Impact of non-neoplastic vs intratumoural hepatitis B viral DNA and replication on hepatocellular carcinoma recurrence

Qin Wang, Luan Lin, Seungyeul Yoo, Wenhui Wang, Sima Blank, M. Isabel Fiel, Hena Kadri, Wei Luan, Leslie Warren, Jun Zhu, Spiros P. Hiotis

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Background: This study aims to determine the impact of intracellular hepatitis B virus (HBV) DNA, covalently closed circular DNA (cccDNA) and viral replicative activity in both tumour and non-neoplastic liver on prognosis and to determine the relationship of viral replicative activity and Ishak fibrosis in predicting outcome following resection. Methods: A total of 99 prospectively enrolled patients treated with primary liver resection for HBV-HCC are included. Intracellular HBV DNA and cccDNA were quantitated by real-time PCR. The RNA-sequencing (RNA-seq) was performed in a subset of 21 patients who had either minimal liver fibrosis (Ishak stages 0-2) or end-stage fibrosis (Ishak stage 6). Results: Tumour tissue contained a lower cccDNA copy number compared with paired non-neoplastic liver, and larger tumours (>3 cm) had less cccDNA compared with small tumours (≤3 cm). High viral replicative activity in non-neoplastic liver was associated with higher HCC recurrence rate independent of Ishak fibrosis stage. Genes correlated with viral replicative activity in non-neoplastic liver (620 genes) were distinct from those associated with end-stage fibrosis (1226 genes). Genes associated with viral replicative activity were preferentially distributed in regions on chr3, chr16 and chr19. Conclusions: Viral replicative activity in non-neoplastic liver is associated with HCC recurrence through mechanisms that are distinct from and independent of Ishak fibrosis stage.

Original languageEnglish
Pages (from-to)841-847
Number of pages7
JournalBritish Journal of Cancer
Volume115
Issue number7
DOIs
StatePublished - 27 Sep 2016

Keywords

  • HBV DNA
  • cccDNA
  • fibrosis
  • recurrence
  • viral replicative activity

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