Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

  • Caraceni P, Riggio O, Angeli P, Alessandria C, Neri S, Foschi FG, et al.
  • Lancet 2018;391:2417–29.

Long-term human albumin administration was investigated as a potential disease-modifying agent in patients with decompensated cirrhosis. The human AlbumiN for the treatment of aScites in patients With hEpatic ciRrhosis (ANSWER) trial showed that a pathophysiological therapy for ascites resulted in better outcomes than traditional symptomatic treatment. This is an important study that will stimulate further research and eventually change practice.

Cirrhosis of the liver is a leading cause of disability and mortality worldwide (GBD, 2016a;b). The final stage of the disease, decompensated cirrhosis, has a poor prognosis, with a median survival of about 2 years. Patients have a poor quality of life, with repeated hospital admissions and associated high healthcare costs (D’Amico et al., 2006; Stepanova et al., 2017).

The current management of decompensated cirrhosis is focussed on relieving symptoms. Human albumin is administered in ascites for its oncotic properties as a plasma volume expander. However, human albumin has other, non-oncotic, properties. These include antioxidant and scavenging activities, regulating endothelial function and inflammatory and immune responses, and the binding and transport of exogenous and endogenous substances (Garcia-Martinez et al., 2013). These properties may provide the potential for human albumin (HA) to target several pathophysiological mechanisms underlying decompensated cirrhosis (Bernardi et al., 2015).

Although the long-term administration of HA to patients with ascites has been debated for many years, there have only been two prospective controlled trials, both small, open-label, and by the same centre. One of these trials suggested that long-term HA might reduce the risk of developing ascites and hospital readmissions (Gentilini et al., 1999), though with no effect on survival, while the other trial reported an improvement in transplant-free survival (Romanelli et al., 2006).

It was in this context that the ANSWER trial was set up (Figure 1).

Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial

Figure 1. Summary of The human AlbumiN for the treatment of aScites in patients With hEpatic ciRrhosis (ANSWER) trial (Caraceni et al., 2018).

While research is needed to identify patient subgroups likely to benefit from long-term HA, this trial is an important study that may eventually prompt a change in clinical practice to a more comprehensive approach aimed at slowing down the progression of the disease. 

References

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GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016a;388:1545–602.

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Gentilini P, Casini-Raggi V, Di Fiore G, Romanelli RG, Buzzelli G, Pinzani M, et al. Albumin improves the response to diuretics in patients with cirrhosis and ascites: results of a randomized, controlled trial. J Hepatol. 1999;30:639–45.

Romanelli RG, La Villa G, Barletta G, Vizzutti F, Lanini F, Arena U, et al. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. World J Gastroenterol. 2006;12:1403–7.

Stepanova M, De Avila L, Afendy M, Younossi I, Pham H, Cable R, et al. Direct and indirect economic burden of chronic liver disease in the United States. Clin Gastroenterol Hepatol. 2017;15:759–66.

 

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