title: Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes.
abstract: 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.
authors.affiliation: Genetics Department, GlaxoSmithKline Research & Development, Stevenage, UK. colin.f.spraggs@gsk.com
authors.forename: C F
authors.initials: CF
authors.lastname: Spraggs
authors.forename: L R
authors.initials: LR
authors.lastname: Parham
authors.forename: C M
authors.initials: CM
authors.lastname: Hunt
authors.forename: C T
authors.initials: CT
authors.lastname: Dollery
mesh_terms: D000410:Alanine Transaminase / Q000096:biosynthesis / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005838:Genotype; D005878:Gilbert Disease / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics*; D059848:HLA-DQ alpha-Chains / Q000096:biosynthesis / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D015994:Incidence; D000077341:Lapatinib; D011799:Quinazolines / Q000009:adverse effects*; D000099148:UGT1A1 Enzyme
chemical_list: D000410:Alanine Transaminase; D014453:Glucuronosyltransferase; D059848:HLA-DQ alpha-Chains; D059811:HLA-DRB1 Chains; D000077341:Lapatinib; D011799:Quinazolines; D000099148:UGT1A1 Enzyme; C069050:HLA-DQA1 antigen; C527714:HLA-DRB1*07:01:01 antigen