Acute liver failure associated with prolonged use of bromfenac leading to liver transplantation

Bromfenac, a nonnarcotic analgesic nonsteroidal anti-inflammatory drug, was associated with reversible, minor elevations in serum aminotransferase lev els during clinical trials, The aim of this study is to describe the clinic al, laboratory, and histological features of 4 patients with severe bromfen ac hepatotoxicity identified at 3 tertiary care centers participating in th e US Acute Liver Failure Study Group, Bromfenac was administered for chroni c musculoskeletal disorders to 4 women in therapeutic doses of 25 to 100 mg /d for a minimum of 90 days, All patients reported a prodrome of malaise an d fatigue and presented with severe, symptomatic hepatocellular injury with associated hypoprothrombinemia, None of the subjects had underlying liver or kidney disease, and there was no evidence of a hypersensitivity reaction , Other identifiable causes of acute liver failure were uniformly excluded. Despite supportive measures, all the subjects developed progressive liver failure over 5 to 37 days, leading to emergency liver transplantation in 3 patients and death in 1 patient while awaiting transplantation, Extensive c onfluent parenchymal necrosis that appeared to begin in the central zones a nd was accompanied by a predominantly lymphocytic infiltrate was noted in a ll the livers examined. Nodular regeneration was seen in the 2 patients wit h a move protracted clinical course. Administration of therapeutic doses of bromfenac for greater than 90 days was associated with the development of acute liver failure leading to liver transplantation or death in 4 adult wo men. The poor outcomes observed in this series, coupled with the inability to identify individuals at risk for severe, idiosyncratic bromfenac hepatot oxicity, preclude further use of bromfenac in the medical community. Copyri ght (C) 1999 by the American Association for the Study of Liver Diseases.