Yee Hui YeoHsiu J. HoHwai I. YangTai Chung TsengTetsuya HosakaHuy N. TrinhMin Sun KwakYoung Min ParkJames Yan Yue FungMaria ButiManuel RodríguezSombat TreeprasertsukCarmen Monica PredaTeerapat UngtrakulPhunchai CharatcharoenwitthayaXiangyong LiJiayi LiJian ZhangMichael Huan LeBin WeiBiyao ZouAn LeDonghak JeongNicholas ChienLeslie KamChiao Chin LeeMar Riveiro-BarcielaDoina IstratescuTassanee SriprayoonYutian ChongTawesak TanwandeeMariko KobayashiFumitaka SuzukiMan Fung YuenHyo Suk LeeJia Horng KaoAnna S. LokChun Ying WuMindie H. NguyenAcademia Sinica, Genomics Research CenterDaejin Medical CenterCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y DigestivasNational Taiwan University HospitalPalo Alto Medical FoundationChulalongkorn UniversityUniversity of Michigan, Ann ArborNational Taiwan University College of MedicineUniversity of California, San FranciscoSun Yat-Sen UniversitySeoul National University HospitalHospital Universitario Central de AsturiasToranomon HospitalStanford University Medical CenterVeterans General Hospital-TaipeiInstitutul Clinic FundeniHospital Universitari Vall d'HebronKaohsiung Medical UniversityTriservice General Hospital TaiwanFaculty of Medicine, Siriraj Hospital, Mahidol UniversityChina Medical University TaichungThe University of Hong KongChulabhorn Royal AcademyChinese HospitalSan Jose Gastroenterology2020-01-272020-01-272019-02-01Gastroenterology. Vol.156, No.3 (2019), 635-646.e915280012001650852-s2.0-85060987197https://repository.li.mahidol.ac.th/handle/20.500.14594/51942© 2019 AGA Institute 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.Mahidol UniversityMedicineArticleSCOPUS10.1053/j.gastro.2018.10.027