Department of Medical Technology, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani, Thailand.
Thammasat University Research Unit in Diagnostic Molecular Biology of Chronic Diseases related to Cancer (DMB-CDC), Thailand.
Asian Pac J Cancer Prev. 2024 Feb 1;25(2):371-377. doi: 10.31557/APJCP.2024.25.2.371.
Chronic hepatitis B (CHB) is well-known as a major risk for liver cirrhosis and hepatocellular carcinoma (HCC). The A1762T/G1764A double mutation in the hepatitis B virus genome affects the production of HBe antigen and is established as a predictive marker for progression to HCC. Thus, this study aimed to investigate the prevalence and clinical significance of the mutation in Thai CHB patients.
A cross-sectional study was conducted in 78 Thai CHB patients who were assessed for hepatitis B profiles, HBsAg, HBeAg and anti-HBeAg, transaminitis, liver fibrosis defined by FIB-4 (FIB-4) score and AST to platelet ratio index (APRI), alpha-fetoprotein (AFP) and active hepatitis B status. HBV A1762T/G1764A mutation was examined by SYBR Green I Real-time PCR. Chi-square and Mann-Whiney U tests were performed to determine the association between the mutation and variables.
The prevalence of patients infected with the A1762T/G1764A mutation was 44.9%. The mutation was associated with HBeAg status (p=0.027) and HBsAg levels (p=0.008), transaminitis (p=0.011), and active hepatitis B (p=0.037), but not liver fibrosis markers, FIB-4 score and APRI, and AFP. Binary logistic regression identified the mutation as a predictive factor of active hepatitis B (OR 3.5, 95%CI, 1.1-11.3, p=0.037). Patients infected with the mutant exhibited significantly higher levels of HBsAg (p=0.011) and HBV viral load (p=0.047), but lower levels of HBeAg (p=0.12) than those infected with the wild-type HBV.
The data indicate the high prevalence of the A1762T/G1764A mutation and its significant association with the severity of Thai CHB patients and the HBV mutation is proposed as a predictive marker of active hepatitis B status in CHB patients.
慢性乙型肝炎(CHB)是肝硬化和肝细胞癌(HCC)的主要危险因素。乙型肝炎病毒基因组中的 A1762T/G1764A 双突变影响 HBe 抗原的产生,并被确立为 HCC 进展的预测标志物。因此,本研究旨在调查泰国 CHB 患者中该突变的流行率和临床意义。
对 78 例泰国 CHB 患者进行横断面研究,评估其乙型肝炎谱、HBsAg、HBeAg 和抗-HBeAg、转氨基酶、FIB-4(FIB-4)评分和天冬氨酸转氨酶与血小板比值指数(APRI)、甲胎蛋白(AFP)和活动性乙型肝炎状态定义的肝纤维化。通过 SYBR Green I 实时 PCR 检测 HBV A1762T/G1764A 突变。采用卡方检验和曼-惠特尼 U 检验确定突变与变量之间的关系。
感染 A1762T/G1764A 突变的患者患病率为 44.9%。该突变与 HBeAg 状态(p=0.027)和 HBsAg 水平(p=0.008)、转氨基酶(p=0.011)和活动性乙型肝炎(p=0.037)相关,但与肝纤维化标志物、FIB-4 评分和 APRI 以及 AFP 无关。二元逻辑回归确定该突变是活动性乙型肝炎的预测因子(OR 3.5,95%CI,1.1-11.3,p=0.037)。感染突变体的患者 HBsAg(p=0.011)和 HBV 病毒载量(p=0.047)水平显著升高,但 HBeAg 水平(p=0.12)较低。
数据表明 A1762T/G1764A 突变的高流行率及其与泰国 CHB 患者严重程度的显著相关性表明,HBV 突变可作为 CHB 患者活动性乙型肝炎状态的预测标志物。