Fulminant drug-induced hepatic failure leading to death or liver transplantation in Sweden

Objective. There are only a few data on the prevalence of drug-induced liver injury associated with fatal outcome. The aim of this study was to determine the nature and number of suspected adverse drug-induced liver disease associated with fatalities and/or liver transplantation since reporting of adverse drug reactions (ADRs) started in Sweden. Material and methods. All reports of suspected hepatic ADRs with fatal outcome received by the Swedish Adverse Drug Reactions Advisory Committee ( SADRAC) from 1966 to 2002 were reviewed and causality assessed. Results. The SADRAC received 151 reports of suspected ADRs with fatal outcome from liver injury; 48 cases were either unlikely or excluded. Of the remaining 103 cases, 13 (13%) were highly probable, 48 (47%) probable and 42 (41%) possible. The median age of the 103 patients was 64 years ( 47 - 77 interquartile range (IQR)) and 59 (57%) were males. The majority of cases were classified as hepatocellular (75%), with only 15% cholestatic and 10% mixed. Halothane, paracetamol, flucloxacillin, sulfamethoxazole/trimethoprim and diclofenac were the most common drugs associated with fatal outcome. Seventeen patients underwent liver transplantation, most commonly because of paracetamol and disulfiram toxicity. Conclusions. A wide range of suspected ADRs are associated with fatalities. Antibiotics and analgesics are associated with the greatest number of reports of deaths.