Delayed-onset drug-induced liver injury in a cystic fibrosis patient on long-term elexacaftor/ivacaftor/tezacaftor therapy: A case report and literature review

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) is a cystic fibrosis transmembrane conductance regulator (CFTR) modulator widely used in patients with cystic fibrosis (CF), typically associated with mild, early onset liver enzyme elevations. Methods: We report a case of a 35-year-old man with CF who developed a marked hepatic transaminitis, with an alanine aminotransferase peaking at >1,000 IU/L after 30 months of stable ETI therapy. The patient was asymptomatic, and an extensive workup excluded viral, autoimmune, and metabolic liver disease. Various imaging modalities excluded other secondary causes, such as portal venous or arterial thromboses. Results: Using the Roussel Uclaf Causality Assessment Method (RUCAM), a score of 8 indicated a probable link to drug-induced liver injury (DILI), which was further supported by World Health Organization–Uppsala Monitoring Centre (WHO–UMC) causality assessment. Conclusions: This case highlights the potential for delayed-onset hepatotoxicity with ETI and emphasizes the need for continued liver monitoring during long-term therapy.