Abstract
Background
Little is known about stopping rules of nucelos(t)ide analog (NA) treatment for chronic hepatitis B (CHB).
Methods
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.
Results
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.
Conclusion
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.
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Abbreviations
- HBV:
-
Hepatitis B virus
- CHB:
-
Chronic hepatitis B
- PEG-IFN:
-
Pegylated interferon
- NA:
-
Nucelos(t)ide analog
- HBsAg:
-
Hepatitis B surface antigen
- AASLD:
-
American Association for the Study of Liver Disease
- EASL:
-
European Association for the Study of the Liver
- APASL:
-
Asian-Pacific Association for the Study of the Liver
- LAM:
-
Lamivudine
- ETV:
-
Entecavir
- PCR:
-
Polymerase chain reaction
- VR:
-
Virological relapse
- ALT:
-
Alanine aminotransferase
- ULN:
-
Upper limit of normal
- HBcrAg:
-
HBV core-related antigen
- IP-10:
-
Interferon gamma-induced protein 10
- LS:
-
Liver stiffness
- AST:
-
Aspartate aminotransferase
- kPa:
-
Kilopascals
- IQR:
-
Interquartile range
- IQR/M:
-
IQR to median value ratio
- SD:
-
Standard deviation
- OR:
-
Odd ratio
- CI:
-
Confidence interval
- TDF:
-
Tenofovir
- cccDNA:
-
Covalently closed circular DNA
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Acknowledgments
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).
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Kyu Sik Jung and Jun Yong Park have equally contributed to this work.
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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;
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Jung, K.S., Park, J.Y., Chon, Y.E. et al. Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients. J Gastroenterol 51, 830–839 (2016). https://doi.org/10.1007/s00535-015-1153-1
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DOI: https://doi.org/10.1007/s00535-015-1153-1