Li Xiaodong, Qin Yaqun, Liu Yan, Li Fan, Liao Hao, Lu Shanshan, Qiao Yan, Xu Dongping, Li Jin
Research Center for Clinical and Translational Medicine, Beijing 302 Hospital, Beijing 100039, China.
The Second Liver Cirrhosis Medical Center, Beijing 302 Hospital, Beijing 100039, China.
J Clin Virol. 2016 Sep;82:27-32. doi: 10.1016/j.jcv.2016.06.018. Epub 2016 Jun 29.
The association of hepatitis B virus (HBV) preS1 and preS2 deletions with progressive liver diseases are not fully understood.
The study aimed to investigate characteristics of HBV preS deletion in HBV-infected patients with different illness categories.
Total of 539 HBV-infected patients were enrolled in the study, including 146 with chronic hepatitis B (CHB), 111 with HBV-related liver cirrhosis (LC), 146 with HBV-related acute-on-chronic liver failure (ACLF), and 136 with HBV-related hepatocellular carcinoma (HCC). PreS deletion was determined by sequencing. Replicons containing representative preS1 and preS2 deletion mutants and wild-type were respectively constructed and transfected into HepG2 cells for phenotypic analysis.
The detection rates of overall preS deletion were 15.8%, 26.1%, 24.0%, and 34.6% in CHB, LC, ACLF, and HCC patients, respectively. PreS1 deletion was most frequently detected in LC patients while preS2 deletion was most frequently detected in HCC patients, both frequencies were significantly higher than that in CHB patients (17.1% vs. 4.8%, P<0.01; 19.1% vs. 4.8%, P<0.01). The deletion patterns across preS gene were different among the 4 illness categories. Compared with wild-type strain, the preS1 deletion mutant had defected preS1 expression, significantly decreased viral mRNA level and SP II promoter activity; while preS2 deletion mutant had defected preS2 expression, and significantly decreased viral mRNA level.
HBV preS deletion was associated with advancement of liver diseases not only presented in preS deletion incidence, but also in the deletion pattern. Patients with preS2 deletion might have a higher risk to develop HCC.
乙型肝炎病毒（HBV）前S1和前S2缺失与进行性肝病之间的关联尚未完全明确。
本研究旨在调查不同疾病类型的HBV感染患者中HBV前S缺失的特征。
共有539例HBV感染患者纳入本研究，其中慢性乙型肝炎（CHB）患者146例、HBV相关肝硬化（LC）患者111例、HBV相关慢加急性肝衰竭（ACLF）患者146例、HBV相关肝细胞癌（HCC）患者136例。通过测序确定前S缺失情况。分别构建含有代表性前S1和前S2缺失突变体及野生型的复制子，并转染至HepG2细胞进行表型分析。
CHB、LC、ACLF和HCC患者中前S缺失的总体检出率分别为15.8%、26.1%、24.0%和34.6%。前S1缺失在LC患者中最常被检测到，而前S2缺失在HCC患者中最常被检测到，两者的频率均显著高于CHB患者（17.1%对4.8%，P<0.01；19.1%对4.8%，P<0.01）。4种疾病类型中前S基因的缺失模式不同。与野生型毒株相比，前S1缺失突变体的前S1表达缺陷，病毒mRNA水平和SP II启动子活性显著降低；而前S2缺失突变体的前S2表达缺陷，病毒mRNA水平显著降低。
HBV前S缺失不仅在前S缺失发生率上，而且在缺失模式上均与肝病进展相关。前S2缺失的患者可能有更高的发生HCC的风险。
