On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Caraceni, Paolo; Tufoni, Manuel; Zaccherini, Giacomo; Riggio, Oliviero; Angeli, Paolo; Alessandria, Carlo; Neri, Sergio; Foschi, Francesco Giuseppe; Levantesi, Fabio; Airoldi, Aldo; Simone, L.; Svegliati‐Baroni, Gianluca; Fagiuoli, S.; Laffi, Giacomo; Cozzolongo, Raffaele; Marco, V. Di; Sangiovanni, Vincenzo; Morisco, Filomena; Toniutto, Pierluigi; Gasbarrini, Antonio; Marco, Rosanna De; Piano, Salvatore; Nardelli, Silvia; Elia, Chiara; Roncadori, Andrea; Baldassarre, Maurizio; Bernardi, Mauro; Domenicali, Marco; Giannone, Ferdinando; Antognoli, Agnese; Merli, Manuela; Pasquale, Chiara; Gioia, Stefania; Fasolato, S.; Sticca, A.; Campion, Daniela; Risso, À.; Saracco, Giorgio Maria; Prestianni, Loredana; Fidone, Federica; Maiorca, D.; Rizzotto, Agostino; Cappa, Federica Mirici; Lanzi, Arianna; Neri, Elga; Visani, Anna; Mastroianni, Antonio; Perricone, Giovanni; Alberti, A.; Cesarini, Lucia; Mazzarelli, Chiara; Vangeli, Marcello; Viganò, R.; Marzioni, Marco; Capretti, Francesca; Kostandini, Alba; Magini, Giulia; Colpani, M.; Gabbani, Tommaso; Marsico, Maria De; Zappimbulso, M.; Petruzzi, Josè; Calvaruso, V.; Parrella, Giovanni; Caporaso, Nicola; Auriemma, Francesco; Guarino, Maria; Pugliese, Fabio; Tortora, Annalisa; Leo, Pietro; Angélico, M.; Leonardis, Francesco De; Pecchioli, A.; Rossi, Piera; Raimondo, Giovanni; Cacciola, Irene; Elia, G.; Negri, Elisa; Dallio, Marcello; Loguercio, Carmelina; Federico, Alessandro Di; Conte, Dario; Massironi, Sara; Celli, Giorgio Ballardini Natascia; Rendina, Maria; Bringiotti, R.; Castellaneta, N.M.; Salerno, Francesco; Boccia, S.; Guarisco, Riccardo; Galioto, Alessandra; Cavallin, M.; Andrealli, Alida

doi:10.1016/j.jhep.2020.08.021

Cited by 47 publications

(36 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…5 A subsequent post hoc analysis of the latter trial showed that the serum albumin concentration reached after 1 month of treatment predicted the probability of 18-month overall survival, which was greater than 90% in patients with serum albumin > − 4 g/dl. 82 The importance of increasing the serum albumin concentration beyond a certain level is further supported by 2 other pieces of evidence. In the pilot-PRECIOSA study, an improvement in circulatory dysfunction and systemic inflammation was achieved only in the group of patients receiving human albumin at the higher dose (1.5 g/kg b.w.…”

Section: Oncotic Activitymentioning

confidence: 88%

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

Caraceni

Abraldes

Ginès

et al. 2021

Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing.

show abstract

Section: Oncotic Activitymentioning

confidence: 88%

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

Caraceni

Abraldes

Ginès

et al. 2021

Journal of Hepatology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In contrast, serum albumin concentration rose by 0.7–0.8 g/L to almost 4 g/dL in the ANSWER study [ 117 ]. A post-hoc analysis of the latter trial showed that on-treatment serum albumin concentration at one month predicts the probability of 18-month overall survival, which was greater than 90% in patients whose serum albumin concentration reached levels 4 g/dL [ 120 ]. Baseline serum albumin and MELD score value independently predicted the achievement of this threshold.…”

Section: Pathophysiological Treatmentsmentioning

confidence: 99%

“…Baseline serum albumin and MELD score value independently predicted the achievement of this threshold. This would imply that patients with severe hypoalbuminema and very high MELD score should receive greater amounts of HA to achieve the best results [ 120 ]. Two other pieces of evidence support the importance of steadily increasing serum albumin concentration beyond a certain level.…”

Section: Pathophysiological Treatmentsmentioning

confidence: 99%

Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents

Zaccherini

Tufoni

Bernardi

et al. 2021

JCM

Self Cite

View full text Add to dashboard Cite

The current therapeutic strategies for the management of patients with cirrhosis rely on the prevention or treatment of specific complications. The removal of the causative agents (i.e., viruses or alcohol) prevents decompensation in the vast majority of patients with compensated cirrhosis. In contrast, even when etiological treatment has been effective, a significant proportion of patients with decompensated cirrhosis remains at risk of further disease progression. Therefore, therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis could represent a new approach for the management of these severely ill patients. Some of the interventions currently employed for treating or preventing specific complications of cirrhosis or used in other diseases (i.e., poorly absorbable oral antibiotics, statins, albumin) have been proposed as potential disease-modifying agents in cirrhosis (DMAC) since clinical studies have shown their capacity of improving survival. Additional multicenter, large randomized clinical trials are awaited to confirm these promising results. Finally, new drugs able to antagonize key pathophysiological mechanisms are under pre-clinical development or at the initial stages of clinical assessment.

show abstract

“…The open‐label design was the major limitation of this trial, since weekly albumin administration necessitated frequent nursing visits in the intervention group, and there was no blinding of outcome assessments. In a subsequent post hoc analysis of the results of the ANSWER investigation, a one‐month albumin threshold of 4 g/dl was the single best point estimate of survival, but any value in the range of 2.5–4.5 g/dl was discriminant for a survival benefit 23 . The investigators of the ANSWER trial and post hoc analysis noted the need for further studies evaluating subgroups of patients most likely to benefit from albumin administration, as well as external validation and risk prediction of albumin concentration threshold.…”

Section: Commentmentioning

confidence: 99%

Albumin for cirrhosis‐related complications

Erstad

2021

J Clin Pharm Ther

View full text Add to dashboard Cite

What is known and objective The purpose of this paper was to discuss the limitations of the studies serving as the evidence for recommendations in clinical practice guidelines concerning albumin use for cirrhosis‐related complications, review relevant studies published since the guidelines and suggest directions for future investigations. Comment There are no recent comprehensive clinical practice guidelines concerning albumin. Instead, more recent albumin guidelines reflect areas of specialty practice such as those by American and European associations for the study of the liver and liver disease. Studies published since the guidelines are useful for helping to define the most appropriate indications for albumin with respect to cirrhosis‐related complications, as well as directions for future research. What is new and conclusion Albumin has a long history of attempts to define appropriate uses by meta‐analysis, but given the high cost and episodic shortages of albumin, there is a need for adequately powered randomized controlled trials using current state‐of‐the‐art care evaluating the use of albumin to prevent or treat cirrhosis‐related complications.

show abstract

On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Cited by 47 publications

References 14 publications

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

Prevention of Cirrhosis Complications: Looking for Potential Disease Modifying Agents

Albumin for cirrhosis‐related complications

Contact Info

Product

Resources

About