Albumin treatment regimen for type 1 hepatorenal syndrome: a dose–response meta-analysis

  • Salerno F, Navickis RJ, Wilkes MM.
  • BMC Gastroenterol. 2015 Nov 25;15:167.

This meta-analysis examines whether the dosing of albumin affects outcomes in type 1 hepatorenal syndrome (HRS). Most studies to date have focussed on the vasopressor component of treatment, while this study extracted data from those studies to determine whether there was a response to increased levels of albumin. They were able to demonstrate a statistically significant association between patients who received more albumin overall and 30-day survival (HR 1.15; 95% CI 1.02–1.31; p=0.023).

Hepatorenal syndrome is a form of functional severe renal failure in patients with advanced liver cirrhosis; it is typically diagnosed by excluding other causes. There are two variants: type 1 disease has a fast onset and is treatable, although has a high mortality rate – average survival if disease is untreated is 11 days, and with treatment approximately half of affected patients will survive; type 2 disease has a more insidious onset and a median survival of 6 months. Treatment is with vasopressors and albumin infusion, with evidence demonstrating that the combined action provides better clinical outcomes versus monotherapy with either alone. To date, most studies have centred on the role of the vasopressor, testing different formulations and doses. Hard evidence is generally lacking regarding the optimisation of the albumin infusion however – prompting the authors to initiate this meta-analysis.

Studies which evaluated albumin infusion with vasopressors were identified; specifically, data were needed on HRS reversal and/or survival time. Unfortunately, there were no randomised trials suitable for inclusion, so only observational trials were included. Suitable papers were scrutinised to eliminate any redundant data included in multiple sources. Numerous data were extracted regarding therapy strategy and outcomes. The hypothesis to be tested was that outcomes of type 1 HRS vary significantly as a result of albumin dose. Potentially confounding factors were controlled for using a Cox proportional hazards regression model.

A total of 19 studies published between 1999 and 2012 met the inclusion criteria, comprising 574 patients in total – the median number of patients per study was 24. Baseline characteristics were consistently reported; age, serum creatinine, bilirubin and albumin, and mean arterial pressure; a diverse range of clinical criteria were also available for the analysis. HRS reversal was defined as correction to a serum creatinine of <1.5 mg/dL (132 µmol/L). The pooled data suggested the overall percentage attaining HRS reversal was 49.5% (95% CI 40.0–59.1%). Time of survival data were reported in 15 studies (n=377); pooled survival was 50.6% at 30 days (95% CI 45.5–56.3%). It was noted that increments of 100 g in cumulative albumin dose were associated with significantly increased survival (HR 1.15; 95% CI 1.02–1.31; p=0.023). An association was also noted for 10 g increments of daily albumin, although this did not reach statistical significance.

Albumin treatment regimen for type 1 hepatorenal syndrome: a dose–response meta-analysis.

In their discussion, the authors highlight that this is the first clear data to discriminate between albumin doses. The outlook for survival in HRS has improved markedly, but there is still room for improvement with currently available therapies; a focus on optimisation of albumin dosing could improve outcomes further. The authors point to the homogenous definition for reversal of HRS as a strength of the study, alongside a robust sample size for those at risk of death. They were able to control for vasoconstrictor dose and type, treatment duration, baseline bloods as well as several other clinical factors. It was limited by not being designed from the start as a head-to-head comparison, and as such can only demonstrate an association rather than a causative relationship. It is remarked that longer survival may correspond to receiving more albumin overall, however survival was not associated with longer duration of treatment or larger cumulative doses of vasopressors. The survival benefits of albumin have been identified in a variety of settings related to severe liver disease – all suggesting it is a useful strategy for patients with decompensated cirrhosis. There were few adverse events identified that were attributed to albumin therapy.

This study does not provide a basis for a rework of clinical protocols, however it does suggest a relationship between the administration of albumin and increased survival that should be further investigated. The study forms the basis for further confirmatory trials to demonstrate whether causation exists. For a condition such as HRS with a high mortality rate, every percentage point that survival is increased has a substantial impact on patients, and optimisation of treatment is a key strategy to improving care.

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