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Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus

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A Correction to this article was published on 06 December 2021

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Abstract

The use of anti-programmed cell death-1 (PD-1) antibodies in treating malignancies is increasing; however, most registered clinical trials on anti-PD-1 antibodies exclude patients infected with hepatitis B virus (HBV). This retrospective study aimed to assess hepatotoxicity in cancer patients infected with HBV undergoing anti-PD1 antibody therapy and identify the associated risk factors. A total of 301 cancer patients positive for hepatitis B core antibodies (HbcAb) (negative or positive hepatitis B surface antigen [HBsAg]) who received PD-1 inhibitors were enrolled. The primary and secondary endpoints were the incidence rate of hepatotoxicity related to PD-1 inhibitor treatment, and risk factors associated with hepatic toxicity, respectively. Of the enrolled analyzed, 16.9% (n = 51) developed any grade and 4.7% (n = 14) developed grade 3–4 hepatotoxicity, respectively. Higher risk for any-grade hepatotoxicity development was associated with sero-positive HBsAg (OR = 6.30; P = 0.020), existence of liver involvement (OR = 2.10; P = 0.030), and detectable baseline HBV DNA levels (OR = 2.39; P = 0.012). Patients with prophylactic antiviral therapy decreased hazard for the incidence of grade 3–4 hepatotoxicity (OR = 0.10; P = 0.016). Our results suggested chronic (HBsAg-positive)/resolved (HBsAg-negative and HBcAb-positive) HBV-infected cancer patients are at an increased risk of hepatotoxicity following PD-1 inhibitor therapy. Cancer patients should be tested for HBsAg/HBcAb prior to the commencement of immune checkpoint inhibitor therapy. For patients with chronic/resolved HBV infection, ALT/AST and HBV DNA should be closely monitored during the whole immunotherapy period.

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Acknowledgements

We sincerely appreciate all the patients and their families who were included in this retrospective study.

Funding

This study was funded by grants 8217102281, 81972898, and 81872499 from the National Natural Science Funds of China; 16zxyc04 from the Outstanding Young Talents Program of Sun Yat-sen University Cancer Center; 2019A1515011090 from the Natural Science Foundation of Guangdong Province. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

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    Authors and Affiliations

    1. Department of Clinical Research, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Zuan Lin

    2. Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Xuanye Zhang, Li-na He, Haifeng Li, Shaodong Hong & Li Zhang

    3. Department of VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Yixin Zhou

    4. Department of Radiotherapy, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Chen Chen

    5. Department of Endoscopy, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Yuhong Wang

    6. Department of Nuclear Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China

      Tao Chen

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    1. Zuan Lin
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    Contributions

    SH and LZ conceived and designed the study. ZL, XZ and YZ collected, analyzed and interpreted the data. All authors were involved in the drafting, review, and approval of the report and the decision to submit for publication.

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    Correspondence to Shaodong Hong or Li Zhang.

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    Zuan Lin, Xuanye Zhang and Yixin Zhou have contributed equally.

    The original online version of this article was revised: following article note “Zuan Lin, Xuanye Zhang and Yixin Zhou have contributed equally” is missing.

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    Lin, Z., Zhang, X., Zhou, Y. et al. Hepatotoxicity associated with PD-1 blockade antibodies in cancer patients co-infected with hepatitis B virus. Cancer Immunol Immunother 71, 1247–1255 (2022). https://doi.org/10.1007/s00262-021-03082-4

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    • DOI: https://doi.org/10.1007/s00262-021-03082-4

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