Open Access Research article

Long-term outcomes after nucleos(t)ide analogues discontinuation in chronic hepatitis B patients with HBeAg-negative

Dengming He12, Shimin Guo1, Wen Chen1, Xianli Chen13, Guohua Yan1, Jie Wang1, Maoshi Li1, Peng Zhu1, Hongfei Huang1 and Yuming Wang1*

Author Affiliations

1 Institute of Infectious Diseases, Southwest Hospital, Third Military Medical University, Chongqing, China

2 Liver Disease Diagnoses and Therapy Center, The 88th Hospital of the Chinese PLA, Tai'an, China

3 Liver Disease Center, The 180th Hospital of the Chinese PLA, Quanzhou, China

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BMC Infectious Diseases 2013, 13:458  doi:10.1186/1471-2334-13-458

Published: 3 October 2013



Hepatitis B e Antigen (HBeAg)-negative chronic hepatitis B (CHB) patients have an active liver disease with a high risk of progression to decompensated cirrhosis and hepatocellular carcinoma. The management strategy for HBeAg-negative CHB patients treated with nucleos(t)ide analogues (NUCs) is a topic of concern. To observe the outcomes for this population after NUCs withdrawal, HBeAg-negative CHB patients with loss of hepatitis B surface antigen (HBsAg) or sustained undetectable HBV DNA levels who had discontinued NUCs therapy were included in the study.


A total of 66 patients (2 patients with HBsAg loss and 64 patients with sustained undetectable HBV DNA levels) were examined. HBV DNA levels and alanine aminotransferase (ALT) levels were monitored regularly after discontinuation of NUCs therapy. Relapse was defined as HBV DNA levels >2,000 IU/mL while off therapy in at least two determinations more than 4 weeks apart.


The time to achieve undetectable HBV DNA levels was 14 weeks (interquartile range (IQR): 12–24 weeks). The time until consolidation therapy was 144 weeks (IQR: 96–168 weeks). No relapses occurred in either of the HBsAg loss patients. Among the 64 patients with undetectable HBV DNA levels, 19 (29.7%) patients demonstrated evidence of relapse. All the relapses occurred within 96 weeks after discontinuation. The median duration of relapse was 36 weeks (IQR: 12–48 weeks). Elevation of HBV DNA and ALT levels over baseline was only observed in 10% of the relapse patients. There were no significant differences among the baseline characteristics (sex, HBV genotype, age, or ALT level) or the time until consolidation therapy between relapse and sustained-response patients.


NUC discontinuation is feasible after achieving undetectable HBV DNA levels in HBeAg-negative CHB patients. Prolonging the time until consolidation therapy may be a good strategy to decrease the rate of relapse. More than 96 weeks of sustained response is a predictive marker of long-term sustained response.

Chronic hepatitis B; HBeAg-negative; Nucleos(t)ide analogues; Discontinuation; Relapse