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).
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.
Bernardi M, Moreau R, Angeli P, Schnabl B, Arroyo V. Mechanisms of decompensation and organ failure in cirrhosis: From peripheral arterial vasodilation to systemic inflammation hypothesis. J Hepatol. 2015;63:1272‒84.
D’Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44:217–31.
Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology. 2013;58:1836–46.
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.
GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016b;388:1459‒1544.
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.
Alternatively login via
Back to epgonline.org