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, 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 attrib-It 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 drugcause 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 discontinuation
Between 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 previously determined was performed according to the method of Mizoguchi et al. 7 that can be attributed to long-term drug therapy for
The remaining 49 were regarded as fulminant hepatic failure chronic diseases. (HEPATOLOGY 1996;23:465-470.) of unknown cause. Of these 49 cases, adequate records were available for 23 cases (7 men and 16 women), and patient
In Western countries, active intervention such as ages ranged from 22 to 81 years (mean, 48.0 { 17.4 years). liver transplantation has been performed for the treat-Sixteen (70%) of these 23 patients had been receiving drug ment of fulminant hepatic failure. Despite such efforts, therapy before the onset of hepatic failure. Of these 16 pa- however, the prognosis of this disease is very poor. In tients with a history of drug therapy, 7 had received ecarazine Japan, the survival rate of patients with this condition hydrochloride (a hydralazine derivative) to treat hyperten- sion. We describe clinical features of 7 patients who devel-is very low (26%). 2 Causes of fulminant hepatic failure oped fulminant hepatic failure caused by ecarazine hydrovary among countries. In the United Kingdom, a signifchloride.
Sera taken before administration of blood preparations and stored at 020ะC were available in six cases. These sera were Abbreviations: HCV, hepatitis C virus; ANA, antinuclear antibody; AST, checked for hepatitis C virus (HCV) RNA, using the reverseaspartate transaminase; ALT, alanine transaminase.