Molecular and Genomic Epidemiology Center, China Medical University Hospital, Taichung, Taiwan.
Clin Gastroenterol Hepatol. 2012 May;10(5):527-34.e1-2. doi: 10.1016/j.cgh.2011.12.019. Epub 2011 Dec 16.
BACKGROUND & AIMS: The spontaneous seroclearance of hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA are important markers of progression of chronic HBV infection. We performed a long-term cohort study to elucidate the incidence and determinants of HBeAg and HBV DNA seroclearance in patients with chronic hepatitis B.
A total of 1289 participants with a serum HBV DNA level of 10,000 copies/mL or more and without cirrhosis when the study began (1991-1992) were followed up until June 2004. A subset of patients that tested positive for HBeAg at baseline (n = 439) was included in the analysis of HBeAg seroclearance. Cox proportional hazards models were used to estimate seroclearance rate ratios for various determinants associated with the outcomes.
After 3161.2 person-years of follow-up evaluation, HBeAg seroclearance occurred in 187 participants (incidence rate, 5.9 per 100 person-years). The cumulative lifetime incidence of HBeAg seroclearance among patients who were 30 to 40, or 50, 60, 70, or 74 years old was 38.8%, 69.4%, 81.9%, 89.1%, and 95.5%, respectively. Major predictors of HBeAg seroclearance included female sex, genotype B, the precore 1896 mutant, increased serum levels of alanine aminotransferase, and low baseline serum levels of HBV DNA. The median (interquartile range) serum level of HBV DNA at the time of HBeAg seroclearance was 177,801 copies/mL (4941-3,247,560 copies/mL). HBV DNA seroclearance occurred in 199 participants (15.4%) during the mean follow-up period of 7.8 years (incidence rate, 1.97 per 100 person-years). The cumulative lifetime incidence of HBV DNA seroclearance at 40, 50, 60, 70, and 77 years old was 10.0%, 25.0%, 38.8%, 54.2%, and 82.8%, respectively. Lower levels of HBV DNA at study entry and among those with the precore 1896 wild-type variant were associated with an increased rate of HBV DNA seroclearance. Among individuals who were HBeAg-seropositive at study entry and cleared serum HBV DNA during the follow-up period, 89% had cleared HBeAg by the time they had an undetectable serum level of HBV DNA.
Serum level of HBV DNA is the most important predictor of seroclearance of HBeAg and HBV DNA. This finding supports current clinical guidelines for antiviral treatments of chronic hepatitis B.
乙型肝炎 e 抗原（HBeAg）和乙型肝炎病毒（HBV）DNA 的自发血清清除是慢性 HBV 感染进展的重要标志物。我们进行了一项长期队列研究，以阐明慢性乙型肝炎患者中 HBeAg 和 HBV DNA 血清清除的发生率和决定因素。
共有 1289 名研究开始时血清 HBV DNA 水平为 10,000 拷贝/ml 或更高且无肝硬化的患者接受随访，随访至 2004 年 6 月。在基线时 HBeAg 检测呈阳性的患者亚组（n=439）被纳入 HBeAg 血清清除分析。Cox 比例风险模型用于估计与结局相关的各种决定因素的血清清除率比。
经过 3161.2 人年的随访评估，187 名患者发生 HBeAg 血清清除（发生率为 5.9/100 人年）。30 至 40 岁、50 岁、60 岁、70 岁和 74 岁的患者终生发生 HBeAg 血清清除的累积发生率分别为 38.8%、69.4%、81.9%、89.1%和 95.5%。HBeAg 血清清除的主要预测因素包括女性、基因型 B、前核心 1896 突变、血清丙氨酸氨基转移酶水平升高和基线 HBV DNA 水平较低。HBeAg 血清清除时 HBV DNA 的中位（四分位距）血清水平为 177,801 拷贝/ml（4941-3,247,560 拷贝/ml）。在平均 7.8 年的随访期间（发生率为 1.97/100 人年），199 名患者（15.4%）发生了 HBV DNA 血清清除。40、50、60、70 和 77 岁时 HBV DNA 血清清除的累积终生发生率分别为 10.0%、25.0%、38.8%、54.2%和 82.8%。研究开始时 HBV DNA 水平较低和前核心 1896 野生型变异与 HBV DNA 血清清除率增加相关。在研究期间 HBeAg 血清阳性且清除 HBV DNA 的患者中，89%的患者在 HBV DNA 血清水平不可检测时清除了 HBeAg。
HBV DNA 血清水平是 HBeAg 和 HBV DNA 血清清除的最重要预测因素。这一发现支持当前慢性乙型肝炎抗病毒治疗的临床指南。
