Clinical Features of Voriconazole-induced Hepatotoxicity in Pediatric Patients

Abstract

Hepatotoxicity associated with the administration of voriconazole (VRCZ) is a treatment-related adverse event that necessitates discontinuation of administration in some cases. This study is aimed at investigating the clinical features of VRCZ-induced hepatotoxicity in pediatric patients, including the status of hepatic damage before the administration of VRCZ.

Demographic and laboratory data were retrieved retrospectively from the medical records of 13 Japanese pediatric patients who underwent VRCZ therapy. Based on this study and other studies, we examined the relationship between the ratio of patients with hematologic malignancy / solid tumors to the underlying disease and the occurrence of VRCZ-induced hepatotoxicity.

There have been 10 cases (76.9％) with hepatic damage before the administration of VRCZ. VRCZ-induced hepatotoxicity was observed in 11 cases (84.6％), 7 cases (63.6％) of which were severe. The median values of time to the occurrence of VRCZ-induced hepatotoxicity and time to becoming severe were 5 and 7 days respectively after the first dose of VRCZ. As the ratio of patients with hematologic malignancy / solid tumors to the underlying disease increased, the occurrence of VRCZ-induced hepatotoxicity tended to increase (P < 0.01). Of the liver function tests, an abnormal increase in aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase occurred with high probability in patients diagnosed as having VRCZ-induced hepatotoxicity.

These results suggest that VRCZ-induced hepatotoxicity may occur with high probability early after initiating the administration of VRCZ in pediatric patients. We therefore recommend frequent liver function tests in pediatric patients treated with VRCZ, at least around the first 5 days.