Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients
- 1.2k Downloads
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.
KeywordsChronic hepatitis B Antiviral treatment Nucleos(t)ide analogue Durability Relapse
Hepatitis B virus
Chronic hepatitis B
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
Upper limit of normal
HBV core-related antigen
Interferon gamma-induced protein 10
IQR to median value ratio
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.
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.
- 18.Liu F, Wang L, Li XY, Liu YD, Wang JB, Zhang ZH, et al. Poor durability of lamivudine effectiveness despite stringent cessation criteria: a prospective clinical study in hepatitis B e antigen-negative chronic hepatitis B patients. J Gastroenterol Hepatol. 2011;26(3):456–60.CrossRefPubMedGoogle Scholar
- 27.Mealing S, Ghement I, Hawkins N, Scott DA, Lescrauwaet B, Watt M, et al. The importance of baseline viral load when assessing relative efficacy in treatment-naive HBeAg-positive chronic hepatitis B: a systematic review and network meta-analysis. Syst Rev. 2014;3:21.CrossRefPubMedPubMedCentralGoogle Scholar
- 32.Jaroszewicz J, Ho H, Markova A, Deterding K, Wursthorn K, Schulz S, et al. Hepatitis B surface antigen (HBsAg) decrease and serum interferon-inducible protein-10 levels as predictive markers for HBsAg loss during treatment with nucleoside/nucleotide analogues. Antivir Ther. 2011;16(6):915–24.CrossRefPubMedGoogle Scholar