Fulminant hepatic failure caused by ecarazine hydrochloride (a hydralazine derivative)

Abstract

The cause of fulminant hepatic failure is reported to icant number of cases of this disease are caused by be unknown in more than half the cases in Japan. We suicide attempts with paracetamol. 3,4 In France, it is recently reviewed 23 cases of fulminant hepatic failure often caused by ingestion of poisonous mushrooms. 5,6 that had been treated at our hospital. The cause of dis-According to a nationwide survey of fulminant hepatic ease had been regarded as unknown before this study. failure among Japanese in 1993, the cause was attribIt was found that seven of these patients had been under uted to acute hepatitis A in 16% of all cases, acute ecarazine hydrochloride therapy when they developed hepatitis B in 22%, drug-induced hepatitis in 10%, and fulminant hepatic failure. We examined the reasons why was unexplained in 52%.2 Identification of the cause of fulminant hepatic failure in these seven patients had not unexplained fulminant hepatic failure, which accounts been previously attributed to ecarazine, and found that for more than half of all cases, is essential in selecting it could be explained by the following factors: (1) the time from the start of ecarazine therapy to the onset of optimal therapies and preventing the onset of this dishepatic failure was long; (2) in all cases, hepatic failure ease.developed more than 10 days after the clinical recogni-In the current study, we attempted to identify the tion of hepatitis; and (3) characteristic signs of drug-cause of fulminant hepatic failure, with emphasis on induced hepatic failure such as skin rash and positive the analysis of possible relationships to drug usage, in lymphocytes stimulation test with the drug were absent 23 cases of fulminant hepatic failure of unknown cause. in all cases. Fulminant hepatic failure in these cases could be characterized by: (1) rapid decrease in serum PATIENTS AND METHODS alanine transaminase (ALT) level after discontinuationBetween 1968 and 1994, 114 patients with fulminant heof ecarazine, (2) prolonged jaundice despite discontinuapatic failure were treated at our hospital or its related facilition of ecarazine, (3) high incidence of anti-nuclear antities. Of these cases, 8 were diagnosed as caused by hepatitis body (ANA) (57%), and (4) histological findings of exten-A virus because of immunoglobulin M anti-HA, 37 were diagsive hepatocellular necrosis ranging from bridging nosed as being due to hepatitis B virus because of the presnecrosis to massive necrosis. Of the seven patients, four ence of immunoglobulin M anti-HBc, and 37 were diagnosed died of fulminant hepatic failure. These four patients as being due to drugs because of a history of using drugs had received high doses of ecarazine hydrochloride for (e.g., halothane) that were known to provoke fulminant hepaprolonged periods. Our data suggest that there may be titis and because of positive lymphocytes stimulation test many cases in which the cause of fulminant hepatic failwith the drug. The lymphocyte stimulation test with drug ure or acute hepatitis was not pre...