Yee Hui Yeo1, Hsiu J Ho2, Hwai-I Yang3, Tai-Chung Tseng4, Tetsuya Hosaka5, Huy N Trinh6, Min-Sun Kwak7, Young Min Park8, James Yan Yue Fung9, Maria Buti10, Manuel Rodríguez11, Sombat Treeprasertsuk12, Carmen Monica Preda13, Teerapat Ungtrakul14, Phunchai Charatcharoenwitthaya15, Xiangyong Li16, Jiayi Li17, Jian Zhang18, Michael Huan Le1, Bin Wei1, Biyao Zou1, An Le1, Donghak Jeong1, Nicholas Chien19, Leslie Kam19, Chiao-Chin Lee20, Mar Riveiro-Barciela10, Doina Istratescu13, Tassanee Sriprayoon15, Yutian Chong16, Tawesak Tanwandee15, Mariko Kobayashi21, Fumitaka Suzuki5, Man-Fung Yuen9, Hyo-Suk Lee7, Jia-Horng Kao22, Anna S Lok23, Chun-Ying Wu24, Mindie H Nguyen25. 1. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California. 2. Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan. 3. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 4. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki, Japan. 6. San Jose Gastroenterology, San Jose, California. 7. Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Republic of Korea. 8. Hepatology Center, Department of Internal Medicine and Biomedical Research Center, Bundang Jesaeng General Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea. 9. Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. 10. Liver Unit, Hospital Universitari Vall d'Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain. 11. Liver Unit, Division of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain. 12. Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 13. Department of Gastroenterology, Clinic Fundeni Institute, Bucharest, Romania. 14. Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Thailand. 15. Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 16. Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China. 17. Palo Alto Medical Foundation, Mountain View Division, Palo Alto, California. 18. Chinese Hospital, San Francisco, California; School of Nursing, University of California, San Francisco, California. 19. Kaohsiung Medical University, Kaohsiung, Taiwan. 20. Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan. 21. Research Institute for Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki, Japan. 22. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 23. Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan. 24. Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan; College of Public Health, China Medical University, Taichung, Taiwan. Electronic address: cywu22@vghtpe.gov.tw. 25. Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California. Electronic address: mindiehn@stanford.edu.
Abstract
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 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 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 (I2 = 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.
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 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 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 (I2 = 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.
Authors: Norah A Terrault; Abdus S Wahed; Jordan J Feld; Stewart L Cooper; Mark G Ghany; Mauricio Lisker-Melman; Robert Perrillo; Richard K Sterling; Mandana Khalili; Raymond T Chung; Philip Rosenthal; Robert J Fontana; Arif Sarowar; Daryl T Y Lau; Junyao Wang; Anna S Lok; Harry L A Janssen Journal: Hepatology Date: 2022-01-26 Impact factor: 17.425
Authors: Eleanor Barnes; Philippa C Matthews; Tingyan Wang; David A Smith; Cori Campbell; Jolynne Mokaya; Oliver Freeman; Hizni Salih; Anna L McNaughton; Sarah Cripps; Kinga A Várnai; Theresa Noble; Kerrie Woods; Jane Collier; Katie Jeffery; Jim Davies Journal: BMC Infect Dis Date: 2021-06-26 Impact factor: 3.090