Hepatitis B Virus cccDNA in Hepatocellular Carcinoma Tissue Increases the Risk of Recurrence After Liver Transplantation

Transplant Proc. 2019 Dec;51(10):3364-3368. doi: 10.1016/j.transproceed.2019.04.020. Epub 2019 Jul 26.

Abstract

Background: High hepatitis B virus (HBV) DNA level is strongly associated with hepatocellular carcinoma (HCC) development in chronic HBV infection. The aim of this study was to investigate the association between intrahepatic HBV DNA titer and post-liver transplantation (LT) prognosis for HBV-related HCC (HBV-HCC) patients.

Methods: A total of 60 patients with HBV-HCC who underwent LT were retrospectively studied. Using quantitative TaqMan fluorescent real-time polymerase chain reaction assay, HBV total DNA (tDNA) and covalently closed circular DNA (cccDNA) were both quantified in tumor tissue (TT) and adjacent non-tumor tissue (ANTT) from the explanted liver.

Results: The loads of tDNA and cccDNA in ANTT were associated with serum HBV DNA levels. Multivariate analysis showed that the presence of vascular invasion and cccDNA in TT were independent risk factors for tumor recurrence. The group of patients with cccDNA titers ≥31ogl0 copies/μg in TT had significantly higher cumulative recurrence rates than those with <31ogl0 copies/μg group. The cccDNA titers predicted the tumor recurrence with an area under the receiver operating characteristic curve of 0.664.

Conclusions: Our findings would assist the clinical implementation of a more personalized therapy for tumor recurrence control and improve the prognosis of HBV-HCC patients.

MeSH terms

  • Adult
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / virology*
  • DNA, Circular / analysis
  • DNA, Viral / analysis*
  • Female
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / surgery
  • Hepatitis B, Chronic / virology
  • Humans
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Liver Neoplasms / virology*
  • Liver Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / virology*
  • Postoperative Complications / virology*
  • Prognosis
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Risk Factors

Substances

  • DNA, Circular
  • DNA, Viral