Department of Medicine, Stanford University Medical Center, Palo Alto, California, USA.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Clin Transl Gastroenterol. 2020 Sep;11(9):e00196. doi: 10.14309/ctg.0000000000000196.
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.
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.
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.
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).
乙型肝炎表面抗原（HBsAg）自发清除，即乙型肝炎感染的功能性治愈，很少发生。先前的原始研究受到样本量不足和/或随访时间有限的限制，而最近的荟萃分析受到仅纳入研究水平数据和缺乏对混杂因素进行调整的限制，无法调查大多数相关亚组中 HBsAg 清除率。使用具有详细个体患者数据的队列，我们根据患者和病毒学特征估计了 HBsAg 自发清除率。
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，这些患者具有来自 4 个中心的连续 HBsAg 数据，其中 1393 例患者（每隔 6 个月至少 2 次检测到 HBsAg 不可检测≥2 次）在 106192 人年中出现 HBsAg 清除（≥2 次）。通过感染期的详细分类，进一步按乙型肝炎 e 抗原（HBeAg）状态、性别、年龄和定量 HBsAg（qHBsAg）分层，进行了每年 HBsAg 清除率的分析。
每年的 HBsAg 清除率为 1.31%（95%置信区间：1.25-1.38），在免疫无活性的年龄≥55 岁且 qHBsAg <100IU/mL 的患者中超过 7%。5 年、10 年、15 年和 20 年的累积清除率分别为 4.74%、10.72%、18.80%和 24.79%。多变量分析显示，男性（调整后的危险比[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）预测清除率更高，HBV DNA 和 qHBsAg 较低（所有 P < 0.05）以及非活动携带者状态也是如此。
HBsAg 自发清除的年发生率为 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，年龄较大、男性、HBeAg 阴性和基因型 C 的患者具有较低的丙氨酸氨基转移酶和乙型肝炎病毒 DNA，以及 qHBsAg 与较高的清除率独立相关（见可视化摘要，补充数字内容 2，http://links.lww.com/CTG/A367）。
