title: Serum hepatitis B virus DNA before liver transplantation correlates with HBV reinfection rate even under successful low-dose hepatitis B immunoglobulin prophylaxis.
abstract: OBJECTIVE
  The combination of hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogues has been accepted as the best treatment to control hepatitis B recurrence after orthotopic liver transplantation (OLT). However, the optimal dose of HBIg remains unclear. We have previously reported that high-dose HBIg in the early period followed by low-dose HBIg with nucleos(t)ide analogues offers reliable and cost-effective control of hepatitis B recurrence. The aim of this study was to investigate intrahepatic hepatitis B virus (HBV) reinfection status with our clinically successful protocol.
  
  
  METHODS
  We quantified levels of intrahepatic HBV covalently closed circular (ccc) deoxyribonucleic acid (DNA) and serum hepatitis B core-related antigen (HBcrAg), a new serological marker that can estimate intrahepatic cccDNA levels. Nucleos(t)ide analogues were administered in all cases.
  
  
  RESULTS
  No patients showed recurrence of hepatitis B surface antigen (HBsAg) or HBV-DNA. However, HBV, cccDNA, and HBcrAg were positive in 57% and 48% of patients after OLT, respectively. Pre-OLT serum HBV-DNA and HBcrAg levels correlated linearly with post-OLT cccDNA levels (r= 0.534,P< 0.05, andr= 0.634,P< 0.05, respectively). High serum HBV-DNA and HBcrAg levels, particularly with >3 log10copies/mL and >4 log10IU/mL, respectively, at the time of OLT, were associated with high levels of post-OLT cccDNA. Even with our successful protocol, nearly half of patients showed HBV reinfection.
  
  
  CONCLUSIONS
  Patients with high serum HBV-DNA and HBcrAg levels before OLT (particularly >3 log10copies/mL and >4 log10IU/mL, respectively) should be followed with care for HBV recurrence.
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yasunaka
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Takaki
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Yagi
authors.affiliation: Health Service Center, Okayama University, Okayama, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sadamori
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tatsukawa
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kawai
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Shiraha
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miyake
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Fusao
authors.initials: F
authors.lastname: Ikeda
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kobashi
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Shinoura
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Yoshida
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Satoh
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Utsumi
authors.affiliation: Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Teppei
authors.initials: T
authors.lastname: Onishi
authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yamamoto