Chen Chien-Hung, Lee Chuan-Mo, Wang Jing-Houng, Hu Tsung-Hui, Hung Chao-Hung, Changchien Chi-Sin, Lu Sheng-Nan
Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 Ta Pei Road, Kaohsiung, Taiwan.
School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hepatol Int. 2013 Jun;7(2):477-88. doi: 10.1007/s12072-012-9381-4. Epub 2012 Jun 21.
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.
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.
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).
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.
我们研究了乙肝e抗原（HBeAg）阳性状态下乙肝病毒（HBV）突变株的联合存在及演变是否能预测HBeAg血清学转换后的临床结局。
186例自发HBeAg血清学转换的患者被纳入这项纵向研究。在研究入组时以及HBeAg血清学转换前的一次随访中测定前S区、核心启动子区和前核心区的序列。
HBeAg血清学转换时年龄≥40岁、男性以及入组时较高的HBV DNA水平是HBeAg阴性慢性乙型肝炎（CHB）的独立预测因素。与两个基因组区域均为野生型的患者相比，前S区缺失和T1762/A1764联合突变的患者发生肝硬化和肝细胞癌（HCC）的风险显著增加。通过对全长HBV基因组进行克隆分析，在前S区缺失和T1762/A1764的联合突变存在于同一HBV基因组上。与两个基因组区域均持续存在野生型的患者相比，在HBeAg阳性状态下持续存在前S区缺失和T1762/A1764突变以及新出现前S区缺失的患者在HBeAg血清学转换后发生HBeAg阴性CHB、肝硬化和HCC的风险显著增加。在对其他危险因素进行校正后，前S区缺失的演变是肝硬化[风险比（HR）：1.52，95%置信区间（CI）1.02 - 2.25]和HCC（HR：4.0，95%CI 1.6 - 10.1）的独立预测因素。
HBeAg阳性状态下前S区缺失和T1762/A1764的联合存在及演变是自发HBeAg血清学转换患者临床结局的一个显著预测因素。
