TOPLINE:

In patients with chronic liver disease (CLD) treated with systemic antifungals for moderate-to-severe onychomycosis, terbinafine was associated with the lowest risk for drug-induced liver injury, whereas voriconazole was associated with the highest risk.

METHODOLOGY:

• Researchers queried the TriNetX research network from 2005 to 2025 for patients with CLD who received systemic antifungals for onychomycosis.
• Treatment courses were defined within 180-day prescription windows; drug-induced liver injury (classified as hepatocellular, cholestatic, or mixed) was assessed from liver-function tests.
• Researchers performed propensity score matching on demographics and baseline liver function tests to compare terbinafine (n = 1317), ketoconazole (n = 36), voriconazole (n = 147), posaconazole (n = 102), and itraconazole (n = 105) with fluconazole (n = 2018). Fluconazole served as the reference treatment.

TAKEAWAY:

• After propensity score matching, terbinafine was associated with a lower risk for drug-induced liver injury than fluconazole (2.81% vs 5.24%; relative risk [RR], 0.54; P = .0021).
• Voriconazole was associated with a higher risk for liver injury than fluconazole (23.13% vs 6.12%; RR, 3.78; P = .0001), whereas itraconazole was associated with the same incidence as fluconazole (4.76% for both).
• Posaconazole (8.82% vs 3.92%; RR, 2.25; P = .25) and ketoconazole (11.11% vs 3.2%; RR, 4.00; P = .35) risks for hepatotoxicity were not significantly different compared with fluconazole. (The authors of the study noted that small sample sizes limited interpretation of these associations and that ketoconazole is the most hepatotoxic azole.)

IN PRACTICE:

“Terbinafine remains the preferred agent for moderate-to-severe onychomycosis with CLD given its favorable hepatotoxicity profile,” the authors of the study concluded. “Emerging resistance may necessitate alternative agents, underscoring the importance of understanding relative hepatotoxicity across agents,” they added, noting that prospective studies are needed to “validate these findings and optimize clinical decision-making.”

SOURCE:

The study was led by Rebecca Zhang, Weill Cornell Medical College, New York City, and was published online on March 31, 2026, in the Journal of the American Academy of Dermatology.

LIMITATIONS:

The study was retrospective and was subject to possible misclassification of diagnoses, prescriptions, and laboratory values. Concomitant medications, comorbidities, alcohol use, and other confounders were not controlled for, and patients receiving voriconazole or posaconazole likely represented higher-acuity or refractory cases, creating possible confounding by indication.

DISCLOSURES:

The study did not receive any specific funding. One author declared serving as a consultant for BelleTorus Corporation and Moberg Pharma AB. The remaining authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.