title: HBcrAg predicts hepatocellular carcinoma development: An analysis using time-dependent receiver operating characteristics.
abstract: Several hepatitis B virus (HBV) markers have been identified as factors associated with the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We clarified the predictive power of HBV markers for the development of HCC using receiver operating characteristic (ROC) analysis with a consideration of time dependence.
  
  
  
  A total of 1031 CHB patients who were not treated with nucleos(t)ide analogue therapy were enrolled. Univariate, multivariate, and time-dependent ROC curves for HBV markers associated with the development of HCC were analyzed.
  
  
  
  Seventy-eight patients developed HCC during the follow-up period (median duration 10.7years). Different levels or statuses of several HBV markers (HBV genotype, HBV DNA, HBV core-related antigen (HBcrAg), hepatitis B e antigen (HBeAg), and basal core promoter (BCP)), but not hepatitis B surface antigen, were significantly associated with the incidence of HCC by univariate analysis using the log-rank test. Cox proportional hazards models using the covariates of HBV genotype status, HBV DNA levels, HBcrAg levels, HBeAg status, and BCP status indicated that HBcrAg >2.9logU/ml (hazard ratio (HR), 5.05; 95% confidence interval (CI), 2.40-10.63) and BCP mutation (HR, 28.85; 95% CI, 4.00-208.20) were independently associated with the incidence of HCC. Additionally, time-dependent ROC analysis showed that HBcrAg was superior to HBV DNA in terms of predictive power for HCC development throughout the follow-up period.
  
  
  
  Elevation of HBcrAg levels in CHB patients is associated with the development of HCC. HBcrAg is an excellent predictor of HCC development.
  
  
  
  Hepatitis B virus (HBV) core-related antigen (HBcrAg) is an excellent predictor of hepatocellular carcinoma (HCC) development in chronic hepatitis B patients without nucleos(t)ide analogue therapy. HBcrAg was superior to HBV DNA in terms of predictive power for HCC development by time-dependent receiver operating characteristic analysis.
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan. Electronic address: tadat0627@gmail.com.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tada
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kumada
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Toyoda
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Seiki
authors.initials: S
authors.lastname: Kiriyama
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tanikawa
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hisanaga
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kanamori
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Shusuke
authors.initials: S
authors.lastname: Kitabatake
authors.affiliation: Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, Ogaki, Gifu, Japan.
authors.forename: Tsuyoki
authors.initials: T
authors.lastname: Yama
authors.affiliation: Department of Epidemiology, Infectious Disease Control, and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D006528:Carcinoma, Hepatocellular; D004279:DNA, Viral; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic; D006801:Humans; D008113:Liver Neoplasms; D012372:ROC Curve; D012307:Risk Factors
chemical_list: D004279:DNA, Viral
keywords: Hepatitis B; Hepatitis B virus core-related antigen; Hepatocellular carcinoma; Time-dependent receiver operating characteristic