AMSTERDAM – Long-term treatment with human albumin improved the overall survival of patients with decompensated liver cirrhosis, compared with standard medical care, in a randomized, controlled trial presented at the International Liver Congress.
The final results of the ANSWER study showed that a 38% reduction in the risk of death could be achieved at 18 months’ follow-up by giving patients human albumin, with an overall survival of 78% vs. 66% in the two groups, respectively (hazard ratio, 0.62; 95% confidence interval, 0.40-0.95; P = .028).
“Long-term albumin administration to patients with decompensated cirrhosis may be seen as a disease-modifying treatment,” said the presenting study author, Mauro Bernardi, MD, professor in the department of medical and surgical sciences at the University of Bologna (Italy).
Not only was the overall survival improved, but there was improvement in the management of ascites, a reduction in the incidence of severe complications (such as spontaneous bacterial peritonitis, renal dysfunction, and hepatic encephalopathy), a reduction in the number of hospitalizations and duration of in-hospital treatment, and a signal for improved quality of life, he said.
“We know that it is good to give albumin as an infusion in many, many circumstances,” said Frank Tacke, MD, PhD, who was not involved in the study, during a press briefing at the meeting, sponsored by the European Association for the Study of the Liver (EASL).
“What we did not know before was if there was a role for giving albumin – which is unfortunately quite expensive – for a longer period of time in patients with liver cirrhosis,” said Dr. Tacke, who is the EASL vice-secretary and professor of medicine in the department of gastroenterology, metabolic diseases and intensive care medicine at University Hospital Aachen (Germany).
Although long-term treatment with human albumin is a relatively expensive treatment, particularly because it requires weekly infusion, Dr. Bernardi noted that a cost analysis was being performed, and potentially the cost of treatment could be offset by the reduction in paracentesis, duration of hospitalization, and reduced need for treating patients with complications, compared with standard medical care alone.
“The idea of supplying albumin to patients with advanced cirrhosis is quite an old one, and there is long debate. The point is that a reliable study that could resolve this was simply lacking up to now,” Dr. Bernard said at the briefing.
The results could mean that patients with decompensated cirrhosis now have a much-needed therapeutic option. These patients have “a very poor prognosis,” Dr. Bernardi said. The 1-year probability of survival is about 20%, and the only curative therapy at present is liver transplantation.
A total of 440 patients, mostly male with an average age of 61 years, with cirrhosis and uncomplicated ascites were randomized at 33 Italian centers to receive standard medical treatment alone (n = 213) or with human albumin (n = 218) given at an infused dose of 40 g twice a week for the first 2 weeks, then 40 g every week. The albumin used in the trial was provided by five different pharmaceutical companies and sent to a central location for generic relabeling and distribution out to the participating trial centers.
Significantly fewer patients who were given human albumin than those who were not (66% vs. 38%, P less than .001) needed at least one paracentesis. The incidence rate for the removal of peritoneal fluid in the standard medical treatment arm was 3.5/person per year. There was a 54% reduction in this rate by the addition of human albumin (HR = 0.46; 95% CI, 0.40-0.53; P less than .0001). There was also a significant 46% reduction in the incidence of refractory ascites (48% vs. 25%, P less than .0001).
Patients who received standard medical treatment plus albumin needed fewer hospitalizations and fewer days of in-hospital care per person per year than those in the standard care–only arm. The use of human albumin reduced the number of hospital stays by 35% (HR = 0.65; 95% CI, 0.55-0.77; P less than .0001) and the duration of days in hospital by 45% (HR = 0.55; 95% CI, 0.52-0.58; P less than .0001).
Although not statistically significant, a trend for greater improvements and fewer decreases in quality of life, as measured using the EQ-5D visual assessment scale, at 3, 6, and 12 months, was seen with the use of human albumin.
Four patients had adverse drug reactions: two were mild allergic reactions, and two were potentially life-threatening septic shock that needed intensive care treatment. One of the latter cases might have been caused by pneumonia, and the other required study interruption. But in all cases the patients recovered, Dr. Bernardi reported.
The study was funded by the Italian Drug Agency. Dr. Bernardi had acted as a speaker for and consultant to CLS Behring and Baxter Healthcare, and as a speaker to the Plasma Protein Therapeutics Association’s Europe division, Grifols, Gilead Sciences, and AbbVie Italia. Dr. Tacke had nothing to disclose.