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 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 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 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.