Digestive Diseases and Sciences

, Volume 59, Issue 10, pp 2580–2587 | Cite as

High Risk of Hepatitis B Virus Reactivation in Nucleos(t)ide Analogue-Induced Hepatitis B e Antigen Seroconverters Older Than 40 Years

  • Li-Fu Kuo
  • Chuan-Mo Lee
  • Chao-Hung Hung
  • Jing-Houng Wang
  • Tsung-Hui Hu
  • Sheng-Nan Lu
  • Chi-Sin Changchien
  • Chien-Hung ChenEmail author
Original Article



A recent study showed that chronic hepatitis B virus (HBV) carriers with nucleos(t)ide analogue (NA)-induced hepatitis B antigen (HBeAg) seroconversion occurring before the age of 30 years have a higher risk of HBV reactivation.


To compare the risk of HBV reactivation and HBeAg seroreversion between patients with spontaneous and NA-induced HBeAg seroconversion.


A total of 135 and 251 non-cirrhotic patients with NA-induced and spontaneous HBeAg seroconversion, respectively, were analyzed.


NA-induced HBeAg seroconverters faced higher risks of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconverters (P < 0.001). In spontaneous HBeAg seroconverters, age at HBeAg seroconversion, sex, HBV DNA levels before HBeAg seroconversion, HBV genotype C, and pre-S deletions were independent predictors of HBV reactivation. In NA-induced HBeAg seroconverters, only age at baseline was an independent predictor of HBV reactivation. To determine whether the difference in the incidence of HBV reactivation or HBeAg seroreversion between two groups was age-specific, we analyzed these patients according to their age at HBeAg seroconversion (20–29, 30–39, and ≥40 years). Our data showed that NA-induced HBeAg seroconversion was an independent predictor of HBV reactivation and HBeAg seroreversion than spontaneous HBeAg seroconversion in patients older than 40 years at HBeAg seroconversion, but not in patients between 20–29 and 30–39 years of age.


NA-induced HBeAg seroconverters are associated with higher risks of HBV reactivation and HBeAg seroreversion compared to spontaneous HBeAg seroconverters, especially in patients who are older than 40 years at HBeAg seroconversion.


Nucleos(t)ide analogue Hepatitis B virus HBeAg seroconversion HBeAg seroreversion HBV reactivation 



Alanine aminotransferase




Basal core promoter


Chronic hepatitis B


Hepatitis B e antigen


Hepatitis B virus


Hepatocellular carcinoma


Nucleos(t)ide analogues


Polymerase chain reaction


Upper limit of normal



This study was supported by grants NSC 101-2314-B-182A-026 from the National Science Council.

Conflict of interest



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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Li-Fu Kuo
    • 1
  • Chuan-Mo Lee
    • 1
  • Chao-Hung Hung
    • 1
  • Jing-Houng Wang
    • 1
  • Tsung-Hui Hu
    • 1
  • Sheng-Nan Lu
    • 1
  • Chi-Sin Changchien
    • 1
  • Chien-Hung Chen
    • 1
    Email author
  1. 1.Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung and School of Medicine, College of MedicineChang Gung University, TaoyuanKaohsiungTaiwan

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