Clearance of Hepatitis B e Antigen in Untreated Chronic Hepatitis B Virus Infection: A Systematic Review and Meta-analysis

Amir M. Mohareb, Anne F. Liu, Arthur Y. Kim, Patrick A. Coffie, Menan G. rard Kouamé, Kenneth A. Freedberg, Anders Boyd, Emily P. Hyle

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: In people with hepatitis B virus (HBV) infection, persistence of hepatitis B e antigen (HBeAg) is associated with clinical progression and need for treatment. HBeAg loss represents partial immune control and is a critical event in the natural history of chronic HBV. METHODS: We conducted a systematic review and meta-analysis of cohort studies that report HBeAg loss among people with untreated chronic HBV. We evaluated HBeAg loss using a random-effects model and conducted subanalysis on region. RESULTS: We screened 10 560 publications, performed 196 full-text analyses, and included 26 studies for meta-analysis. The pooled rate of HBeAg loss was 6.46/100 person-years (PYs) (95% confidence interval, 5.17-8.08). Meta-regression showed that older age of participants and studies in Europe were associated with higher rate of HBeAg loss. Rates per 100 PYs were 7.43 (95% confidence interval, 6.30-8.75; 1 study) in Africa, 3.24 (2.61--4.02; 1 study) in the Eastern Mediterranean, 13.67 (11.21-16.66; 4 studies) in Europe, 7.34 (4.61--11.70; 5 studies) in North America, and 5.53 (4.05--7.55; 15 studies) in the Western Pacific. CONCLUSIONS: Spontaneous HBeAg loss occurs at a rate of 6.46/100 PYs. Variations by region and age group may reflect epidemiological, immunological, or HBV genotype-related differences.
Original languageEnglish
Pages (from-to)1761-1770
Number of pages10
JournalThe Journal of Infectious Diseases
Issue number10
Early online date2 May 2022
Publication statusPublished - 11 Nov 2022


  • chronic hepatitis B infection
  • hepatitis B e antigen
  • hepatitis B e antigen clearance
  • natural history

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