HEPATIC-INJURY DURING KETOCONAZOLE THERAPY IN PATIENTS WITH ONYCHOMYCOSIS - A CONTROLLED COHORT STUDY

To evaluate the incidence, severity, and course of ketoconazole-associ ated hepatic injury, 211 patients with onychomycosis were randomized b y a ratio of 2:1 to receive either ketoconazole (137 patients) or gris eofulvin (74 patients), All of them were seronegative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C virus (HCV) and had no bi ochemical abnormality before therapy. The two groups were comparable i n age, sex, and pretherapy liver biochemical tests, Liver biochemical tests were followed up biweekly for 3 months, and then at monthly inte rvals during the remaining course of therapy, No biochemical abnormali ty or hepatic injury was found in patients during griseofulvin treatme nt, Of the patients treated with ketoconazole, 24 (17.5%; 95% confiden ce interval [CI], 11.1% to 23.9%) showed asymptomatic transaminase ele vation. Ketoconazole was discontinued immediately after overt hepatiti s developed in another 4 patients (2.9%; 95% CI, 0.1% to 5.7%) who did not succumb to hepatic decompensation. The abnormal biochemical chang es in patients with overt hepatitis returned to normal after discontin uing ketoconazole. Elderly patients were more prone to develop overt h epatitis, Ln patients with asymptomatic liver injury, the abnormal bio chemical changes gradually returned to normal despite continuing ketoc onazole therapy, The results of this cohort study suggest that ketocon azole-induced overt hepatitis is more common than previously believed and that transient subclinical injury is much more common than overt h epatitis. Therapy with ketoconazole may be continued with caution in t he absence of symptoms and/or hyperbilirubinemia, but should be discon tinued if overt hepatitis occurs.