of endothelial dysfunction. Authors interestingly enrolled patients at risk for bouts of HE: subjects with previous HE and cognitive impairment detected at psychometric tests and considered the resolution/amelioration of MHE/psichometric performance as a robust surrogate marker able both to identify patients with a worst outcome as well as subjects in which the positive effects of any given treatment could be evaluated.
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      • A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL study
        Journal of Hepatology
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          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.
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      Conflict of interest

      The HEAL trial was supported by an investigator initiated grant from Grifols to Dr Bajaj’s Institution
      We appreciate the findings and interpretation of the post-TIPS albumin infusion study that was sent as a letter by Nardelli et al in response to our trial
      • Fagan A.
      • Gavis E.A.
      • Gallagher M.L.
      • Mousel T.
      • Davis B.
      • Puri P.
      • et al.
      A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL study.
      ,
      • Nardelli S.
      • Gioia S.
      • Faccioli J.
      • Riggio O.
      • Ridola L.
      Albumin for cognitive impairment after TIPS: a road to be explored.
      . Their interesting findings complement our trial in a higher-risk population of patients with cirrhosis undergoing TIPS placement.
      As Nardelli and colleagues point out, there are several salient differences in our RCT and their experience but the most important one was that we required all patients in our trial to have minimal hepatic encephalopathy (MHE), which was only seen in about half of their pre-TIPS patients. We focused on MHE as the primary endpoint because cognitive impairment is associated with poor functioning and subsequent clinical outcomes such as overt HE and survival
      • Vilstrup H.
      • Amodio P.
      • Bajaj J.
      • Cordoba J.
      • Ferenci P.
      • Mullen K.D.
      • et al.
      Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.
      . We agree that longer-term studies should focus also on clinical outcomes but of late several regulatory agencies have noted endpoints related to quality of life or daily functioning as important markers.
      The peri-TIPS period is an excellent within-subject model for studying the impact of interventions to prevent overt HE in a compressed time period
      • Riggio O.
      • Nardelli S.
      • Moscucci F.
      • Pasquale C.
      • Ridola L.
      • Merli M.
      Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.
      . However, the changes in cardiovascular, blood flow, and the underlying reason for TIPS placement all influence the risk of HE development post-TIPS, which are distinct from the stable outpatient setting that was included in our trial. In addition, all our patients had prior overt HE episodes already on lactulose and/or rifaximin in contrast to the peri-TIPS patients. There is evidence that the post-TIPS change in brain function in those with lower brain reserve such as prior HE or alcohol is felt to a lower extent by patients than those with non-alcoholic etiologies
      • Ahluwalia V.
      • Wade J.B.
      • Moeller F.G.
      • White M.B.
      • Unser A.B.
      • Gavis E.A.
      • et al.
      The etiology of cirrhosis is a strong determinant of brain reserve: A multimodal magnetic resonance imaging study.
      . Therefore, the lack of medical HE therapy peri-TIPS could have affected these outcomes
      • Bureau C.
      • Thabut D.
      • Jezequel C.
      • Archambeaud I.
      • D'Alteroche L.
      • Dharancy S.
      • et al.
      The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.
      . Regardless, there was a relatively lower post-TIPS HE proportion found in their experience than published literature, which is encouraging
      • Riggio O.
      • Nardelli S.
      • Moscucci F.
      • Pasquale C.
      • Ridola L.
      • Merli M.
      Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt.
      .
      In conclusion, we agree with Nardelli et al that despite these differences, there are hints emerging that intravenous albumin therapy could have a role in improving liver-brain outcomes in patients with cirrhosis. Larger studies are needed to answer these very important questions.

      References

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        • Gavis E.A.
        • Gallagher M.L.
        • Mousel T.
        • Davis B.
        • Puri P.
        • et al.
        A double-blind randomized placebo-controlled trial of albumin in outpatients with hepatic encephalopathy: HEAL study.
        J Hepatol. 2022;
        • Nardelli S.
        • Gioia S.
        • Faccioli J.
        • Riggio O.
        • Ridola L.
        Albumin for cognitive impairment after TIPS: a road to be explored.
        J Hepatol. 2022;
        • Vilstrup H.
        • Amodio P.
        • Bajaj J.
        • Cordoba J.
        • Ferenci P.
        • Mullen K.D.
        • et al.
        Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver.
        Hepatology. 2014; 60: 715-735
      1. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims. [cited; Available from:.

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        The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt : A Randomized Controlled Trial.
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