DRUG-INDUCED HEPATIC INJURY

A review of the japanese articles for the past 70 years

Abstract

Drug-induced hepatic injury is one of the important problems in medical practice in recent years in Japan.
We collected 8156 cases of drug-induced hepatic injury reported in Japanese articles published over a period of 70 years from 1911 to 1980.
The greatest number of cases of drug-induced hepatic injury was due to antibiotics 2729, followed by drugs acting on the central nervous system 1223, chemotherapeutic drugs 1174, cardiovascular drugs 879, carcinostatic agents 604, hormones and hormone antagonists 452, diagnostic aids 370, and other drugs 725.
Ten of the most common drugs which caused hepatic injury were chephalosporins, penicillins, thorium dioxide, arsphenamine, aminoglycosides, ethionamide, refampicine, macrolides, 4, 4'-diethylaminoethoxy hexestrol, cholrpromazine in descending order of frequency.
The common clinical symptoms were gastrointestinal complaints, jaundice, fever, hepatomegaly and less frequently skin eruption.
Approximately 93% of all cases were diagnosed on the basis of clinical history and laboratory tests. Readministration test, skin test, lymphocyte stimulation test and macrophage migration inhibitory test of suspected drugs were also performed as a diagnostic aid in nearly 7% of all cases. The positive rate of macrophage migration inhibitory test was 92.62%, that of readministration test 92.33%, lymphocyte stimulation test 88.83% and skin test 66.52%.
The total 8156 cases included 395 fatal cases. The highest fatality rate was shown by thorium dioxide (153 cases), followed by halothane (28 cases), pyrazinamide (22 cases), arsphenamine (21 cases), 4, 4'-diethylaminoethoxy hexestrol (20 cases) in descending order.