HBV突变株在HBeAg阳性状态的组合和演变预测HBeAg血清转换后的

StephenW

Hepatology International
June 2013, Volume 7, Issue 2, pp 477-488
Combination and evolution of HBV mutant strains in the HBeAg-positive status predict clinical outcomes after HBeAg seroconversion

    Chien-Hung Chen,
    Chuan-Mo Lee,
    Jing-Houng Wang,
    Tsung-Hui Hu,
    Chao-Hung Hung,
    Chi-Sin Changchien,
    Sheng-Nan Lu


Abstract
Purpose

We investigated whether the combined presence and evolution of hepatitis B virus (HBV) mutant strains in the hepatitis B e antigen (HBeAg)-positive status can predict clinical outcomes after HBeAg seroconversion.
Methods

One hundred and eighty-six patients with spontaneous HBeAg seroconversion were enrolled into this longitudinal study. The sequences of pre-S, core promoter, and precore regions were determined at study entry and at the visit immediately before HBeAg seroconversion.
Results

Age ≥40 years at HBeAg seroconversion, male sex, and higher HBV DNA levels at entry were independent predictors for HBeAg-negative chronic hepatitis B (CHB). Patients with combined mutations of pre-S deletions and T1762/A1764 had a significantly increased risk of cirrhosis and hepatocellular carcinoma (HCC) compared to patients with the wild type at both genomic regions. Combinations of pre-S deletions and T1762/A1764 were found on the same HBV genome by cloning analysis of full-length HBV genomes. Patients with a persistent presence of pre-S deletions and T1762/A1764 mutations, and new development of pre-S deletions in the HBeAg-positive status were significantly at an increased risk of HBeAg-negative CHB, cirrhosis, and HCC after HBeAg seroconversion than those with a persistent presence of the wild type at both genomic regions. After adjusting the other risk factors, the evolution of pre-S deletions was an independent predictor for cirrhosis [hazard ratio (HR): 1.52, 95 % confidence interval (CI) 1.02–2.25] and HCC (HR: 4.0, 95 % CI 1.6–10.1).
Conclusions

The combined presence and evolution of pre-S deletions and T1762/A1764 in the HBeAg-positive status was a useful factor significantly predictive of clinical outcomes in patients with spontaneous HBeAg seroconversion.

StephenW

我们调查是否合并存在和演化的乙肝病毒（HBV）突变株在B型肝炎e抗原（HBeAg）阳性阳性状况可以预测HBeAg血清转换后的临床结果。
方法

和86例自发性HBeAg血清转换的患者被纳入这项纵向研究。在进入研究，决定在访问之前HBeAg血清学转换的pre-S的序列，核心启动子和前C区。
结果

年龄≥40年在HBeAg血清转换，男性，和较高的HBV DNA水平进入HBeAg阴性慢性乙型肝炎（CHB）的独立预测因子。两个基因组区域与野生型的患者相比，合并前S缺失和T1762/A1764突变的患者有肝硬化和肝细胞癌（HCC）的风险显着增加。前S缺失和T1762/A1764的组合在相同的HBV基因组全长的HBV基因组的克隆分析来找到。 HBeAg血清转换后比前S缺失和T1762/A1764突变，前S缺失HBeAg阳性的状态和新的发展与持续存在的患者HBeAg阴性慢性乙型肝炎，肝硬化和肝癌的风险增加显着那些具有持久性的存在下，与野生型在这两个基因组区域。调整后的其他风险因素，前S缺失的演变是一个独立的预测肝硬化[风险比（HR）：1.52，95％可信区间（CI）1.02-2.25]和肝癌（HR：4.0，95％CI 1.6-10.1）。
结论

合并前S缺失和T1762/A1764 HBeAg阳性状态的存在和演化是一个有用的自发性HBeAg血清转换的患者显着预测临床结果的因素。