Low levels of albumin present a serious problem for people with cirrhosis, putting them at higher risk of infection, kidney disease and death.
The ATTIRE study – a research project led by scientists and clinicians at University College London – aimed to find out whether or not increasing albumin levels in patients with cirrhosis through an albumin infusion would reduce the number of cases of infection, kidney disease and death.
Professor Alastair O'Brien, who led the team, explains more about the project and what the results mean for people with liver disease.
What is albumin and what has it got to do with liver disease?
"Albumin is a protein produced by the liver that circulates in plasma (the clear liquid portion of your blood). It plays many vital roles in the human body, such as preventing fluid from leaking out of the bloodstream. Low albumin levels are an indicator of liver disease, and the protein is often included in blood tests to check liver function.
"People with cirrhosis often have lower than normal albumin levels as their liver function starts to decrease. Unfortunately, low albumin levels are associated with an increased risk of death among hospitalised patients.
"Today, albumin infusions into a vein through an intravenous drip are an integral part of clinical care for people with cirrhosis. However, there are drawbacks: albumin is considerably more expensive than other fluids; shortages in production do occur; and, crucially, we lack large-scale clinical trials to support its use."
What happened during the trial?
"In the 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 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 kidney failure, for up to 14 days or until discharge. Levels remained at 25 grams per litre or lower in this group."
What did the research find out?
"We found that daily infusions of albumin provide no significant health benefit to patients hospitalised with advanced liver cirrhosis, over and above those who had ‘standard care’.
- In the group with higher albumin levels, 113 of 380 patients (29.7%) developed an infection, kidney dysfunction or died.
- In the standard care group 120 of 397 patients (30.2%) developed an infection, kidney dysfunction or died.
- Of all hospitalised patients, sadly one third (32.3%) had died within six months of starting treatment."
What are the wider implications?
"Our large, high quality, randomised trial showed no benefit for targeted albumin infusions and those given higher doses. In fact, patients in this group actually had more serious health events, especially fluid build up in the lungs (pulmonary oedema). This data strongly supports both the need to abandon the use of this costly therapy, and a reappraisal of our understanding of this complex condition.
"Unfortunately, people with cirrhosis have a high mortality rate and this has not changed in 20 years. While more clinical research is needed into treatment of the disease, we also need a renewed focus on preventing the major causes of preventable forms of liver disease – alcohol, obesity and viral hepatitis – to avoid the need for invasive treatment in the first place."