title: Impact of non-neoplastic vs intratumoural hepatitis B viral DNA and replication on hepatocellular carcinoma recurrence.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  Viral replicative activity in non-neoplastic liver is associated with HCC recurrence through mechanisms that are distinct from and independent of Ishak fibrosis stage.
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Luan
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Seungyeul
authors.initials: S
authors.lastname: Yoo
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Sima
authors.initials: S
authors.lastname: Blank
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Fiel
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Hena
authors.initials: H
authors.lastname: Kadri
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Luan
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Warren
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY 10029, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Surgery, Icahn School of Medicine at Mount Sinai, 5 East 98th Street, 12th Floor, Box 1259, New York, NY 10029, USA.
authors.forename: Spiros P
authors.initials: SP
authors.lastname: Hiotis
mesh_terms: D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000601:surgery / Q000821:virology*; D004270:DNA, Circular / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D005838:Genotype; D006498:Hepatectomy; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000473:pathology / Q000821:virology*; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000473:pathology / Q000601:surgery / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D047368:Tumor Burden; D019562:Viral Load; D014779:Virus Replication
chemical_list: D004270:DNA, Circular; D004279:DNA, Viral