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. 2023 Feb;72(2):385-395. doi: 10.1007/s00262-022-03254-w. Epub 2022 Jul 30.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Hepatitis B virus; Hepatocellular carcinoma; Immunotherapy; Programmed cell death protein-1.

MeSH terms

  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / virology
  • DNA, Viral
  • Hepatitis B, Chronic* / complications
  • Hepatitis B, Chronic* / drug therapy
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / virology
  • Neoplasm Recurrence, Local / drug therapy
  • Retrospective Studies

Substances

  • Antiviral Agents
  • DNA, Viral
  • Immune Checkpoint Inhibitors