Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients
Yee Hui Yeo 1 , Tai-Chung Tseng, Tetsuya Hosaka, Chris Cunningham, James Yan Yue Fung, Hsiu J Ho, Min-Sun Kwak, Huy N Trinh, Teerapat Ungtrakul, Ming-Lung Yu, Mariko Kobayashi, An K Le, Linda Henry, Jiayi Li, Jian Zhang, Tassanee Sriprayoon, Donghak Jeong, Tawesak Tanwandee, Ed Gane, Ramsey C Cheung, Chun-Ying Wu, Anna S Lok, Hyo-Suk Lee, Fumitaka Suzuki, Man-Fung Yuen, Jia-Horng Kao, Hwai-I Yang, Mindie H Nguyen
Affiliation
1 1Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA; 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 3Department of Hepatology, Toranomon Hospital, Tokyo, Japan; 4Research Centre for Maori Health and Development, Massey University, Wellington, New Zealand; 5The Hepatitis Foundation of New Zealand, Whakatane, New Zealand; 6Department of Medicine, The University of Hong Kong, Hong Kong, China; 7Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan; 8Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Korea; 9San Jose Gastroenterology, San Jose, California, USA; 10Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand; 11Hepatobiliary Section, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 12Center for Liver Research, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 13Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; 14Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan; 15Palo Alto Medical Foundation, Mountain View Division, Palo Alto, California, USA; 16Chinese Hospital, San Francisco, California, USA; 17School of Nursing, University of California, San Francisco, San Francisco, California, USA; 18Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 19New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand; 20Department of Medicine, University of Auckland, Auckland, New Zealand; 21Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA; 22College of Public Health, China Medical University, Taichung, Taiwan; 23Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA; 24Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 25Genomics Research Center, Academia Sinica, Taipei, Taiwan; 26Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Introduction: Spontaneous hepatitis B surface antigen (HBsAg) seroclearance, the functional cure of hepatitis B infection, occurs rarely. Prior original studies are limited by insufficient sample size and/or follow-up, and recent meta-analyses are limited by inclusion of only study-level data and lack of adjustment for confounders to investigate HBsAg seroclearance rates in most relevant subgroups. Using a cohort with detailed individual patient data, we estimated spontaneous HBsAg seroclearance rates through patient and virologic characteristics.
Methods: We analyzed 11,264 untreated patients with chronic hepatitis B with serial HBsAg data from 4 North American and 8 Asian Pacific centers, with 1,393 patients with HBsAg seroclearance (≥2 undetectable HBsAg ≥6 months apart) during 106,192 person-years. The annual seroclearance rate with detailed categorization by infection phase, further stratified by hepatitis B e antigen (HBeAg) status, sex, age, and quantitative HBsAg (qHBsAg), was performed.
Results: The annual seroclearance rate was 1.31% (95% confidence interval: 1.25-1.38) and over 7% in immune inactive patients aged ≥55 years and with qHBsAg <100 IU/mL. The 5-, 10-, 15-, and 20-year cumulative rates were 4.74%, 10.72%, 18.80%, and 24.79%, respectively. On multivariable analysis, male (adjusted hazard ratio [aHR] = 1.66), older age (41-55 years: aHR = 1.16; >55 years: aHR = 1.21), negative HBeAg (aHR = 6.34), and genotype C (aHR = 1.82) predicted higher seroclearance rates, as did lower hepatitis B virus DNA and lower qHBsAg (P < 0.05 for all), and inactive carrier state.
Discussion: The spontaneous annual HBsAg seroclearance rate was 1.31%, but varied from close to zero to about 5% among most chronic hepatitis B subgroups, with older, male, HBeAg-negative, and genotype C patients with lower alanine aminotransferase and hepatitis B virus DNA, and qHBsAg independently associated with higher rates (see Visual Abstract, Supplementary Digital Content 2, http://links.lww.com/CTG/A367). 作者: StephenW 时间: 2020-10-26 17:23