慢性HBV感染者不同病程阶段HBV前S基因缺失突变的比较分析  

Comparative analysis of HBV pre-S deletion in chronically HBV-infected patients with different illness categories

作　　者：秦雅群 李晓东[2] 廖昊 李梵[2] 卢珊珊[2] 刘妍[2] 徐东平[2] 李进[3] 

机构地区：[1]广西桂林医学院,541004 [2]解放军第三〇二医院肝衰竭诊疗与研究中心,北京100039 [3]解放军第三〇二医院

出　　处：《传染病信息》2015年第2期79-82,共4页Infectious Disease Information

基　　金：国家自然科学基金(81373136;81271847)

摘　　要：目的探讨慢性HBV感染者不同病程阶段前S(pre-S)基因缺失的临床流行特点及其临床意义。方法采用巢式PCR方法扩增测序146例慢性乙型肝炎(chronic hepatitis B,CHB)患者(CHB组)、111例HBV相关肝硬化(liver cirrhosis,LC)患者(LC组)、146例慢加急性肝衰竭(acute-on-chronic liver failure,ACLF)患者(ACLF组)和136例HBV相关肝细胞癌(hepatocellular carcinoma,HCC)患者(HCC组)的HBV pre-S基因(nt 2848-154)。分析比较不同组pre-S基因缺失发生率、缺失热点区域和缺失片段长度。结果 LC组和HCC组HBV pre-S基因缺失率显著高于CHB组(26.1%vs.15.8%,P=0.040;34.6%vs.15.8%,P<0.001);LC组pre-S1基因单独缺失率显著高于CHB组(17.1%vs.4.8%,P=0.001);HCC组pre-S2基因单独缺失率显著高于CHB组(19.1%vs.4.8%,P<0.001)。不同病程阶段患者发生缺失的热点区域也不相同,CHB组发生缺失的热点区域为nt 3031-3215(30.4%)和nt 24-57(30.4%);LC组为nt 2849-2866(55.2%)和nt 5-55(31.0%);ACLF组为nt 2849-2866(28.6%)和nt 1-54(25.7%);HCC组为nt 5-55(57.4%)和nt 2849-2866(12.8%)。不同病程阶段患者发生pre-S基因缺失的片段长度差异无统计学意义。结论慢性HBV感染者中,随着疾病进展HBV pre-S基因缺失率呈上升趋势,其中pre-S1基因缺失突变在LC患者中显著增高,pre-S2基因缺失突变在HCC患者中显著增高。pre-S基因缺失可能参与驱动HBV慢性感染的疾病进展。Objective To investigate the clinical and epidemiological characteristics of pre-S deletion in chronically HBV- infected patients with different illness categories. Methods pre-S gene （nt 2848-154） from 146 patients with chronic hepatitis B （CHB） （CHB group）, 111 patients with liver cirrhosis （LC） （LC group）, 146 patients with acute-on-chronic liver failure （ACLF） （ACLF group） and 136 patients with hepatocellular carcinoma （HCC） （HCC group） were amplified by nested PCR and sequenced. Comparative analysis was performed on the occurrence rate, hotspot and fragment length of pre-S deletion mutation of the 4 different groups. Results Among the 4 groups, the overall pre-S deletion mutation rates of LC group and HCC group were significantly higher than that of CHB group （26.1% vs. 15.8%, P=0.040; 34.6% vs. 15.8%, P〈0.001）; pre-S1 deletion mutation rate of LC group was significantly higher than that of CHB group （17.1% vs. 4.8%, P=0.001）; pre-S2 deletion mutation rate of HCC group was significantly higher than that of CHB group （19.1% vs. 4.8%, P〈O.O01）. The hotspots of deletions varied in different groups, nt 3031-3215 （30.4%） and nt 24-57 （30.4%） in CHB group, nt 2849-2866 （55.2%） and nt 5-55 （31.0%） in LC group, nt 2849-2866 （28.6%） and nt 1-54 （25.7%） in ACLF group, and nt 5-55 （57.4%） and nt 2849-2866 （12.8%） in HCC group. There were no significant differences in deletion fragment length among the 4 groups. Conclusions Among the patients with chronic HBV infection, the overall pre-S deletion mutation rates increase with the disease progression. The pre-S1 deletion mutation rate significantly increases in LC patients, while the pre-S2 deletion mutation rate significantly increases in HCC patients. HBV pre-S deletion may be a driving factor for the progression of chronic HBV infection.

关 键 词：乙型肝炎病毒 序列缺失 抗原 表面 乙型肝炎 慢性 肝硬化 癌 肝细胞 

分 类 号：R512.62[医药卫生—内科学]