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Meta-Analysis
. 2022 Nov 11;226(10):1761-1770.
doi: 10.1093/infdis/jiac168.

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

Amir M Mohareb  1   2   3 , Anne F Liu  3   4 , Arthur Y Kim  2   3 , Patrick A Coffie  5   6 , Menan Gérard Kouamé  6 , Kenneth A Freedberg  1   2   3   7 , Anders Boyd  8   9 , Emily P Hyle  1   2   3
Affiliations
Meta-Analysis

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

Amir M Mohareb et al. J Infect Dis. .

Abstract

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.

Keywords: chronic hepatitis B infection; hepatitis B e antigen; hepatitis B e antigen clearance; natural history.

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Conflict of interest statement

Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1.
Figure 1.
Flow chart of article selection. Abbreviations: HBeAg, hepatitis B e antigen; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus.
Figure 2.
Figure 2.
Pooled incidence rate of hepatitis B e antigen (HBeAg) loss (per 100 person-years) in untreated persons with chronic hepatitis B virus [20–45]. Annual rates were combined using a random-effects model with log transformation. The vertical dashed line represents the pooled rate. Heterogeneity parameters are shown with χ2 degrees of freedom and I2 statistic. Abbreviation: CI, confidence interval.
Figure 3.
Figure 3.
Pooled rate of hepatitis B virus e antigen (HBeAg) loss (per 100 person-years) in untreated persons with chronic hepatitis B virus, stratified by region [20–45]. Heterogeneity parameters for each subgroup are shown with χ2 degrees of freedom and I2 statistic. Test for difference between subgroups showed Q = 95.22 and P < .001. Abbreviation: CI, confidence interval.
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