Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis

Background & Aims: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. Methods: We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model. Results: We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79–1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49–5.93), 8.16% at 10 years (95% CI, 5.24–11.72), and 17.99% at 15 years (95% CI, 6.18–23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76–2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25–0.59) (P <.01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log ₁₀ IU/mL; 95% CI, 5.94–7.27) vs not having HBsAg seroclearance (7.71 log ₁₀ IU/mL; 95% CI, 7.41–8.02) (P <.01) and with a lower level of HBsAg at baseline (2.74 log ₁₀ IU/mL; 95% CI, 1.88–3.60) vs not having HBsAg seroclearance (3.90 log ₁₀ IU/mL, 95% CI, 3.73–4.06) (P <.01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I ² = 97.49%). Conclusion: In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.