In decompensated cirrhosis, targeted albumin infusions did not improve an in-hospital composite outcome at 15 days

The results of this randomized trial should not discourage clinicians from using albumin for recognized indications, but they do not support targeting an arbitrary serum albumin level, an ACP Journal Club commentary said.

No significant benefit was seen in a recent British study of targeted albumin in hospitalized patients with decompensated cirrhosis. The unblinded trial included patients who had a serum albumin level less than 30 g/L: 380 randomized to targeted albumin therapy and 397 to standard care. There was no difference between groups on the primary end point of new infection, kidney dysfunction, or death, but severe or life-threatening serious adverse events were more common in the targeted albumin group, leading the authors to conclude that infusions to increase the albumin level to a target of 30 g/L or more was not more beneficial than the current standard of care.

The study was published on March 4 by the New England Journal of Medicine and summarized in the March 10 ACP Hospitalist Weekly. The following commentary by Julian Hercun, MD, and Averell H. Sherker, MD, appeared in the ACP Journal Club section of the August Annals of Internal Medicine.

Hypoalbuminemia has long been recognized as a prognostic marker in cirrhosis and is an integral part of the widely used Child–Pugh classification. Further, albumin infusions are standard of care for managing spontaneous bacterial peritonitis, large-volume paracentesis, and hepatorenal syndrome (HRS). It remains controversial whether albumin infusions are otherwise beneficial for treating decompensated cirrhosis.

In the unblinded randomized controlled ATTIRE trial, China and colleagues evaluated albumin infusions in hospitalized patients with decompensated cirrhosis, targeting a serum albumin level ≥35 g/L. Regardless of treatment assignment, patients were administered albumin infusions as clinically indicated for large-volume paracentesis, spontaneous bacterial peritonitis, and HRS. The primary outcome was a composite of infection from any cause, kidney dysfunction, or death. This definition was amended during the trial (organ dysfunction was changed to kidney dysfunction only), but no benefit of targeted albumin infusions was seen for the composite outcome. Although equating levels of renal dysfunction with infection and death seems disproportionate, these are all common complications of decompensated cirrhosis. No treatment differences were seen for any of the end point components. The albumin and standard care groups did not differ for the secondary end points of death at 28 days, 3 months, and 6 months. Patients in the albumin group received a median dose of albumin 10-fold higher than those in the standard care group, and they had more pulmonary edema and volume overload complications.

Although the results of ATTIRE should not discourage clinicians from using albumin for recognized indications, they do not support its targeted use to maintain an arbitrary serum albumin level. Studies of critically ill patients with sepsis have shown that targeted albumin infusions to maintain serum thresholds do not affect mortality. We need alternative strategies to monitor and treat the inflammatory response in decompensated cirrhosis.