J Cancer 2019; 10(10):2161-2168. doi:10.7150/jca.26727 This issue
1. Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing 100034, China
2. Department of General Surgery, Peking University First Hospital, No. 8, Xishikuda Street, Xicheng District, Beijing 100034, China
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.
Keywords: Tyrosine kinase inhibitors, liver injury, HLA, polymorphisms