Yeo Y.H.Ho H.J.Yang H.-I.TAI-CHUNG TSENGHosaka T.Trinh H.N.Kwak M.-S.Park Y.M.Fung J.Y.Y.Buti M.Rodríguez M.Treeprasertsuk S.Preda C.M.Ungtrakul T.Charatcharoenwitthaya P.Li X.Li J.Zhang J.Le M.H.Wei B.Zou B.Le A.Jeong D.Chien N.Kam L.Lee C.-C.Riveiro-Barciela M.Istratescu D.Sriprayoon T.Chong Y.Tanwandee T.Kobayashi M.Suzuki F.Yuen M.-F.Lee H.-S.JIA-HORNG KAOLok A.S.Wu C.-Y.Nguyen M.H.2021-09-042021-09-0420190016-5085https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060987197&doi=10.1053%2fj.gastro.2018.10.027&partnerID=40&md5=646e5c5c04ac34021cc5bc857452f3f7https://scholars.lib.ntu.edu.tw/handle/123456789/581808Background & 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. ? 2019 AGA InstituteCHB; Disease Progression; Natural History; Prognosis[SDGs]SDG3hepatitis B surface antigen; virus DNA; biological marker; hepatitis B surface antigen; virus DNA; Article; chronic hepatitis B; follow up; genotype; Hepatitis B virus; human; incidence; patient counseling; priority journal; risk factor; adult; blood; chronic hepatitis B; female; immunology; isolation and purification; male; meta analysis; middle aged; prognosis; reference value; seroepidemiology; serology; Adult; Biomarkers; DNA, Viral; Female; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Middle Aged; Prognosis; Reference Values; Risk Factors; Seroepidemiologic Studies; Serologic Testsjournal article10.1053/j.gastro.2018.10.027303420342-s2.0-85060987197