Nilotinib-induced liver injury: A case report

Area of Science:

• Oncology
• Pharmacology
• Hepatology

Background:

• Nilotinib is a BCR-ABL tyrosine kinase inhibitor used for chronic myelogenous leukemia (CML).
• High-dose nilotinib is associated with elevated serum bilirubin, necessitating dose adjustments or treatment cessation.
• The link between nilotinib-induced hyperbilirubinemia and actual liver damage remains unclear.

Observation:

• A CML patient developed hyperbilirubinemia during nilotinib therapy.
• Dose reduction temporarily resolved hyperbilirubinemia but impaired hematological response.
• Liver histology showed no significant damage, and a UGT1A1 mutation was identified.

Findings:

• Hyperbilirubinemia was confirmed as an adverse drug reaction (ADR) to nilotinib, not drug-induced liver injury.
• The pathogenic mechanism may involve inhibition of uridine diphosphate-glucuronosyltransferase (UGT1A1) activity.
• A UGT1A1 mutation (ex1 c.686C>A) was detected in the patient and his mother.

Implications:

• Reducing nilotinib dosage alleviates hyperbilirubinemia but compromises major molecular response (MMR).
• Continuing nilotinib therapy without dose adjustment may be more beneficial for CML management.
• Further research is needed to balance CML treatment efficacy and nilotinib-induced hyperbilirubinemia.