Clinical

Study IDs hepatotoxic drugs that most often lead to liver transplantation

Last Updated: 2009-07-15 17:50:18 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Acetaminophen, antituberculosis drugs, antiepileptics, and antibiotics are the top four drug groups causing drug-induced acute liver failure leading to liver transplantation, according to data from the United Network for Organ Sharing (UNOS).

In the July issue of Liver Transplantation, Dr. Ayse L. Mindikoglu from the University of Maryland School of Medicine, Baltimore, and colleagues report that 661 patients underwent liver transplantation for drug-induced acute liver failure in the US between October 1987 and December 2006.

Acetaminophen was implicated in 265 cases (40%), antituberculosis drugs in 50 (8%), antiepileptics in 46 (7%), and antibiotics in 39 (6%).

Actuarial patient survival at one year after transplant was 76% for acetaminophen-related acute liver failure, 82% for antituberculosis drugs, 52% for antiepileptics, 82% for antibiotics, and 79% for other drugs.

The markedly lower rate of survival after liver transplantation for antiepileptic drug-induced acute liver failure was seen mostly in children, the authors note. Of the 22 patients younger than age 18 with drug-induced acute liver failure caused by antiepileptics, 73% died within the first year.

"The identification of poorer outcome for children with antiepileptic drug-induced acute liver failure is intriguing and points out the need for more focused research on drug-induced liver injury in pediatric populations," Drs. Paul H. Hayashi and Paul Watkins of University of North Carolina, Chapel Hill, comment in a related editorial.

There was no statistically significant difference in overall survival between acetaminophen-related and non-acetaminophen-related acute liver failure.

The rate of pretransplant dialysis was highest among recipients with acetaminophen-induced acute liver failure (27%), which is "not surprising," Dr. Mindikoglu and colleagues point out, "given that renal failure occurs in a high percentage of patients who have acetaminophen-induced acute liver failure."

Pretransplant need for life support, an elevated creatinine level, and drug-induced acute liver failure due to antiepileptic drugs before age 18 were strong independent predictors of posttransplant death.

"Overall," Drs. Hayashi and Watkins say, Dr. Mindikoglu's team "must be commended for adding valuable information regarding drug-induced acute liver failure."

The editorialists conclude: "Drug-induced liver injury, though rare, has wide implications for all of us who take and prescribe medications."

Liver Transpl 2009;15:675-676,719-729.