Abstract / Summary
Background Voriconazole is the recommended first-line treatment for invasive pulmonary Aspergillosis . However, its nonlinear pharmacokinetics and marked interindividual variability increase the risk of drug-induced liver injury, particularly in older patients with multiple comorbidities. Case presentation A 76-year-old Asian man with chronic obstructive pulmonary disease, type 2 diabetes mellitus, hypertension, polycythemia, and glucocorticoid-induced adrenal insufficiency was admitted with an infective exacerbation of COPD. Sputum culture identified Aspergillus fumigatus , and oral voriconazole (200 mg twice daily) was initiated after initial itraconazole therapy.Four days after starting voriconazole, the patient developed jaundice and severe liver injury, with alanine aminotransferase of 1,370 U/L, aspartate aminotransferase of 389 U/L, gamma-glutamyl transferase of 1,514 U/L, and total bilirubin of 90.3 μmol/L. Voriconazole was discontinued immediately. Viral, autoimmune, and mechanical causes of liver injury were excluded. Despite drug withdrawal and supportive therapy, cholestatic liver injury continued to progress, with peak total bilirubin of 592 μmol/L. Because of persistent clinical deterioration, therapeutic plasma exchange was performed. During subsequent follow-up, jaundice gradually improved, and liver biochemical parameters showed an overall recovery trend. Coagulation, renal function, and neurological status remained preserved throughout hospitalization. Conclusions This case highlights early-onset severe voriconazole-induced liver injury with subsequent progressive cholestasis in an older patient with multiple comorbidities. Liver injury may continue to worsen despite prompt drug discontinuation. Careful monitoring of liver function during the first 1-2 weeks of voriconazole therapy and therapeutic drug monitoring, when available, may facilitate earlier recognition of hepatotoxicity and improve patient safety.