Department of Infectious Diseases, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Department of Gastroenterology, University Medical Center, Ho Chi Minh City, Vietnam.
PLoS One. 2022 Apr 7;17(4):e0266134. doi: 10.1371/journal.pone.0266134. eCollection 2022.
Chronic hepatitis B virus (CHB) infection is a major health problem and leading cause of hepatocellular carcinoma (HCC) worldwide. Several point and deletion mutations on the PreS/S gene have been intensively considered associated with HCC. This study aimed to describe the characteristics of HBV PreS/S mutations in Vietnamese CHB-infected patients and their association with HCC.
This cross-sectional study was conducted from 02/2020 to 03/2021, recruited Vietnamese CHB-infected patients with HBV-DNA >3 log10-copies/mL and successful PreS/S gene sequencing. Mutations were detected by direct Sanger sequencing.
247 CHB-infected patients were recruited, characterized by 68.8% males, 54.7% HBV genotype B, 57.5% HBeAg positive, 23.1% fibrosis score ≥F3 and 19.8% HCC. 61.8% amino acid replacements were detected throughout the PreS1/PreS2/S genes. The most common point-mutations included N/H51Y/T/S/Q/P (30.4%), V68T/S/I (44.9%), T/N87S/T/P (46.2%) on PreS1 gene; T125S/N/P (30.8%), I150T (42.5%) on PreS2 gene; S53L (37.7%), A184V/G (39.3%), S210K/N/R/S (39.3%) on S gene. The rates of case(s) with any point-mutation on the Major Hydrophylic Region (MHR) and the "a" determinant region were 63.6% and 39.7%, respectively. Most of S point-mutations were presented with low rates such as T47A/E/V/K (9.3%), P120S/T (8.5%), G145R (2%). On multivariable analysis, males (OR = 4.51, 95%CI 1.78-11.4, p = 0.001), age≥40 (OR = 5.5, 95%CI 2.06-14.68, p = 0.001), W4P/R/Y on PreS1 (OR = 11.56, 95%CI 1.99-67.05, p = 0.006) and 4 S point-mutations as: T47A/E/V/K (OR = 3.67, 95%CI 1.19-11.29, p = 0.023), P120S/T (OR = 3.38, 95%CI 1.09-10.49, p = 0.035), S174N (OR = 29.73, 95%CI 2.12-417.07, p = 0.012), P203R (OR = 8.45, 95%CI 1.43-50.06, p = 0.019) were associated with HCC.
We detected 61% amino acid changes on PreS/S regions in Vietnamese CHB patients. One point-mutation at amino acid 4 on PreS1 gene and 4 point-mutations at amino acids 47, 120, 174, and 203 on S gene were associated with HCC. Further investigations are recommended to further clarify the relationship and interaction between mutations in HBV genome and HCC progression.
慢性乙型肝炎病毒（CHB）感染是一个主要的健康问题，也是全球肝细胞癌（HCC）的主要病因。在 PreS/S 基因上的几个点突变和缺失突变已被深入研究与 HCC 相关。本研究旨在描述越南 CHB 感染患者 HBV PreS/S 突变的特征及其与 HCC 的关系。
本横断面研究于 2020 年 2 月至 2021 年 3 月进行，招募了 HBV-DNA >3 log10-copies/mL 且 PreS/S 基因测序成功的越南 CHB 感染患者。突变通过直接 Sanger 测序检测。
共招募了 247 名 CHB 感染患者，男性占 68.8%，HBV 基因型 B 占 54.7%，HBeAg 阳性占 57.5%，纤维化评分≥F3 占 23.1%，HCC 占 19.8%。在整个 PreS1/PreS2/S 基因中检测到 61.8%的氨基酸替换。最常见的点突变包括 N/H51Y/T/S/Q/P（30.4%）、V68T/S/I（44.9%）、T/N87S/T/P（46.2%）在 PreS1 基因上；T125S/N/P（30.8%）、I150T（42.5%）在 PreS2 基因上；S53L（37.7%）、A184V/G（39.3%）、S210K/N/R/S（39.3%）在 S 基因上。在主要亲水区域（MHR）和“a”决定区有任何点突变的病例比例分别为 63.6%和 39.7%。大多数 S 点突变的发生率较低，如 T47A/E/V/K（9.3%）、P120S/T（8.5%）、G145R（2%）。多变量分析显示，男性（OR=4.51，95%CI 1.78-11.4，p=0.001）、年龄≥40 岁（OR=5.5，95%CI 2.06-14.68，p=0.001）、PreS1 上的 W4P/R/Y（OR=11.56，95%CI 1.99-67.05，p=0.006）和 4 个 S 点突变，即：T47A/E/V/K（OR=3.67，95%CI 1.19-11.29，p=0.023）、P120S/T（OR=3.38，95%CI 1.09-10.49，p=0.035）、S174N（OR=29.73，95%CI 2.12-417.07，p=0.012）、P203R（OR=8.45，95%CI 1.43-50.06，p=0.019）与 HCC 相关。
我们在越南 CHB 患者的 PreS/S 区检测到 61%的氨基酸变化。PreS1 基因上的第 4 位氨基酸点突变和 S 基因上的第 47、120、174 和 203 位氨基酸的 4 个点突变与 HCC 相关。建议进一步研究以进一步阐明 HBV 基因组突变与 HCC 进展之间的关系和相互作用。
