title: HBcrAg is a predictor of post-treatment recurrence of hepatocellular carcinoma during antiviral therapy.
abstract: OBJECTIVE
  The recurrence rate of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is high even in patients receiving curative therapy. In this study, we analysed the risk factors for tumour recurrence after curative therapy for HBV-related HCC while under treatment with nucleot(s)ide analogues (NAs) by measuring serum HBcrAg and intrahepatic covalently closed circular DNA (cccDNA) levels to elucidate the viral status associated with HCC recurrence.
  
  
  METHODS
  We enrolled 55 patients who developed HCC during NA therapy and underwent either curative resection or percutaneous ablation for HCC.
  
  
  RESULTS
  Hepatocellular carcinoma recurred in 21 (38%) of the patients over a period of 2.2 (range, 0.2-7.4) years. In multivariate analysis, serum HBcrAg levels ≥4.8 log U/ml at the time of HCC diagnosis (hazard ratio, 8.96; 95% confidential interval, 1.94-41.4) and portal vein invasion (3.94, 1.25-12.4) were independent factors for HCC recurrence. The recurrence-free survival rates of the high cccDNA group were significantly lower than those of the low cccDNA group only in patients who underwent resection (P=0.0438). A positive correlation (P=0.028; r=0.479) was observed between the intrahepatic cccDNA and the serum HBcrAg levels at the incidence of HCC.
  
  
  CONCLUSIONS
  HBcrAg is a predictor of the post-treatment recurrence of HCC during antiviral therapy. Serum HBcrAg and intrahepatic cccDNA suppression by NAs may be important to prevent HCC recurrence.
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan. hosa-p@toranomon.gr.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hosaka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Miharu
authors.initials: M
authors.lastname: Hirakawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yatsuji
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sezaki
authors.forename: Norio
authors.initials: N
authors.lastname: Akuta
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saitoh
authors.forename: Yasuji
authors.initials: Y
authors.lastname: Arase
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000401:mortality / Q000601:surgery* / Q000821:virology; D017115:Catheter Ablation; D018572:Disease-Free Survival; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000627:therapeutic use; D006498:Hepatectomy; D006511:Hepatitis B Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007564:Japan; D053208:Kaplan-Meier Estimate; D019259:Lamivudine / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000401:mortality / Q000628:therapy* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000821:virology*; D063065:Organophosphonates / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D006511:Hepatitis B Antigens; D063065:Organophosphonates; D012367:RNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000225:Adenine; C106812:adefovir dipivoxil