Department of Medicine, The University of Hong Kong, Hong Kong SAR.
State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong SAR.
Hepatology. 2018 Aug;68(2):462-472. doi: 10.1002/hep.29874. Epub 2018 Jun 6.
The significance of hepatitis B e-antigen (HBeAg) seroclearance (ESC) in the long term is not well defined. The current study aimed to determine the clinical outcomes, the factors and predictive scores for hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) seroclearance of a large cohort of patients undergoing ESC. Patients with documented ESC were followed up 3- to 6-monthly. Baseline characteristics and longitudinal laboratory results were recorded. Predictive scores for HCC (HCC-ESC) and HBsAg seroclearance (HBsAg-ESC) were derived from multivariate Cox regression models. A total of 723 patients underwent ESC with a median ESC age and follow-up of 36.0 and 18.3 years, respectively. Only 3.5% and 3.0% had persistently normal alanine aminotransferase (ALT) and HBV DNA <2logs IU/mL, respectively, after ESC. For patients with 100%, 100%-90%, 90%-50%, 50%-10%, 10%-0%, and 0% normal ALT after HBeAg seroclearance, the rate of HCC was 4.3%, 2.2%, 3.6%, 3.9%, 17.3%, and 37.2% at 20 years after ESC, respectively (P < 0.001). At 20 years after ESC, the cumulative incidence of HCC and HBsAg seroclearance was 7.9% and 13.5%, respectively, with an overall survival of 91.5%. ESC age, male sex, cirrhosis, hypoalbuminemia, viral load, and ALT were significant factors for HCC, whereas ESC age, male sex, viral load, and antiviral therapy were significant factors for HBsAg seroclearance. The area under receiver operating characteristics for HCC-ESC and HBsAg-ESC scores to predict HCC and HBsAg seroclearance at 20 years after ESC was 0.92 and 0.74, respectively.
Male sex, older age at ESC, ALT, and higher level of HBV DNA were associated with higher rates of HCC after ESC. HCC-ESC and HBsAg-ESC predictive scores can determine the likelihood of developing HCC and achieving HBsAg seroclearance. (Hepatology 2018).
尚未明确乙型肝炎 e 抗原（HBeAg）血清学转换（ESC）长期的意义。本研究旨在确定接受 ESC 的大量患者的临床结局、发生肝细胞癌（HCC）的相关因素和预测评分，以及乙型肝炎表面抗原（HBsAg）血清学转换。有 ESC 记录的患者每 3-6 个月随访一次。记录基线特征和纵向实验室结果。使用多变量 Cox 回归模型得出 HCC（HCC-ESC）和 HBsAg 血清学转换（HBsAg-ESC）的预测评分。
共有 723 例患者接受 ESC，ESC 年龄和随访中位时间分别为 36.0 岁和 18.3 年。仅有 3.5%和 3.0%的患者 ESC 后持续正常丙氨酸氨基转移酶（ALT）和 HBV DNA<2log IU/mL。HBeAg 血清学转换后 ALT 完全正常（100%）、完全正常至 90%、90%-50%、50%-10%、10%-0%和 0%的患者，ESC 后 20 年 HCC 发生率分别为 4.3%、2.2%、3.6%、3.9%、17.3%和 37.2%（P<0.001）。ESC 后 20 年，HCC 和 HBsAg 血清学转换的累积发生率分别为 7.9%和 13.5%，总体生存率为 91.5%。ESC 年龄、男性、肝硬化、低白蛋白血症、病毒载量和 ALT 是 HCC 的显著相关因素，而 ESC 年龄、男性、病毒载量和抗病毒治疗是 HBsAg 血清学转换的显著相关因素。用于预测 ESC 后 20 年 HCC 和 HBsAg 血清学转换的 HCC-ESC 和 HBsAg-ESC 评分的受试者工作特征曲线下面积分别为 0.92 和 0.74。
ESC 后男性、ESC 年龄较大、ALT 和 HBV DNA 水平较高与 HCC 发生率升高相关。HCC-ESC 和 HBsAg-ESC 预测评分可确定发生 HCC 和实现 HBsAg 血清学转换的可能性。
