Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2021; 27(14): 1497-1506
Published online Apr 14, 2021. doi: 10.3748/wjg.v27.i14.1497
Exploration of nucleos(t)ide analogs cessation in chronic hepatitis B patients with hepatitis B e antigen loss
Yan Xue, Meng Zhang, Tao Li, Feng Liu, Li-Xin Zhang, Xiao-Ping Fan, Bao-Hua Yang, Lei Wang
Yan Xue, Meng Zhang, Tao Li, Li-Xin Zhang, Xiao-Ping Fan, Bao-Hua Yang, Lei Wang, Department of Infectious Disease and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250033, Shandong Province, China
Meng Zhang, Department of Hepatology, Jinan Infectious Disease Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250000, Shandong Province, China
Feng Liu, Department of Hepatology, Tianjin Second People’s Hospital, Tianjin 300000, China
Feng Liu, Tianjin Institute of Hepatology, Tianjin 300000, China
Xiao-Ping Fan, Department of Hepatology, Qingdao Sixth People’s Hospital, Qingdao 266100, Shandong Province, China
Author contributions: Xue Y and Zhang M contributed equally to this work; Wang L and Yang BH were senior authors and contributed equally to this work. Wang L and Yang BH contributed to the conception and design of the study; Wang L, Yang BH, Zhang LX, Liu F, Li T, Xue Y, Zhang M and Fan XP contributed to patients inclusion and follow-up; Li T, Xue Y, Zhang M and Fan XP contributed to interpretation of the data; Li T and Liu F contributed to statistical analysis of the data; Xue Y and Zhang M drafted the manuscript; Wang L, Yang BH and Liu F revised the manuscript critically.
Supported by The Shandong Province Natural Science Foundation, No. ZR2019PH052; and the National Key Research and Development Program of China, No. 2017YFC0908104.
Institutional review board statement: The study was reviewed and approved by the Second Hospital of Shandong University Institutional Review Board (Approval No. KYLL-2015(LW)-0002).
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: All authors have no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have prepared the manuscript according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Lei Wang, MD, Professor, Department of Infectious Diseases and Hepatology, The Second Hospital, Cheeloo College of Medicine, Shandong University, No. 247 Beiyuan Road, Jinan 250033, Shandong Province, China. wlsdeygbk@163.com
Received: January 14, 2021
Peer-review started: January 14, 2021
First decision: February 10, 2021
Revised: February 21, 2021
Accepted: March 17, 2021
Article in press: March 17, 2021
Published online: April 14, 2021
Abstract
BACKGROUND

Nucleos(t)ide analogs (NAs) cessation in chronic hepatitis B (CHB) patients remains a matter of debate in clinical practice. Current guidelines recommend that patients with hepatitis B e antigen (HBeAg) seroconversion discontinue NAs after relatively long-term consolidation therapy. However, many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen (HBsAg) loss occurs. It remains unclear whether NAs can be discontinued in this subset of patients.

AIM

To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss (without hepatitis B e antibody) after cessation of NAs.

METHODS

We studied patients who discontinued NAs after achieving HBeAg loss. The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs. The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves; we confirmed the cut-off value of HBsAg according to a previous study. The log-rank test was used to compare cumulative relapse rates among groups. We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates. Propensity score matching analysis (PSM) was used to balance baseline characteristics between the groups.

RESULTS

We included 83 patients with HBeAg loss. The mean age of these patients was 32.1 ± 9.5 years, and the majority was male (67.5%). Thirty-eight patients relapsed, and the cumulative relapse rate at months 3, 6, 12, 24, 36, 60, 120, and 180 were 22.9%, 36.1%, 41.0%, 43.5%, 45.0%, 45.0%, 45.0%, and 52.8%, respectively. Twenty-six (68.4%) patients relapsed in the first 3 mo after NAs cessation, and 35 patients (92.1%) relapsed in the first year after NAs cessation. Consolidation period (≥ 24 mo vs < 24 mo) (HR 0.506, P = 0.043) and HBsAg at cessation (≥ 100 IU/mL vs < 100 IU/mL) (HR 14.869, P = 0.008) were significant predictors in multivariate Cox regression. In the PSM cohort, which included 144 patients, there were lower cumulative relapse rates in patients with HBeAg seroconversion (P = 0.036).

CONCLUSION

HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation, especially in patients with HBsAg at cessation < 100 IU/mL. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.

Keywords: Chronic hepatitis B, Hepatitis B e antigen, Nucleos(t)ide analogs, Cessation

Core Tip: A considerable proportion of patients fail to achieve hepatitis B e antigen (HBeAg) seroconversion after the long-term loss of HBeAg, even if hepatitis B surface antigen loss occurs. It remains unclear whether nucleos(t)ide analogs (NAs) can be discontinued in this subset of patients. The current study included patients who discontinued NAs after achieving HBeAg loss (without hepatitis B e antibody) for long periods since 2001. It was concluded that these patients may be able to discontinue NAs therapy after long-term consolidation. HBsAg at cessation < 100 IU/mL predicts sustained virological response after NAs cessation. Careful monitoring, especially in the early stages after cessation, may ensure a favorable outcome.