Journal of Gastroenterology

, Volume 52, Issue 3, pp 366–375 | Cite as

The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients

  • Ayako Urabe
  • Michio Imamura
  • Masataka Tsuge
  • Hiromi Kan
  • Hatsue Fujino
  • Takayuki Fukuhara
  • Keiichi Masaki
  • Tomoki Kobayashi
  • Atsushi Ono
  • Takashi Nakahara
  • Tomokazu Kawaoka
  • Akira Hiramatsu
  • Yoshiiku Kawakami
  • Hiroshi Aikata
  • Clair Nelson Hayes
  • Noboru Maki
  • Hideaki Ohdan
  • Kazuaki ChayamaEmail author
Original Article—Liver, Pancreas, and Biliary Tract



Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases.


Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed.


Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325).


HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.


Liver transplantation HBV reinfection HBcrAg HBs gene mutations Hepatitis B immune globulin 





Alanine aminotransferase


Basal core promoter


Covalently closed circular


Chemiluminescence enzyme immunoassay




Hepatitis B core antigen


Hepatitis B core-related antigen


Hepatitis B e antigen


Hepatitis B immune globulin


Hepatocellular carcinoma


Hepatitis B surface antigen


Anti-hepatitis B surface antibody


Hepatitis B virus


Hepatitis C virus




Liver transplantation


Nucleos(t)ide analogue


Peripheral blood mononuclear cells


Polymerase chain reaction


Transcription-mediated amplification assay



The authors thank Rie Akiyama for expert technical help and Akemi Sata and Emiko Nishio for technical assistance.

Compliance with ethical standards

Conflict of interest

Kazuaki Chayama received honoraria from MSD K.K., Bristol-Meyers Squibb, Gilead Sciences, and AbbVie; and research funding from Dainippon Sumitomo Pharma, TORAY, Eisai, Otsuka Pharma, Mitsubishi Tanabe Pharma, Daiichi Sankyo, and Bristol-Meyers Squibb. Michio Imamura received honoraria and research funding from Bristol-Meyers Squibb. Masataka Tsuge received research funding from Bristol-Meyers Squibb.


This research is partially supported by research funding from the Research Program on Hepatitis from the Japan Agency for Medical Research and Development, AMED (Grant Number: 15fk0210001h0002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study.

Supplementary material

535_2016_1240_MOESM1_ESM.tiff (1.5 mb)
Supplementary Fig. 1. The clinical course of Case 3. The patient experienced HCC recurrence and HBsAg reappearance after LT. HBsAg reappearance was linked closely with HCC recurrence (TIFF 1521 kb)


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Copyright information

© Japanese Society of Gastroenterology 2016

Authors and Affiliations

  • Ayako Urabe
    • 1
  • Michio Imamura
    • 1
  • Masataka Tsuge
    • 1
  • Hiromi Kan
    • 1
  • Hatsue Fujino
    • 1
  • Takayuki Fukuhara
    • 1
  • Keiichi Masaki
    • 1
  • Tomoki Kobayashi
    • 1
  • Atsushi Ono
    • 1
  • Takashi Nakahara
    • 1
  • Tomokazu Kawaoka
    • 1
  • Akira Hiramatsu
    • 1
  • Yoshiiku Kawakami
    • 1
  • Hiroshi Aikata
    • 1
  • Clair Nelson Hayes
    • 1
  • Noboru Maki
    • 2
  • Hideaki Ohdan
    • 3
  • Kazuaki Chayama
    • 1
    Email author
  1. 1.Department of Gastroenterology and Metabolism, Applied Life ScienceInstitute of Biomedical and Health Science, Hiroshima University, Hiroshima UniversityHiroshimaJapan
  2. 2.Advanced Life Science Institute, Inc.WakoJapan
  3. 3.Division of Frontier Medical Science, Department of Surgery, Programs for Biomedical ResearchGraduate School of Biomedical Science, Hiroshima UniversityHiroshimaJapan

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