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

Abstract

Background In people with hepatitis B virus (HBV) infection, persistence of HBV “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% CI: 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 were: 7.43/100 PYs (95%CI: 6.30, 8.75; 1 study) in Africa; 3.24/100 PYs (95%CI: 2.61, 4.02; 1 study) in the Eastern Mediterranean; 13.67/100 PYs (95%CI:11.21, 16.66; 4 studies) in Europe; 7.34/100 PYs (95%CI:4.61, 11.70; 5 studies) in North America; 5.53/100 PYs (95%CI: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.

Proportion of pregnant women with HBV infection eligible for antiviral prophylaxis to prevent vertical transmission: A systematic review and meta-analysis

“…Another contributing factor to this geographical variation is the difference in circulating HBV genotypes. 35 , 36 Importantly, our study has confirmed a similar pattern of geographical variation in the proportion of pregnant women with high HBV DNA levels, providing further support for the aforementioned hypothesis.…”

“… 34 MTCT is more likely than horizontal transmission to result in chronic HBV infection. 34 In addition, among individuals who have established chronic HBV infection, MTCT further increases the risk of prolonged periods of HBeAg persistence and high HBV replication beyond the reproductive age, 35 , 36 thereby perpetuating the cycle of MTCT in subsequent generations. Another contributing factor to this geographical variation is the difference in circulating HBV genotypes.…”

Virological, serological and clinical outcomes in chronic hepatitis B virus infection: development and validation of the HEPA-B simulation model

“…Whenever possible, we used region-specific parameters from observational studies. Important parameters include rate of HBeAg loss (pooled rate, 6.46% per year),30 duration of time in HBeAg-positive chronic hepatitis (mean, 5.0 years (SD, 0.67 years)),31 and incidence of HBeAg-negative chronic hepatitis (2.56%–10.77% per year) 32. Return to HBeAg-negative chronic infection from HBeAg-negative chronic hepatitis occurs at 1.01% per year, and people remain at risk to return to HBeAg-negative chronic hepatitis 33…”

Clinical Utility of Quantitative HBV Core Antibodies for Solving Diagnostic Dilemmas

“…In patients with chronic HBV infection, HBeAg seroclearance indicates a transition from phase 2 (“immune active”) to phase 3 (“inactive carrier”) with a lower level of HBV DNA replication and reduced risk of liver disease progression. Predictors of HBeAg seroclearance to treat naïve patients of an older age, the lower level of HBV DNA, higher level of ALT, presence of Pre-C/BCP mutations and viral genotype [ 74 , 75 ]. Since the benefits of antiviral treatment in HBeAg-positive patients are still debatable, recognising the probability of spontaneous HBeAg loss may help weigh the risks and benefits of initiating therapy.…”