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HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity: a systematic review and meta-analysis

The Pharmacogenomics Journal volume 20, pages 47–56 (2020)Cite this article

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Abstract

Associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity have been reported. To consolidate the results from all available reports in scientific databases, systematic review and meta-analysis techniques were used to quantify these associations. Studies investigating associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity were systematically searched in PubMed, Human Genome Epidemiology Network, and the Cochrane Library. Primary outcomes were the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. Overall odds ratios (ORs) with the corresponding 95%CIs were calculated using a random-effect model to determine the associations between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity. A clear association between HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity was identified in our analyses. The summary OR was 6.23 (95%CI = 4.11–9.45). Similar associations were also found in the subgroup analyses by lapatinib treatment regimens. ORs were 10.04 (95%CI = 6.15–16.39), 8.65 (95%CI = 4.52–16.58), and 3.88 (95%CI = 2.20–6.82) in the lapatinib group, lapatinib + trastuzumab group, and lapatinib + chemotherapy or lapatinib + trastuzumab + chemotherapy group, respectively. Since HLA-DRB1*07:01 is associated with lapatinib-induced hepatotoxicity, genetic screening of HLA-DRB1*07:01 in breast cancer patients prior to lapatinib therapy is warranted for patient safety. In addition, further studies should define the risk of HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity in specific ethnicities.

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Acknowledgements

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand

    Wimonchat Tangamornsuksan

  2. Center of Excellence for Environmental Health & Toxicology, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Chuenjid Kongkaew, C. N. Scholfield & Manupat Lohitnavy

  3. Centre for Safety and Quality in Health, Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Chuenjid Kongkaew

  4. Pharmacokinetic Research Unit, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Chuenjid Kongkaew & Manupat Lohitnavy

  5. Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand

    Chuenjid Kongkaew, C. N. Scholfield & Manupat Lohitnavy

  6. Clinical Pharmacy Division, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand

    Suphat Subongkot

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Contributions

All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Statistical analysis: Dr Tangamornsuksan. Study supervision: Dr Lohitnavy. Study concept and design: Dr Tangamornsuksan, Dr Kongkaew and Dr Lohitnavy. Acquisition, analysis, and interpretation of data: Dr Tangamornsuksan, Dr Kongkaew and Dr Lohitnavy. Drafting of the manuscript: Dr Tangamornsuksan, Dr Scholfield and Dr Lohitnavy. Critical revision of the manuscript for important intellectual content: Dr Scholfield and Dr Lohitnavy.

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Correspondence to Manupat Lohitnavy.

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Tangamornsuksan, W., Kongkaew, C., Scholfield, C.N. et al. HLA-DRB1*07:01 and lapatinib-induced hepatotoxicity: a systematic review and meta-analysis. Pharmacogenomics J 20, 47–56 (2020). https://doi.org/10.1038/s41397-019-0092-2

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