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Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy



High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy.


This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020. Baseline information was compared between patients with low and high HBV DNA levels. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncologic outcomes.


The 217 patients included in the analysis had a median survival time of 20.6 months. Of these HBV-associated HCC patients, 165 had known baseline HBV DNA levels. Baseline HBV DNA level was not significantly associated with OS (P = 0.59) or PFS (P = 0.098). Compared to patients who did not receive antiviral therapy, patients who received antiviral therapy had significantly better OS (20.6 vs 11.1 months, P = 0.020), regardless of HBV DNA levels. Moreover, antiviral status (adjusted HR = 0.24, 95% CI 0.094–0.63, P = 0.004) was an independent protective factor for OS in a multivariate analysis of patients with HBV-related HCC.


HBV viral load does not compromise the clinical outcome of patients with HBV-related HCC treated with anti-PD-1-based immunotherapy. The use of antiviral therapy significantly improves survival time of HBV-related HCC patients.

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Fig. 1
Fig. 2

Data availability

The raw data supporting the conclusions of this article will be made available by the authors upon request.



American Association for the Study of Liver Diseases




Alanine aminotransferase


Barcelona Clinic Liver Cancer


Confidence interval


Complete response


Disease control rate


Eastern Cooperative Oncology Group Performance Status


Hepatitis B virus


Hepatitis B e antigen


Hepatitis B surface antigen


Hepatocellular carcinoma


Overall survival


Polymerase chain reaction


Progressive disease


Programmed cell death protein 1


Progression-free survival


Partial response


Response Evaluation Criteria in Solid Tumors


Stable disease


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We thank participants and participating clinicians at each study site. Thanks to Dr. Yuqing Liu for her help in managing patients, and Dr. Jiangong Zhang for assisting in analyzing the data in this paper. Many thanks to Dr. Hongle Li for the overall design of this paper. This work was supported by the National Natural Science Foundation of China (Grant No. 81972690) and Medical Science and Technology Research Project of Health Commission of Henan Province (YXKC2021007).


This work was supported by the National Natural Science Foundation of China (Grant No. 81972690) and Medical Science and Technology Research Project of Health Commission of Henan Province (YXKC2021007). The funding bodies played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.

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All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript and take responsibility for the integrity of the work as a whole. MA performed experiments, analyzed data, and wrote the manuscript. WW and JZ edited the manuscript and were responsible for revisions. BT, LZ, YY, YW, TL, and MZ were responsible for patient management. HH, HC, PQ, XZ, and LH analyzed data. ZW and QG designed and supervised the study. All authors interpreted the data and were involved in the development, review, and approval of the manuscript.

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Correspondence to Quanli Gao or Zibing Wang.

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The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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This study was approved by the ethics committees of the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China. Due to the retrospective nature of the study and because no patient specimens were used, the requirement for informed consent was waived by the ethics committees.

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An, M., Wang, W., Zhang, J. et al. Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy. Cancer Immunol Immunother 72, 385–395 (2023).

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  • Hepatocellular carcinoma
  • Immunotherapy
  • Programmed cell death protein-1
  • Hepatitis B virus