Long-term albumin administration improves survival in patients with decompensated cirrhosis: final results of the “ANSWER” study

Caraceni, Paolo; Riggio, Oliviero; Angeli, P.; Alessandria, Carlo; Neri, Sergio; Foschi, F.G.; Levantesi, Fabio; Airoldi, Aldo; Boccia, S.; Baroni, G. Svegliati; Fagiuoli, S.; Cozzolongo, Raffaele; Marco, V. Di; Sangiovanni, Vincenzo; Morisco, F.; Toniutto, Pierluigi; Gasbarrini, A.; Marco, Rosanna De; Leonardis, Francesco De; Cacciola, Irene; Elia, Giusy; Federico, Alessandro Di; Massironi, Sara; Guarisco, Riccardo; Marin, G.; Ballardini, G.; Rendina, M.; Nardelli, Silvia; Piano, Salvatore; Elia, Chiara; Prestianni, Loredana; Neri, Elga; Mastroianni, Alejandra; Cesarini, Lucia; Simone, L.; Marzioni, Marco; Magini, Giulia; Romanelli, Roberto Giulio; Zappimbulso, M.; Calvaruso, V.; Parrella, Giovanni; Caporaso, Nicola; Pugliese, Fabio; Tortora, A.; Pasquale, Chiara; Cavallin, M.; Andrealli, Alida; Fidone, Federica; Lanzi, Arianna; Vangeli, Marcello; Salerno, F.; Roncadori, Andrea; Tufoni, Manuel; Zaccherini, Giacomo; Bernardi, M.

doi:10.1016/s0168-8278(17)30449-x

Cited by 11 publications

(6 citation statements)

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“…5,6,22 However, differing results from recent well-conducted outpatient studies suggest patient response may not be uniform. 23,24 All patients in this single-arm study were treated with IV HAS, which appeared to have a beneficial immune effect throughout hospitalization by antagonizing PGE 2 effects. However, it is possible that the differing inflammatory responses observed associated with patients' 3-month outcome may represent albumin treatment "successes" and "failures".…”

Section: Discussionmentioning

confidence: 99%

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

Bécares

Härmälä

China

et al. 2020

Clinical Gastroenterology and Hepatology

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BACKGROUND & AIMS: Infection is a common cause of death in patients with cirrhosis. We investigated the association between the innate immune response and death within 3 months of hospitalization. METHODS: Plasma samples were collected on days 1, 5, 10, and 15 from participants recruited into the albumin to prevent infection in chronic liver failure feasibility study. Patients with acute decompensated cirrhosis were given albumin infusions at 10 hospitals in the United Kingdom. Data were obtained from 45 survivors and 27 non-survivors. We incubated monocyte-derived macrophages from healthy individuals with patients' plasma samples and measured activation following lipopolysaccharide administration, determined by secretion of tumor necrosis factor and soluble mediators of inflammation. Each analysis included samples from 4 to 14 patients. RESULTS: Plasma samples from survivors vs non-survivors had different inflammatory profiles. Levels of prostaglandin E2 were high at times of patient hospitalization and decreased with albumin infusions. Increased levels of interleukin 4 (IL4) in plasma collected at day 5 of treatment were associated with survival at 3 months. Incubation of monocyte-derived macrophages with day 5 plasma from survivors, pre-incubated with a neutralizing antibody against IL4, caused a significant increase in tumor necrosis factor production to the level of non-survivor plasma. Although baseline characteristics were similar, non-survivors had higher white cell counts and levels of C-reactive protein and renal dysfunction. CONCLUSIONS: We identified profiles of inflammatory markers in plasma that are associated with 3-month mortality in patients with acute decompensated cirrhosis given albumin. Increases in prostaglandin E2 might promote inflammation within the first few days after hospitalization, and increased levels of plasma IL4 at day 5 are associated with increased survival. Clinicaltrialsregister.

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Section: Discussionmentioning

confidence: 99%

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

Bécares

Härmälä

China

et al. 2020

Clinical Gastroenterology and Hepatology

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“…A large trial in Italy evaluating long-term administration of albumin in patients with AD showed an improvement in survival and a decrease in complications, such as hepatic encephalopathy, renal dysfunction, etc. [73]. Other smaller studies suggest the opposite and have even reported severe adverse events, e.g.…”

Section: Albumin As Attenuation Of Inflammationmentioning

confidence: 99%

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

2018

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Acute-on-chronic liver failure (ACLF) is considered a distinct syndrome in patients with liver disease, with systemic inflammation playing a central role. Portal hypertension (PHT) is also aggravated by inflammation and may subsequently impact the course of ACLF. PHT is more than just an increase in portal pressure in the portal venous system; it aggravates the course of liver disease and, thus, also facilitates the development of acute decompensation and ACLF. A critical mechanistic link between PHT and ACLF might be the gut-liver axis, which is discussed in this review.

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“…Attempts to substitute or cleanse albumin (via albumin dialysis or plasma exchange) might therefore prove interest and warrant further investigation. In favour of this premise is the recently presented ANSWER study [ 68 ]. This randomised, controlled trial of 440 patients with cirrhosis and uncomplicated ascites compared standard diuretic therapy with standard diuretic therapy plus human albumin (40 g intravenously twice weekly in the first two weeks and then once weekly).…”

Section: Other Partners In Crimementioning

confidence: 99%

Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough

Laleman

Clària

Merwe

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

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ACLF is a specific, but complex and multifactorial form of acute decompensation of cirrhosis and is characterized by an extraordinary dynamic natural course, rapidly evolving organ failure, and high short-term mortality. Dysbalanced immune function is central to its pathogenesis and outcome with an initial excessive systemic inflammatory response that drives organ failure and mortality. Later in its course, immuno-exhaustion/immunoparalysis prevails predisposing the patient to secondary infectious events and reescalation in end-organ dysfunction and mortality. The management of patients with ACLF is still poorly defined. However, as its pathophysiology is gradually being unravelled, potential therapeutic targets emerge that warrant further study such as restoring or substituting albumin via plasma exchange or via albumin dialysis and evaluating usefulness of TLR4 antagonists, modulators of gut dysbiosis (pre- or probiotics), and FXR-agonists.

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Long-term albumin administration improves survival in patients with decompensated cirrhosis: final results of the “ANSWER” study

Cited by 11 publications

References 0 publications

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

Immune Regulatory Mediators in Plasma from Patients With Acute Decompensation Are Associated With 3-Month Mortality

Gut-Liver Axis Links Portal Hypertension to Acute-on-Chronic Liver Failure

Systemic Inflammation and Acute-on-Chronic Liver Failure: Too Much, Not Enough

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