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To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S0140-6736(18)30840-7 Byline: Paolo Caraceni, MD (a), Oliviero Riggio, MD (b), Prof Paolo Angeli, PhD (c), Carlo Alessandria, MD (d), Sergio Neri, MD (e), Francesco G Foschi, MD (f), Fabio Levantesi, MD (g), Aldo Airoldi, MD (h), Sergio Boccia, MD (i), Gianluca Svegliati-Baroni, MD (j), Stefano Fagiuoli, MD (k), Roberto G Romanelli, PhD (l), Raffaele Cozzolongo, MD (m), Prof Vito Di Marco, MD (n), Vincenzo Sangiovanni, MD (o), Filomena Morisco, MD (p), Pierluigi Toniutto, MD (q), Annalisa Tortora, MD (r), Rosanna De Marco, MD (s), Prof Mario Angelico, MD (t), Irene Cacciola, PhD (u), Gianfranco Elia, MD (v), Alessandro Federico, PhD (w), Sara Massironi, PhD (x), Riccardo Guarisco, MD (y), Alessandra Galioto, MD (z), Giorgio Ballardini, MD (aa), Maria Rendina, MD (ab), Silvia Nardelli, MD (b), Salvatore Piano, PhD (c), Chiara Elia, MD (d), Loredana Prestianni, MD (e), Federica Mirici Cappa, PhD (f), Lucia Cesarini, MD (h), Loredana Simone, MD (i), Chiara Pasquale, MD (b), Marta Cavallin, MD (c), Alida Andrealli, MD (d), Federica Fidone, MD (e), Matteo Ruggeri, PhD (ac), Andrea Roncadori, BSc (ad), Maurizio Baldassarre, PhD (a), Manuel Tufoni, MD (a), Giacomo Zaccherini, MD (a), Prof Mauro Bernardi, MD [mauro.bernardi@unibo.it] (a,*), Marco Domenicali, Ferdinando A Giannone, Manuela Merli, Stefania Gioia, Silvano Fasolato, Antonietta Sticca, Daniela Campion, Alessandro Risso, Giorgio M Saracco, Daniela Maiorca, Agostino Rizzotto, Arianna Lanzi, Elga Neri, Anna Visani, Antonio Mastroianni, Alberto B Alberti, Chiara Mazzarelli, Marcello Vangeli, Marco Marzioni, Francesca Capretti, Alba Kostandini, Giulia Magini, Maria Colpani, Giacomo Laffi, Tommaso Gabbani, Maria Marsico, Marianna Zappimbulso, Jose Petruzzi, Vincenza Calvaruso, Giovanni Parrella, Nicola Caporaso, Francesco Auriemma, Maria Guarino, Fabio Pugliese, Antonio Gasbarrini, Pietro Leo, Francesco De Leonardis, Alessandra Pecchioli, Piera Rossi, Giovanni Raimondo, Elisa Negri, Marcello Dallio, Carmelina Loguercio, Dario Conte, Natascia Celli, Roberto Bringiotti, Nicola M Castellaneta, Francesco Salerno Summary Background Evidence is scarce on the efficacy of long-term human albumin (HA) administration in patients with decompensated cirrhosis. The human Albumin for the treatmeNt of aScites in patients With hEpatic ciRrhosis (ANSWER) study was designed to clarify this issue. Methods We did an investigator-initiated multicentre randomised, parallel, open-label, pragmatic trial in 33 academic and non-academic Italian hospitals. We randomly assigned patients with cirrhosis and uncomplicated ascites who were treated with anti-aldosteronic drugs ([greater than or equal to]200 mg/day) and furosemide ([greater than or equal to]25 mg/day) to receive either standard medical treatment (SMT) or SMT plus HA (40 g twice weekly for 2 weeks, and then 40 g weekly) for up to 18 months. The primary endpoint was 18-month mortality, evaluated as difference of events and analysis of survival time in patients included in the modified intention-to-treat and per-protocol populations. This study is registered with EudraCT, number 2008--000625--19, and ClinicalTrials.gov, number NCT01288794. Findings From April 2, 2011, to May 27, 2015, 440 patients were randomly assigned and 431 were included in the modified intention-to-treat analysis. 38 of 218 patients died in the SMT plus HA group and 46 of 213 in the SMT group. Overall 18-month survival was significantly higher in the SMT plus HA than in the SMT group (Kaplan-Meier estimates 77% vs 66%; p=0*028), resulting in a 38% reduction in the mortality hazard ratio (0*62 [95% CI 0*40--0*95]). 46 (22%) patients in the SMT group and 49 (22%) in the SMT plus HA group had grade 3--4 non-liver related adverse events. Interpretation In this trial, long-term HA administration prolongs overall survival and might act as a disease modifying treatment in patients with decompensated cirrhosis. Funding Italian Medicine Agency. Author Affiliation: (a) Department of Medical and Surgical Sciences, and Center for Applied Biomedical Research, University of Bologna, Bologna, Italy (b) Department of Clinical Medicine, Sapienza University of Rome, Rome, Italy (c) Unit of Internal Medicine and Hepatology, Department of Medicine, University of Padua, Padua, Italy (d) Division of Gastroenterology and Hepatology, Citta della Salute e della Scienza Hospital, University of Turin, Turin, Italy (e) Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy (f) Internal Medicine, Hospital of Faenza, Azienda Unita Sanitaria Locale of Romagna, Faenza, Italy (g) Internal Medicine, Hospital of Bentivoglio, AUSL of Bologna, Bologna, Italy (h) Liver Unit, Department of Hepatology and Gastroenterology, Niguarda Hospital, Milan, Italy (i) Gastroenterology Unit, University Hospital, Ferrara, Italy (j) Department of Gastroenterology, Polytechnic University of Marche, Ancona, Italy (k) Gastroenterology and Transplant Hepatology, Papa Giovanni XXIII Hospital, Bergamo, Italy (l) Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy (m) Division of Gastroenterology, National Institute of Gastroenterology S De Bellis, Castellana Grotte (Bari), Italy (n) Unit of Gastroenterology and Hepatology, Biomedical Department of Internal and Specialistic Medicine, University of Palermo, Palermo, Italy (o) Azienda Ospedaliera di Rilievo Nazionale dei Colli, Cotugno Hospital of Naples, Naples, Italy (p) Gastroenterology Unit, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy (q) Internal Medicine, Department of Medical Area, University of Udine, Udine, Italy (r) Gastroenterology, Gemelli Foundation, Catholic University, Rome, Italy (s) Gastroenterology Unit, Hospital of Cosenza, Cosenza, Italy (t) Liver Unit, Tor Vergata University, Rome, Italy (u) Division of Clinical and Molecular Hepatology, University Hospital of Messina, Messina, Italy (v) Infectious Diseases and Hepatology, University Hospital of Parma, Parma, Italy (w) Department of Clinical and Experimental Internal Medicine, University of Campania Luigi Vanvitelli, Naples, Italy (x) Gastroenterology and Endoscopy Unit, Foundation Istituto di Ricovero e Cura a Carattere Scientifico Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy (y) Internal Medicine, S Sebastiano General Hospital, Frascati (Rome), Italy (z) Internal Medicine, Hospital of Dolo, Azienda Unita Locale Socio-sanitaria Serenissima, Mestre, Italy (aa) Internal Medicine, Hospital of Rimini, AUSL of Romagna, Rimini, Italy (ab) Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy (ac) Graduate School of Health Economics and Management, Catholic University, Rome, Italy (ad) Cineca Interuniversity Consortium, Bologna, Italy * Correspondence to: Prof Mauro Bernardi, Department of Medical and Surgical Sciences, University of Bologna, S Orsola-Malpighi University Hospital, 40138 Bologna, Italy (footnote)[Dagger] Investigators listed at the end of the paper