Lee Danbi, Lyu Heather, Chung Young-Hwa, Kim Jeong A, Mathews Priya, Jaffee Elizabeth, Zheng Lei, Yu Eunsil, Lee Young Joo, Ryu Soo Hyung
Danbi Lee, Young-Hwa Chung, Jeong A Kim, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea.
World J Gastroenterol. 2016 Jun 21;22(23):5393-9. doi: 10.3748/wjg.v22.i23.5393.
To determine the genomic changes in hepatitis B virus (HBV) and evaluate their role in the development of hepatocellular carcinoma (HCC) in patients chronically infected with genotype C HBV.
Two hundred and forty chronic hepatitis B (CHB) patients were subjected and followed for a median of 105 mo. HCC was diagnosed in accordance with AASLD guidelines. The whole X, S, basal core promoter (BCP), and precore regions of HBV were sequenced using the direct sequencing method.
All of the subjects were infected with genotype C HBV. Out of 240 CHB patients, 25 (10%) had C1653T and 33 (14%) had T1753V mutation in X region; 157 (65%) had A1762T/G1764A mutations in BCP region, 50 (21%) had G1896A mutation in precore region and 67 (28%) had pre-S deletions. HCC occurred in 6 patients (3%). The prevalence of T1753V mutation was significantly higher in patients who developed HCC than in those without HCC. The cumulative occurrence rates of HCC were 5% and 19% at 10 and 15 years, respectively, in patients with T1753V mutant, which were significantly higher than 1% and 1% in those with wild type HBV (P < 0.001).
The presence of T1753V mutation in HBV X-gene significantly increases the risk of HCC development in patients chronically infected with genotype C HBV.
确定乙型肝炎病毒(HBV)的基因组变化,并评估其在慢性感染C基因型HBV患者肝细胞癌(HCC)发生中的作用。
对240例慢性乙型肝炎(CHB)患者进行研究并随访,中位随访时间为105个月。根据美国肝病研究学会(AASLD)指南诊断HCC。采用直接测序法对HBV的整个X、S、核心启动子(BCP)和前核心区进行测序。
所有受试者均感染C基因型HBV。在240例CHB患者中,25例(10%)X区域有C1653T突变,33例(14%)有T1753V突变;157例(65%)BCP区域有A1762T/G1764A突变,50例(21%)前核心区有G1896A突变,67例(28%)有前S区缺失。6例患者(3%)发生了HCC。发生HCC的患者中T1753V突变的发生率显著高于未发生HCC的患者。T/T1753V突变患者在10年和15年时HCC的累积发生率分别为5%和19%,显著高于野生型HBV患者的1%和1%(P<0.001)。
HBV X基因中T1753V突变的存在显著增加了慢性感染C基因型HBV患者发生HCC的风险。