Albumin reduces complications and improves survival in people with decompensated cirrhosis

Long-term administration of human albumin was associated with fewer serious complications, less hospitalisation, better quality of life and longer survival for people with decompensated liver cirrhosis, according to a report at the International Liver Congress last month in Amsterdam. The congress is the annual meeting of the European Association for the Study of the Liver (EASL).

Over years or decades, chronic hepatitis B or C, excessive alcohol consumption and other causes of liver damage can lead to advanced cirrhosis, liver cancer, and ultimately liver failure, transplantation or death.

Decompensated liver disease occurs when the liver can no longer carry out its vital functions due to the accumulation of scar tissue and blockage of blood flow. Complications include ascites (fluid build-up in the abdominal cavity), bleeding veins in the oesophagus and hepatic encephalopathy. Ascites is generally treated with diuretics and paracentesis – a procedure that involves draining fluid with a needle – but a liver transplant is the only curative therapy.

Mauro Bernardi of the University of Bologna and colleagues conducted a randomised clinical trial to assess whether long-term administration of human albumin – a protein that helps maintain fluid balance in the body – had advantages over the standard of care.

The ANSWER study enrolled 440 people with advanced cirrhosis and uncomplicated ascites at more than 30 centres in Italy. A majority were men, with an average age of 60 years.

The mean Child-Pugh score was 8.1 (Class B) and the mean MELD score – used to prioritise patients for liver transplantation – was approximately 13. Participants had been treated for ascites using diuretics (at least 25mg/day furosemide and 200mg/day anti-mineralocorticoid drugs), but those with refractory ascites who needed paracentesis twice or more in the past month were excluded, as were those with gastrointestinal bleeding, hepatocellular carcinoma and several other complications.

Participants were randomly assigned to receive either standard medical treatment using diuretics or standard treatment plus human albumin. Those in the albumin arm started with 40 grams twice weekly for two weeks, then reduced their dose to once weekly.

The primary study endpoint was overall survival, with secondary measures including need for paracentesis, other complications of cirrhosis, hospital admissions and quality of life. Study participants were followed for up to 18 months.

Fewer than half the participants completed follow-up. Major reasons for discontinuation included liver transplantation, having a transjugular intrahepatic portosystemic shunt (TIPS) procedure and, most often, needing paracentesis more than three times a month. This was the case for 18 people in the albumin arm and 42 in the standard-of-care arm.

People who received albumin had a higher survival rate than those who did not. At 18 months, 78% of people who used albumin were still alive, compared to 66% of those treated with standard therapy alone – a 38% reduction.

Participants in the albumin arm of the study were less likely to require paracentesis, and those who did needed it later and had less fluid removed. By 18 months, 38% of people in the albumin arm underwent paracentesis at least once, compared to 66% in the standard-of-care arm – a 54% reduction. Refractory ascites was seen in 25% and 48%, respectively, a 46% reduction. Both differences were highly significant.

People in the albumin arm were less likely to develop a variety of cirrhosis complications including bacterial infections, hepatic encephalopathy, bleeding varices, kidney dysfunction and hepatorenal syndrome.

In addition, people receiving albumin were hospitalised significantly less that those in the standard-of-care arm, both in terms of number of hospitalisations (35% less) and cumulative number of days in hospital (45% less).

Finally, people who received albumin reported that their quality of life improved, while those in the standard-of-care arm were more likely to say their quality of life was the same or worse at 3, 6 and 12 months.

Albumin was generally safe and well tolerated. Two participants had mild allergic reactions and two developed severe sepsis, but all four recovered.

“There has been a lack of scientific evidence proving that long-term human albumin can treat cirrhosis with ascites," Dr Bernardi said in an EASL press release. "The ANSWER study has now clarified this issue, showing that human albumin extends survival and helps better manage ascites, as well as reducing the incidence of severe complications of this very serious disease."

"Based on this data, weekly administration of albumin should be considered in patients with cirrhosis and ascites to prevent life-threatening complications," added Annalisa Berzigotti from the University of Berne.