Managing liver dysfunction in haematology patients: Switch antifungals, or use the tincture of time?

Liver function test (LFT) abnormalities are a common occurrence in haematology patients receiving antifungal therapies. The cause of elevated LFTs is often multifactorial. Posaconazole is associated with elevated LFTs in approximately 5%-10% of patients. Recently, DiPippo, et al demonstrated that switching to isavuconazole in such cases leads to a reduction in LFTs in the majority of patients. However, the LFTs in such patients may have declined with time while continuing on posaconazole therapy. We retrospectively assessed LFT kinetics in 157 AML patients receiving posaconazole for antifungal prophylaxis and found that in 27 patients who developed grade 2 or higher CTCAE hepatotoxicity, 85% (23/27) had lower LFTs at the end of posaconazole therapy, despite continuation in the setting of hepatotoxicity, and this change from maximum LFTs was statistically significant (P < 0.0001). Thus, the development of LFT abnormalities while on posaconazole therapy may not warrant a switch to an alternative, potentially less effective antifungal, as hepatotoxicity is often multifactorial and generally resolves with time in the majority of patients.