Comparison of HBV reactivation between patients with high HBV-DNA and low HBV-DNA loads undergoing PD-1 inhibitor and concurrent antiviral prophylaxis

Cancer Immunol Immunother. 2021 Nov;70(11):3207-3216. doi: 10.1007/s00262-021-02911-w. Epub 2021 Apr 3.

Abstract

Background: Programmed cell death protein-1 (PD-1) inhibitor is recommended to treat advanced hepatocellular carcinoma (HCC). However, the safety of PD-1 inhibitor in patients with high HBV-DNA load is unknown because of the potential risk of hepatitis B virus (HBV) reactivation. This study was to compare the HBV reactivation between patients with low HBV-DNA loads and high HBV-DNA loads undergoing antiviral prophylaxis and PD-1 inhibitor.

Methods: This was a retrospective study including consecutive hepatitis B surface antigen-positive HCC patients who received PD-1 inhibitor and concurrent antiviral prophylaxis for prevention of clinical hepatitis. Patients were divided into low HBV-DNA group (low group, ≤ 500 IU/ml) and high HBV-DNA group (high group, > 500 IU/ml) according to the baseline HBV-DNA level. The incidences of HBV reactivation, HBV-associated hepatitis, and PD-1 inhibitor disruption were compared between the two groups.

Results: Two hundred two eligible patients were included: 94 in the low group and 108 in the high group. Seven patients (5 in the low group and 2 in the high group) developed HBV reactivation, and all recovered from HBV reactivation and HBV-associated hepatitis. The incidence of HBV reactivation in the two groups was low (5.3% vs 1.9%, P = 0.34). There was also no difference in the incidence of HBV-associated hepatitis (P = 0.56), or PD-1 inhibitor disruption (P = 0.82). The multivariable analysis showed PD-1 inhibitor with hepatic arterial infusion chemotherapy was the only significant risk factor for HBV reactivation (P = 0.04) and hepatitis (P = 0.002).

Conclusion: With concurrent antiviral prophylaxis, HBV-DNA load higher than 500 IU/ml should not be a contraindication for PD-1 inhibitor.

Keywords: Antiviral prophylaxis; Hepatic arterial infusion chemotherapy; Hepatitis B virus reactivation; Hepatocellular carcinoma; Programmed cell death protein-1 inhibitor.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / virology*
  • DNA, Viral / blood*
  • Female
  • Hepatitis B / epidemiology
  • Hepatitis B / prevention & control
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / physiology
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Incidence
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Viral Load
  • Virus Activation / drug effects*

Substances

  • Antiviral Agents
  • DNA, Viral
  • Immune Checkpoint Inhibitors