TY - JOUR
T1 - On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites
AU - ANSWER Study Investigators
AU - Caraceni, Paolo
AU - Tufoni, Manuel
AU - Zaccherini, Giacomo
AU - Riggio, Oliviero
AU - Angeli, Paolo
AU - Alessandria, Carlo
AU - Neri, Sergio
AU - Foschi, Francesco G.
AU - Levantesi, Fabio
AU - Airoldi, Aldo
AU - Simone, Loredana
AU - Svegliati-Baroni, Gianluca
AU - Fagiuoli, Stefano
AU - Laffi, Giacomo
AU - Cozzolongo, Raffaele
AU - Di Marco, Vito
AU - Sangiovanni, Vincenzo
AU - Morisco, Filomena
AU - Toniutto, Pierluigi
AU - Gasbarrini, Antonio
AU - De Marco, Rosanna
AU - Piano, Salvatore
AU - Nardelli, Silvia
AU - Elia, Chiara
AU - Roncadori, Andrea
AU - Baldassarre, Maurizio
AU - Bernardi, Mauro
AU - Domenicali, Marco
AU - Giannone, Ferdinando A.
AU - Antognoli, Agnese
AU - Merli, Manuela
AU - Pasquale, Chiara
AU - Gioia, Stefania
AU - Fasolato, Silvano
AU - Sticca, Antonietta
AU - Campion, Daniela
AU - Risso, Alessandro
AU - Saracco, Giorgio M.
AU - Prestianni, Loredana
AU - Fidone, Federica
AU - Maiorca, Daniela
AU - Rizzotto, Agostino
AU - Mastroianni, Antonio
AU - Zappimbulso, Marianna
AU - Auriemma, Francesco
AU - Guarino, Maria
AU - Conte, Dario
AU - Massironi, Sara
AU - Rendina, Maria
AU - Salerno, Francesco
N1 - Funding Information:
The ANSWER trial was funded by the competitive grant FARM6P824B from the Italian Medicine Agency .
Funding Information:
PC is part of the speakers' bureau for Grifols SA, Octapharma AG, Baxalta, and Kedrion Biopharma, is consultant for Kedrion Biopharma, is on the advisory board for Grifols SA, and has a research grant from Octapharma AG. MT is part of the speakers' bureau for Grifols SA and Octapharma AG. GZ is part of the speakers' bureau for Octapharma. OR is part of speakers' bureau for Baxalta. PA is part of the speakers' bureau for Baxalta and Kedrion Biopharma. PT is part of the speakers' bureau for Grifols and Kedrion Biopharma. MBa is part of the speakers' bureau Octapharma AG. MBe is part of the speakers' bureau for Grifols SA, Octapharma AG, Baxalta, CLS Behring GmbH, and PPTA, and is a consultant for CLS Behring GmbH, Grifols SA and Baxalta. All other authors have no competing interests.
Funding Information:
The trial was funded by the competitive peer-reviewed grant FARM6P824B from the Italian Medicine Agency. We thank the Italian Association for the Study of the Liver, the Italian Society of Gastroenterology, and the Italian Association of Hospital Gastroenterologists for their endorsement of this study. The methodological advice from Dr. Agostino Colli is gratefully acknowledged. We also thank the study patients and their relatives for their participation, and the physicians and nursing staff of the participating centres for their cooperation.
Publisher Copyright:
© 2020 European Association for the Study of the Liver
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.
AB - Background & Aims: The ANSWER study reported that long-term albumin administration in patients with cirrhosis and uncomplicated ascites improves survival. During treatment, serum albumin increased within a month and remained stable thereafter. In this post hoc analysis, we aimed to determine whether on-treatment serum albumin levels could guide therapy. Methods: Logistic regression was used to assess the association between baseline serum albumin and mortality, as well as to determine on-treatment factors associated with mortality and to predict the achievement of a given on-treatment serum albumin level. Survival was assessed by Kaplan-Meier estimates and second-order polynomial regression. Patients whose on-treatment serum albumin remained below normal were compared with a subset of patients from the control arm matched by principal score. Results: Baseline serum albumin was closely associated with 18-month mortality in untreated patients; albumin treatment almost effaced this relationship. On-treatment serum albumin and MELD-Na at month 1 were the sole independent variables associated with mortality. Second-order polynomial regression revealed that survival improved in parallel with increased 1-month on-treatment serum albumin. Kaplan-Meier estimations showed that any value of 1-month on-treatment serum albumin (0.1 g/dl intervals) in the range 2.5–4.5 g/dl discriminated patient survival. In the normal range of serum albumin, the best discriminant value was 4.0 g/dl. Compared to untreated patients, survival even improved in patients whose on-treatment serum albumin remained below normal. Conclusion: Baseline serum albumin per se should not guide the decision to start albumin therapy. Conversely, 1-month on-treatment serum albumin levels are strongly associated with outcomes and could guide the use of albumin – 4.0 g/dl being the target threshold. However, even patients whose serum albumin remains below normal benefit from long-term albumin administration. Lay summary: The ANSWER study has shown that long-term albumin administration improves survival and prevents the occurrence of major complications in patients with cirrhosis and ascites. This study shows that the achievement of these beneficial effects is related to a significant increase in serum albumin concentration. Even though the best results follow the achievement of a serum albumin concentration of 4 g/dl, a survival benefit is also achieved in patients who fail to normalise serum albumin.
KW - Ascites
KW - Cirrhosis
KW - Complications
KW - Serum albumin
KW - Survival
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U2 - 10.1016/j.jhep.2020.08.021
DO - 10.1016/j.jhep.2020.08.021
M3 - Article
C2 - 32853747
AN - SCOPUS:85094839223
VL - 74
SP - 340
EP - 349
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 2
ER -