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Comparison of hepatitis B virus reactivation in hepatocellular carcinoma patients who received tyrosine kinase inhibitor alone or together with programmed cell death protein-1 inhibitors

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Abstract

Background and aims

Programmed cell death protein-1 (PD-1) inhibitors plus tyrosine kinase inhibitor (TKI) have dramatically improved survival of patients with advanced hepatocellular carcinoma (HCC). However, the risk of hepatitis B virus (HBV) reactivation from these antitumor medications remains unclear.

Methods

Patients receiving TKI monotherapy (TKI group) or TKI combined with PD-1 inhibitors (combination group) were included. The primary endpoint was HBV reactivation as defined by an increase in HBV DNA titer by at least 1 log (tenfold) from baseline. The secondary endpoints included tumor progression and overall survival.

Results

Four hundred and ninety-nine patients met the inclusion criteria, including 296 patients in the TKI group and 203 patients in the combination group. The 3-, 6- and 12-month cumulative incidence rates of HBV reactivation in the TKI group vs. combination group were 7.8%, 12.8% and 21.3% vs. 9.9%, 19.2% and 30.0%, respectively (p = 0.02). The Cox proportional hazard model indicated that combination therapy (HR 1.41, 95% CI 1.00–1.99, p = 0.05), ALT > 40 U/ml (HR 1.50, 95% CI 1.05–2.16, p = 0.03), and tumor size > 5 cm (HR 1.58, 95% CI 1.10–2.28, p = 0.01) were independent risk factors for HBV reactivation. Compared with the HBV reactivation group, the progression-free survival and overall survival of patients in the HBV non-reactivation group were significantly prolonged (p < 0.001 and p = 0.001).

Conclusions

Patients who received TKI combined with PD-1 inhibitors had a greater risk for HBV reactivation, and those with HBV reactivation had a higher rate of tumor progression and shorter survival time, than those receiving TKI alone.

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Data availability

All our authors promise that the data mentioned in the article are available without any conflict of interest.

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Acknowledgements

We thank the patients and their families. This work was supported by the Issued by the Science, Technology and Innovation Commission of Shenzhen Municipality (KCXFZ202002011006448).

Funding

The study was supported by Science, Technology and Innovation Commission of Shenzhen Municipality (KCXFZ202002011006448).

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Author notes

  1. Jin Lei, Tao Yan, and Linzhi Zhang contributed equally.

Authors and Affiliations

  1. Guizhou Medical University, Guiyang, China

    Jin Lei, Xiaoqiang Gao, Shi Zuo & Yinying Lu

  2. Comprehensive Liver Cancer Center, The 5th Medical Center of the PLA General Hospital, Beijing, China

    Tao Yan, Linzhi Zhang, Jiamin Cheng, Yinyin Li & Yinying Lu

  3. Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, China

    Xiaoqiang Gao & Shi Zuo

  4. Peking University 302 Clinical Medical School, Beijing, China

    Bowen Chen & Zherui Liu

  5. Guangdong Key Laboratory of Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China

    Yinying Lu

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  1. Jin Lei
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Contributions

JL and TY: study design, statistical analysis, and drafting of the manuscript. LZ, BC and JC: data interpretation and critical revision of the manuscript. XG, ZL and YL: study design, study supervision, and critical revision of the manuscript. SZand YL: study supervision, data interpretation, and critical revision of the manuscript. All the authors approved the final submission.

Corresponding authors

Correspondence to Shi Zuo or Yinying Lu.

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Conflict of interest

The Jin Lei, Tao Yan, Linzhi Zhang, Bowen Chen, Jiamin Cheng, Xiaoqiang Gao, Zherui Liu, Yinyin Li, Shi Zuo, and Yinying Lu declare no conflicts of interest that pertain to this work.

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All patients signed informed consent forms and received ethical support.

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Supplementary Fig. 1 This flowchart shows the enrollment process for patients with or without adjusted antiviral regimen (JPG 108 KB)

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Lei, J., Yan, T., Zhang, L. et al. Comparison of hepatitis B virus reactivation in hepatocellular carcinoma patients who received tyrosine kinase inhibitor alone or together with programmed cell death protein-1 inhibitors. Hepatol Int 17, 281–290 (2023). https://doi.org/10.1007/s12072-022-10450-4

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