Highlights
- •Baseline serum albumin per se should not guide the decision to start albumin therapy.
- •1-month on-treatment serum albumin levels predict survival and can be used to guide therapy.
- •The serum albumin target threshold to be pursued is 4.0 g/dl.
- •Baseline serum albumin and MELD score predict the achievement of this target.
- •A survival benefit is seen even when on-treatment serum albumin does not normalize.
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.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial.Lancet. 2018; 391: 2417-2429
- Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.J Hepatol. 2018; 69: 1250-1259
- Long-term administration of human albumin improves survival in patients with cirrhosis and refractory ascites.Liver Int. 2019; 39: 98-105
- Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis.Gastroenterology. 2019; 157: 149-162
- Assessing the sensitivity of methods for estimating principal causal effects.Stat Methods Med Res. 2015; 24: 657-674
- Performance of principal scores to estimate the marginal compliers causal effect of an intervention.Stat Med. 2016; 35: 752-767
- The NICE cost-effectiveness threshold: what it is and what that means.Pharmacoeconomics. 2008; 26: 733-744
- Survival and prognostic factors of cirrhotic patients with ascites: a study of 134 outpatients.Am J Gastroenterol. 1993; 88: 514-519
- Transection of the oesophagus for bleeding oesophageal varices.J Surg. 1973; 60: 646-649
- The effect of age on serum albumin in healthy males: report from the Normative Aging Study.J Gerontol. 1988; 43: M18-M20
- Posttranscriptional changes of serum albumin: clinical and prognostic significance in hospitalized patients with cirrhosis.Hepatology. 2014; 60: 1851-1860
- Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications.Hepatology. 2013; 58: 1836-1846
- Post-hoc data analysis: benefits and limitations.Curr Opin Allergy Clin Immunol. 2013; 13: 223-224
- The predictive approaches to treatment effect heterogeneity (PATH) statement.Ann Intern Med. 2020; 172: 35-45
- Prognosis Research Strategy (PROGRESS) 3: prognostic model research.PLoS Med. 2013; 10: e1001381
Article info
Publication history
Published online: August 24, 2020
Accepted:
August 17,
2020
Received in revised form:
July 10,
2020
Received:
January 28,
2020
Footnotes
Author names in bold designate shared co-first authorship
Identification
Copyright
© 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
