Spontaneous loss of chronic HBV infection markers in treatment-naïve children: a systematic review and pooled meta-analyses

ABSTRACT

Objectives: Chronicity could be a serious threat to hepatitis B virus (HBV)-infected children. The necessity of antiviral treatment to HBV-infected children has caused much controversy. The authors aimed to conduct a systematic review and meta-analysis of synthesized evidence regarding the spontaneous loss of chronic HBV infection markers in treatment-naïve children for exploring their long-term management.

Methods: Observational cohort studies and non-treatment arms of randomized controlled trials were searched that reported the spontaneous loss of chronic HBV infection markers in untreated children (characterized by the presence of HBsAg ≥6-month), via the rates of hepatitis B surface antigen (HBsAg) loss, hepatitis B e antigen (HBeAg) seroconversion, and HBV DNA suppression with random-effects model.

Results: Of 7,427 studies screened, 20 were included in meta-analysis. With cumulative 23,153 person-years of follow-up, the pooled annual incidences of HBsAg and HBeAg loss, HBV DNA suppression were 1, 6, 7%, respectively. Rates within HBeAg loss and HBV DNA suppression did differ by the transmission modes and ALT levels, not in HBsAg.

Conclusion: Spontaneous HBsAg loss (function cure) occurs infrequently in treatment-naïve children with chronic HBV infection. Design of practically applicable programs aiming at therapeutics of children may be necessary to support the goal of eliminating HBV infection worldwide.

KEYWORDS:

• Children
• chronic HBV infection markers
• regional endemicity
• transmission mode
• ALT level
• antiviral therapy natural history

Article highlights

• This is the first systematic study to analyze the spontaneous loss of chronic HBV infection markers in treatment-naïve children.

• Spontaneous HBsAg loss occurs infrequently (about 1% per year) in treatment-naïve children with chronic HBV infection.

• Timely and appropriate prevention strategies based on antiviral therapy could be necessary for HBV-infected children.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Study conception and design: Y Yang, Y Zhao, A Huang. Data collection: Y Yang, Y Zhao. Interpretation of results: Y Yang, A Huang, Y Zhao. Drafting the manuscript: Y Yang, Y Zhao. All authors reviewed and approved the final version of the manuscript.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was supported by the National Clinical Research Center for Child Health and Disorders General Project [No. NCRCCHD-2019-GP-04];Central Government Guides Local Science and Technology Development Projects-demonstration of Science and Technology Innovation projects, National Natural Science Foundation of China [No. 81371876];Outstanding Youth Foundation of Children’s Hospital of Chongqing Medical University.