Albumin provides no benefit to hospitalised patients with advanced liver disease
Daily infusions of albumin provide no significant health benefit to patients hospitalised with advanced liver cirrhosis, over and above ‘standard care’ where patients receive substantially less albumin, according to a large trial led by UCL and UCLH published in the New England Journal of Medicine.
In the trial supported by CRN North Thames, researchers said the data suggest use of the therapy – which is expensive – should be abandoned. They called for a focus on preventing the causes of liver disease, including excessive alcohol use and obesity.
Albumin prevents fluid leaking from the bloodstream. In people with liver disease, low albumin levels are associated with an increased risk of death among hospitalised patients who have cirrhosis, and lab studies have shown albumin to have an anti-inflammatory effect. Albumin infusions have therefore been considered the best fluid for patients with cirrhosis and are an integral part of clinical care.
Principal Investigator Professor Alastair O’Brien (UCL Division of Medicine) said: “Albumin infusions have been used with great enthusiasm by liver specialists for 70 years, are widely believed to be the best at reducing abnormal fluid build-up caused by cirrhosis and preclinical studies support an anti-inflammatory role. However, albumin is considerably more expensive than other fluids, shortages in production do occur and, crucially, confirmatory large-scale clinical trials to support use are lacking.
“To establish a better evidence base, we examined whether increasing a serum albumin level of 30 g/L [grams per Litre] or greater in these patients with repeated daily infusions of human albumin solution, compared with standard UK albumin use, would reduce the incidences of infection, kidney dysfunction, and death.”
In the ATTIRE (Albumin to Prevent Infection in Chronic Liver Failure) trial, 777 patients hospitalised with acute decompensated liver cirrhosis were randomly placed in one of two groups. 380 patients were given daily infusions of human albumin solution to raise the concentration in the blood to 30 grams of albumin per litre or greater, for up to 14 days or until discharge. 397 patients were given ‘standard care’, which could include albumin infusions for draining ascites (fluid in the abdomen) or renal failure, for up to 14 days or until discharge.
The targeted albumin group received about 10 times more albumin and serum albumin levels rose to 30 grams per litre or greater within three days in this group, whereas levels remained at 25 grams per litre or lower in the standard care group.
In the targeted albumin group, 113 of 380 patients (29.7%) developed one of the primary end points: infection, renal dysfunction or death. In the standard care group it was 120 of 397 patients (30.2%). Across all hospitalised patients one third (32.3%) had died within six months of initiating treatment.
Researchers concluded there is no evidence of benefit for targeted albumin – and more severe or life-threatening serious adverse events occurred in patients in the targeted albumin group.
Professor O’Brien said: “Our large, high quality, randomised trial showed no benefit for targeted albumin infusions and those given higher doses, in fact, had more serious adverse events. These data strongly support both the need to abandon the use of this costly therapy, and a reappraisal of our understanding of this complex condition. Finally, the high mortality in these patients does not appear to have changed in 20 years. This calls for a renewed focus on preventing the major causes of liver disease, excessive alcohol consumption and obesity.”
In North Thames, patients were recruited at The Royal Free Hospital NHS Trust, Basildon and Thurrock University Hospitals NHS Foundation Trust, Barts Health NHS Trust and Whittington Health NHS Trust.