HBcrAg is a predictor of post-treatment recurrence of hepatocellular carcinoma during antiviral therapy.
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.
Hosaka
Tetsuya
T
Department of Hepatology, Toranomon Hospital, Tokyo, Japan. hosa-p@toranomon.gr.jp
Suzuki
Fumitaka
F
Kobayashi
Masahiro
M
Hirakawa
Miharu
M
Kawamura
Yusuke
Y
Yatsuji
Hiromi
H
Sezaki
Hitomi
H
Akuta
Norio
N
Suzuki
Yoshiyuki
Y
Saitoh
Satoshi
S
Arase
Yasuji
Y
Ikeda
Kenji
K
Kobayashi
Mariko
M
Kumada
Hiromitsu
H
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
D000998:Antiviral Agents; D006511:Hepatitis B Antigens; D063065:Organophosphonates; D012367:RNA, Viral; D019259:Lamivudine; C413685:entecavir; D006147:Guanine; D000225:Adenine; C106812:adefovir dipivoxil