自发性HBsAg血清清除率的发病率，因素和患者水平数据：一项

StephenW

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.
  

        
                     
            

    PMID: 33094953 PMCID: PMC7494149 DOI: 10.14309/ctg.0000000000000196

Free PMC article
Abstract

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).

StephenW

自发性HBsAg血清清除率的发病率，因素和患者水平数据：一项11264名患者的队列研究
Yee Hui Yeo 1，曾大中，保坂哲也，克里斯·坎宁安，阎跃峰，秀J Ho，闵新国，许N Trinh，Teerapat Ungtrakul，余铭龙，小林真理子，An K Le，琳达亨利，李嘉怡，张健，塔萨妮·史翠普龙，郑东鹤，塔维萨克·谭万迪，埃德·甘恩，张兰西，杨怀一，阮敏敏
隶属关系

    PMID：33094953 PMCID：PMC7494149 DOI：10.14309 / ctg.0000000000000196

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抽象

简介：自发性乙肝表面抗原（HBsAg）血清清除是乙肝感染的功能性治愈，很少发生。先前的原始研究受限于样本量和/或随访不足，而最近的荟萃分析受限于仅纳入研究水平的数据，并且缺乏对混杂因素进行调整以调查大多数相关亚组中HBsAg血清清除率的限制。使用具有详细个体患者数据的队列，我们​​通过患者和病毒学特征估计了自发性HBsAg血清清除率。

方法：我们分析了来自北美4个和亚太地区8个中心的11264例未经治疗的慢性乙型肝炎患者的一系列HBsAg数据，在106192人年期间对1393例HBsAg血清清除率（≥2个月的HBsAg≥6个月间隔）进行了分析。进行了年度血清清除率，并按感染阶段进行了详细分类，并进一步按乙型肝炎e抗原（HBeAg）状况，性别，年龄和定量HBsAg（qHBsAg）进行了分层。

结果：年龄≥55岁且qHBsAg <100 IU / mL的免疫惰性患者的年血清清除率为1.31％（95％置信区间：1.25-1.38），超过7％。 5年，10年，15年和20年累积率分别为4.74％，10.72％，18.80％和24.79％。在多变量分析中，男性（调整风险比[aHR] = 1.66），年龄较大（41-55岁：aHR = 1.16；> 55岁：aHR = 1.21），HBeAg阴性（aHR = 6.34）和基因型C（aHR） = 1.82）预测较高的血清清除率，较低的乙型肝炎病毒DNA和较低的qHBsAg（所有P均<0.05），以及携带者处于非活动状态。

讨论：自发的年度HBsAg血清清除率为1.31％，但在大多数慢性乙型肝炎亚组中，从接近零到约5％不等，其中年龄较大，男性，HBeAg阴性和基因型C患者的丙氨酸转氨酶和乙肝病毒水平较低DNA和qHBsAg独立地与更高的发生率相关（请参阅《视觉摘要》，补充数字内容2，http：//links.lww.com/CTG/A367）。

StephenW

https://journals.lww.com/ctg/Ful ... vel_Data_for.5.aspx