title: Reactivation of hepatitis B virus in HBsAg-negative patients with hepatocellular carcinoma.
abstract: OBJECTIVE
  Despite increasing attention to hepatitis B virus (HBV) reactivation in hematologic settings, information on reactivation in hepatitis B surface (HBsAg)-negative patients with hepatocellular carcinoma (HCC) remains unknown. This study aimed to determine the incidence and risk factors of HBV reactivation in HBsAg-negative patients undergoing transarterial chemoembolization (TACE).
  
  
  METHODS
  A total of 109 HBsAg-negative patients with HCC were consecutively recruited for this study and treated with either mono- (n = 75), combination-drug TACE (n = 20), or combination-drug TACE plus radiotherapy (n = 14). With serial monitoring of virological markers every 2-3 months, patients were observed for HBV reactivation (defined as the reappearance of HBV DNA or sero-reversion of HBsAg) in comparison with control subjects with HBsAg-negative cirrhosis (n = 16) or HBsAg loss (n = 46).
  
  
  RESULTS
  During the study period, HBV reactivation occurred in 12 (11.0%) and 1 (1.6%) patients in the TACE and control groups, respectively. The median level of HBV DNA at reactivation was 5,174 copies/ml (range: 216-116,058). Of the 12 patients with HBV reactivation, four (33.3%) developed clinical hepatitis, including one patient who suffered from decompensation. All antiviral-treated patients achieved undetectable HBV DNA or HBsAg loss after commencement of antiviral drugs. TACE was significantly correlated with a high incidence of HBV reactivation, with increasing risk of reactivation with intensive treatment. On multivariate analysis, treatment intensity and a prior history of chronic hepatitis B remained independently predictive of reactivation.
  
  
  CONCLUSIONS
  TACE can reactivate HBV replication in HBsAg-negative patients, with a dose-risk relationship between treatment intensity and reactivation. Patients with prior chronic HBV infection who are to undergo intensive TACE should be closely monitored, with an alternative approach of antiviral prophylaxis against HBV reactivation.
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jeong Won
authors.initials: JW
authors.lastname: Jang
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Young Woon
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Kwon
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Soon Woo
authors.initials: SW
authors.lastname: Nam
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Si Hyun
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jong Young
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Seung Kew
authors.initials: SK
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea Incheon St. Mary's Hospital, Incheon, Korea.
authors.forename: Kyu Won
authors.initials: KW
authors.lastname: Chung
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D016461:Chemoembolization, Therapeutic; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000628:therapy* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014775:Virus Activation
chemical_list: D000970:Antineoplastic Agents; D006514:Hepatitis B Surface Antigens