SAN FRANCISCO – Outcomes after liver transplantation for acute liver failure steadily improved during a recent period spanning about 2 decades, researchers reported at the annual meeting of the American Association for the Study of Liver Diseases.

An analysis of data from nearly 5,000 European patients found that rates of both graft survival and patient survival increased over time, even as the mean age of donors and recipients was rising.

However, rates of graft loss and death remained high during the first year after surgery, driven mainly by infection, rejection, and primary delayed function or nonfunction of the graft.

"A progressive and constant improvement in the survival rate after liver transplantation for acute liver failure has been achieved in the last 20 years despite an increase in donor and recipient age," commented lead investigator Dr. Giacomo Germani. "High mortality and graft loss still persist, especially within the first year posttransplant."

Importantly, deaths and graft losses due to social causes – mainly nonadherence to therapy and suicide – were much more common among patients who underwent transplantation because of paracetamol (known as acetaminophen in the United States) toxicity than among other patients. And more than half of these events occurred in the first year, suggesting that early psychiatric and related intervention for this group of recipients could be beneficial, according to Dr. Germani.

For the study, the investigators analyzed data from the European Liver Transplant Registry, which captures data on liver transplants done in 23 countries. The authors identified 4,903 patients older than 16 years who underwent isolated liver transplantation for fulminant or subfulminant acute liver failure between 1988 and 2009.

Temporal trends showed that the annual number of transplantations for acute liver failure increased until approximately 1994 and then remained essentially stable thereafter, reported Dr. Germani, who is a research fellow with the Royal Free Hospital and University College London, and a physician with the Padova (Italy) University Hospital.

On average, recipients were 39 years old and donors were 41 years old, but the age of both groups increased during the study period.

"The most important change [over time] was the increase in the donor age," Dr. Germani maintained. For example, donors older than 60 years made up merely 2% of all donors in 1988-1993 but 21% in 2004-2009.

There was a shift in the etiology of the acute liver failure leading to transplantation during the study period that most likely reflected more effective diagnosis, he said. The proportion of cases recorded as having an unknown etiology fell from 60% in 1988-1993 to just 33% in 2004-2009. Meanwhile, there were increases in the proportions attributed to paracetamol toxicity, other drug toxicity, and other known causes (for example, traumatic or operative liver injury).

For the entire study period, the cumulative 10-year rates of graft and patient survival were 50% and 63%, respectively, "almost comparable with [those for] transplantation for other etiology," Dr. Germani observed.

Both outcomes improved significantly during the study period. For example, the cumulative 5-year rate of graft survival improved steadily from about 50% in 1988-1993 to about 70% in 2004-2009 (P less than .001).

Social causes accounted for just 1% of all deaths and graft losses for the entire cohort. But they accounted for nearly 8% of those among patients who underwent transplantation because of paracetamol toxicity.

Temporal trends in the causes of death or graft loss showed increases in the proportions that were due to cardiovascular causes (likely related to increasing recipient age) and to primary delayed function or nonfunction of the graft (likely related to increasing use of livers from donors having less favorable characteristics), according to Dr. Germani.

After determining that mortality and graft loss were most common in the first year after transplantation and particularly in the first 3 months, the investigators identified independent risk factors for these outcomes and incorporated them into predictive models.

There was generally good correspondence between observed and model-predicted mortality and graft loss, according to Dr. Germani.

When applied to older adults, the models identified those at especially high risk for poor outcome. For example, among the cohort of patients older than 50 years of age, the risk of graft loss or death in the first year after transplantation was 44% to 61% if the patient was older than 60 years, was male, or had an incompatible ABO match with the donor, depending on the factor. With all three factors combined, the risk jumped to 80%.

"It is therefore important to reevaluate the selection of older patients with acute liver failure as potential recipients for liver transplantation in order to avoid futile transplants," Dr. Germani recommended.

Dr. Germani reported that he had no relevant conflicts of interest.

Transplant Outcomes for Acute Liver Failure Improve Steadily