title: Relationship between HBsAg, HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy.
abstract: We examined the relationship between hepatitis B surface and core-related antigens (HBsAg, HBcrAg) and hepatocellular carcinoma (HCC) development in patients with undetectable serum HBV DNA receiving nucleos(t)ide analogue (NA). Seventy-six HBV carriers with undetectable HBV DNA (<20 IU/mL) who subsequently developed HCC were compared with 152 matched controls. Clinical and laboratory parameters (including novel assays to measure linearized HBsAg [HQ-HBsAg] and HBcrAg) were analysed. There were no significant differences in HBsAg/HQ-HBsAg levels between the two groups. There was a significant difference in the median values of both pre- and post-NA HBcrAg levels between the HCC and control groups (pre-treatment: 279.0 vs 35.4 kU/mL, P=.005; post-treatment: 10.2 vs 1.7 kU/mL, P=.005, respectively). For the whole HCC group, a cut-off value of post-treatment HBcrAg level ≥7.8 kU/mL yielded an area under receiver operating curve (AUROC) of 0.61 with a negative predictive value (NPV) of 77.0%. The OR of HCC development was 3.27. For noncirrhotic patients, the median values of post-treatment HBcrAg level of HCC group and controls were 10.2 and 1.0 kU/mL, respectively (P=.001). A cut-off value of HBcrAg level ≥7.9 kU/mL yielded an AUROC of 0.70 with a NPV of 80.6%. The OR of HCC development was 5.95. A higher pre- and post-NA treatment HBcrAg level (but not HBsAg) was associated with an increased risk of HCC development in patients achieving undetectable serum HBV DNA while on NA therapy. HBcrAg may serve as a novel risk marker for HCC in this group of patients.
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
authors.forename: K-S
authors.initials: KS
authors.lastname: Cheung
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: W-K
authors.initials: WK
authors.lastname: Seto
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: D K-H
authors.initials: DK
authors.lastname: Wong
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: C-L
authors.initials: CL
authors.lastname: Lai
authors.affiliation: Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.|State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
authors.forename: M-F
authors.identifier: 0000-0001-7985-7725
authors.initials: MF
authors.lastname: Yuen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000821:virology*; D015331:Cohort Studies; D004247:DNA; D005260:Female; D006512:Hepatitis B Core Antigens / Q000097:blood*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D019694:Hepatitis B, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009705:Nucleosides / Q000627:therapeutic use; D009711:Nucleotides / Q000627:therapeutic use; D011379:Prognosis; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D009705:Nucleosides; D009711:Nucleotides; D004247:DNA
keywords: 
  HCC
  ; NA therapy; hepatitis B core-related antigen