title: Quantitative Levels of Hepatitis B Virus DNA and Surface Antigen and the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Receiving Long-Term Nucleos(t)ide Analogue Therapy.
abstract: BACKGROUND
  Serum levels of hepatitis B virus (HBV) DNA are an important predictor of the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. However, little is known about whether high levels of hepatitis B surface antigen (HBsAg) increase the risk for HCC.
  
  
  METHODS
  We investigated 167 patients who were treated with nucleos(t)ide analogues (NA) for at least 2 years (median: 5.8 years, range: 2-13.1 years). Relationships between reduced levels of HBsAg and various factors were evaluated. In addition, we evaluated the usefulness of quantitative serum levels of HBV DNA and HBsAg as predictors of HCC development in patients receiving long-term NA therapy.
  
  
  RESULTS
  HCC developed in 9 of the 167 NA-treated patients. In the 9 patients with HCC, HBV DNA was undetectable (<2.1 log copies/mL), but HBsAg levels were ≥2000 C.O.I. in 7 patients. No maternal transmission, long NA treatment period, HBV DNA levels <3.0 log copies/mL, and reduced hepatitis B e antigen levels during the first 24 weeks of treatment were a significant factor of HBsAg levels <2000 C.O.I..
  
  
  CONCLUSIONS
  Hepatocarcinogenesis was observed in patients with high HBsAg levels, despite the negative conversion of HBV DNA as a result of long-term NA therapy. Therefore, to suppress hepatocarcinogenesis, it is important to control not only HBV DNA levels but also HBsAg levels.
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Miwa
authors.initials: M
authors.lastname: Kawanaka
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Nishino
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Oka
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Noriyo
authors.initials: N
authors.lastname: Urata
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Suehiro
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kawamoto
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University School of Medicine, Osaka, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Department of General Internal Medicine 2, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
authors.forename: Gotaro
authors.initials: G
authors.lastname: Yamada
keywords: HBV DNA; Hepatitis B surface antigen; Hepatitis B virus; Hepatocellular carcinoma; Nucleos(t)ide analogues