Comparison of cyanamide and disulfiram in effects on liver function.

Background: Cyanamide, an aversive drug widely used in Japan, develops ground-glass inclusion bodies in the hepatocytes at high incidences, which may be associated with portal inflammation and fibrosis. When cyanamide-treated alcoholics relapse drinking, the combined effect of cyanamide and alcohol produce more severe portal inflammation along with the emergence of ground-glass inclusions. Disulfiram also causes hepatitis, but there have been no comparative studies of effects of cyanamide and disulfiram on liver function.
Methods: We reviewed the laboratory data of 408 alcoholics admitted for a 3 month course of alcohol detoxification and rehabilitation. Patients tested negative for hepatitis virus markers and were diagnosed as not having cirrhosis. Among the subjects, 222 patients received cyanamide treatment (a daily dose of 70 mg) without a history of disulfiram treatment, and 186 received disulfiram (a daily dose of 200 mg) without a history of cyanamide treatment. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels obtained at 0, 4, 8, and 12 weeks of administration of each aversive drug were compared between the two alcoholic groups.
Results: Elevation of serum transaminases (AST > ALT) probably due to alcoholic liver disease quickly fell after abstinence. In patients who took cyanamide, the ALT levels were significantly higher at 4 and 12 weeks than in those who took disulfiram. Re-elevations of ALT after alcohol detoxification were more frequently observed in those who took cyanamide than in those who took disulfiram (19.4% vs. 5.9%, p < 0.001). The re-elevations of ALT were slight to moderate, being more than 3-fold in three (1.4%) patients who took cyanamide and four (2.2%) who took disulfiram. The re-elevations occurred more frequently in those with a history of cyanamide treatment before the present treatment than in those who took cyanamide for the first time (31.1% vs. 16.4%, p < 0.05).
Conclusions: Cyanamide, compared with disulfiram, was more frequently associated with elevations of ALT that persisted after abstinence.