HLA Polymorphisms And TKI-Induced Liver Injury in Patients with Cancer: A Meta-analysis

Background: Tyrosine kinase inhibitors (TKIs) are widely used for patients with cancer, although liver injury has been observed in a small proportion of these patients. The aim of this study was to investigate the mechanisms underlying TKI-induced liver injury according to HLA polymorphisms. Methods: We systematically searched three electronic databases (PubMed, PMC, EmBase, and the Cochrane library) to identify studies that evaluated the impact of HLA polymorphisms on the incidence of TKI-induced liver injury in cancer patients as of November 2018. The summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Further, sensitivity analysis and publication bias assessments were also performed. Results: In the final analysis, four studies that involved a total of 12,181 patients were included. Three of the studies included patients who received lapatinib, and the other study included patients who received pazopanib. Overall, carriers of HLA-DQA1*02:01 were associated with an increased risk of liver injury (OR: 6.85; 95%CI: 2.34-20.02; P<0.001). Furthermore, HLA-DQB1*02:02 was correlated with a greater risk of liver injury (OR: 5.61; 95%CI: 2.80-11.25; P<0.001). Finally, HLA-DRB1*07:01 was significantly correlated with a greater risk of liver injury (OR: 4.06; 95%CI: 2.33-7.09; P<0.001). Conclusions: The findings of this meta-analysis confirmed that three polymorphisms of HLA were significantly associated with an increased risk of TKI-induced liver injury. Further work will be required to determine these relationships in patients with specific characteristics.