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Lapatinib‐Induced Liver Injury Characterized by Class II HLA and Gilbert's Syndrome Genotypes
Author(s) -
Spraggs C F,
Parham L R,
Hunt C M,
Dollery C T
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.277
Subject(s) - lapatinib , clinical pharmacology , human leukocyte antigen , medicine , liver injury , gilbert's syndrome , alanine aminotransferase , genotype , incidence (geometry) , pharmacology , breast cancer , gastroenterology , oncology , cancer , immunology , antigen , genetics , biology , gene , trastuzumab , physics , bilirubin , optics
Lapatinib is a clinically important component of the treatment for HER2‐positive metastatic breast cancer and has an acceptable safety profile. Lapatinib‐associated Hy's Law cases have been characterized using human leukocyte antigen ( HLA ) DQA1 *02:01/ DRB1 *07:01 and Gilbert's syndrome UGT1A1 *28/*28 genotypes. The HLA‐positive cases had higher alanine aminotransferase (ALT) elevation, whereas the HLA‐negative cases had a higher incidence of Gilbert's syndrome. The findings of our study, which extend this HLA association to lapatinib‐associated serious liver injury, emphasize the importance of Gilbert's syndrome in the interpretation of Hy's Law and may lead to methods for enhancing patient safety. Clinical Pharmacology & Therapeutics (2012); 91 4, 647–652. doi: 10.1038/clpt.2011.277