Lapatinib-induced liver injury characterized by class II HLA and Gilbert's syndrome genotypes

Clin Pharmacol Ther. 2012 Apr;91(4):647-52. doi: 10.1038/clpt.2011.277. Epub 2012 Feb 22.


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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Alanine Transaminase / biosynthesis
  • Alanine Transaminase / genetics
  • Chemical and Drug Induced Liver Injury / epidemiology
  • Chemical and Drug Induced Liver Injury / genetics*
  • Chemical and Drug Induced Liver Injury / immunology
  • Genotype
  • Gilbert Disease / drug therapy
  • Gilbert Disease / genetics*
  • Gilbert Disease / immunology
  • Glucuronosyltransferase / biosynthesis
  • Glucuronosyltransferase / genetics*
  • HLA-DQ alpha-Chains / biosynthesis
  • HLA-DQ alpha-Chains / genetics*
  • HLA-DRB1 Chains / biosynthesis
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Incidence
  • Lapatinib
  • Quinazolines / adverse effects*


  • HLA-DQ alpha-Chains
  • HLA-DQA1 antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*07:01:01 antigen
  • Quinazolines
  • Lapatinib
  • UGT1A1 enzyme
  • Glucuronosyltransferase
  • Alanine Transaminase