Journal of Gastroenterology

, Volume 51, Issue 8, pp 830–839 | Cite as

Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients

  • Kyu Sik Jung
  • Jun Yong Park
  • Young Eun Chon
  • Hyon-Suk Kim
  • Wonseok Kang
  • Beom Kyung Kim
  • Seung Up Kim
  • Do Young Kim
  • Kwang-Hyub Han
  • Sang Hoon AhnEmail author
Original Article—Liver, Pancreas, and Biliary Tract



Little is known about stopping rules of nucelos(t)ide analog (NA) treatment for chronic hepatitis B (CHB).


A total of 113 consecutive patients with CHB (45 HBeAg-positive and 68 HBeAg-negative CHB patients), who met the cessation criteria of NA treatment as per the Asian-Pacific Association for the Study of the Liver (APASL) guideline, were enrolled in this prospective cohort study. The primary endpoint was to evaluate virological relapse (VR) rate within 1 year, which was defined as reappearance of hepatitis B virus (HBV)–DNA > 2000 IU/mL after cessation of NA treatment. In this cohort, entecavir was used in 81 (71.7 %) and lamivudine in 32 (28.3 %) patients.


Within 1 year after NA treatment, VR occurred in 26 (57.8 %) HBeAg-positive patients and in 37 (54.4 %) HBeAg-negative patients. In univariate and subsequent multivariate analysis, age > 40 years [odds ratio (OR) 10.959; 95 % confidence interval (CI) 2.211–54.320; P = 0.003) and a pre-treatment HBV DNA level >2000,000 IU/mL (OR 9.285; 95 % CI 1.545–55.795; P = 0.036) were identified as independent risk factors for VR in HBeAg-positive patients, and age > 40 years (OR 6.690; 95 % CI 1.314–34.057; P = 0.022) and an end-of-treatment HBcrAg level >3.7 log IU/mL (OR 3.751; 95 % CI 1.187–11.856; P = 0.024) were identified in HBeAg-negative patients. During follow up, neither hepatic decompensation nor hepatocellular carcinoma (HCC) occurred, and HBV DNA suppression was achieved in all patients who received antiviral re-treatment.


Our data suggested that the APASL stopping rule could be applied if a candidate was properly selected using individual risk factors. However, regular monitoring should be performed after cessation of NA treatment and long-term outcomes need to be evaluated further.


Chronic hepatitis B Antiviral treatment Nucleos(t)ide analogue Durability Relapse 



Hepatitis B virus


Chronic hepatitis B


Pegylated interferon


Nucelos(t)ide analog


Hepatitis B surface antigen


American Association for the Study of Liver Disease


European Association for the Study of the Liver


Asian-Pacific Association for the Study of the Liver






Polymerase chain reaction


Virological relapse


Alanine aminotransferase


Upper limit of normal


HBV core-related antigen


Interferon gamma-induced protein 10


Liver stiffness


Aspartate aminotransferase




Interquartile range


IQR to median value ratio


Standard deviation


Odd ratio


Confidence interval




Covalently closed circular DNA



The authors are grateful to Dong-Su Jang (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the figures.

Grant support

This study was supported by following Grants; (a) a fund of the HBV cohort study from the Korea Centers for Disease Control and Prevention (4800-4845-300-260, 2015-ER5101-00), (b) a faculty research Grant of Yonsei University College of Medicine (No. 6-2012-0008).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2015_1153_MOESM1_ESM.tif (8.1 mb)
Supplementary Figure 1 Cumulative relapse rate after cessation of antiviral therapy in HBeAg-positive patients (A) and HBeAg-negative patients (B). The 1-year cumulative relapse rate is not significantly different between the two groups (P > 0.05, log-rank test; TIFF 8275 kb)


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Copyright information

© Japanese Society of Gastroenterology 2015

Authors and Affiliations

  • Kyu Sik Jung
    • 1
  • Jun Yong Park
    • 1
    • 2
    • 4
  • Young Eun Chon
    • 1
  • Hyon-Suk Kim
    • 3
  • Wonseok Kang
    • 1
  • Beom Kyung Kim
    • 1
    • 2
    • 4
  • Seung Up Kim
    • 1
    • 2
    • 4
  • Do Young Kim
    • 1
    • 2
    • 4
  • Kwang-Hyub Han
    • 1
    • 2
    • 4
    • 5
  • Sang Hoon Ahn
    • 1
    • 2
    • 4
    • 5
    Email author
  1. 1.Department of Internal MedicineYonsei University College of MedicineSeoulKorea
  2. 2.Institute of GastroenterologyYonsei University College of MedicineSeoulKorea
  3. 3.Department of Laboratory MedicineYonsei University College of MedicineSeoulKorea
  4. 4.Liver Cirrhosis Clinical Research CenterSeoulKorea
  5. 5.Brain Korea 21 Project of Medical ScienceSeoulKorea

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