乙型肝炎病毒前核心区及基本核心启动子变异的检测及其对患者疾病谱的影响

目的探讨乙型肝炎病毒(HBV)前核心区(前C区,nt1896)及基本核心启动子(BCP,nt1762/1764)变异在慢性HBV感染者疾病谱的分布及对患者疾病谱的影响。方法416例血清HBsAg阳性、HBVDNA定量大于1.0×104拷贝/毫升的患者,采用微流基因芯片检测HBV前C区及BCP变异。结果416例HBV感染者中302例为HBeAg(-)患者,其中248例(82.12%)有前C区或BCP变异,41.06%为前C区变异,31.12%BCP变异,2种同时变异为9.94%。HBeAg(-)的慢性乙型肝炎和肝硬化患者前C区变异分别为64.72%和83.33%(x2=0.89,P>0.05),均大于HBeAg(-)无症状携带者的28.47%(x2=54.20,P<0.01;x2=5.29,P<0.05);而HBeAg(-)无症状携带者BCP变异达77.19%,大于HBeAg(-)慢性乙型肝炎和肝硬化患者(x2=69.73,P<0.01;x2=10.58,P<0.01)。而在114例HBeAg(+)患者中28.95%有前C区或BCP变异。结论前C区或BCP变异在慢性HBV感染者疾病谱的分布不同,在HBeAg(-)/HBVDNA(+)与HBeAg(+)/HBVDNA(+)患者变异率差异显著。HBV前C区可能是该病变反复及加重的一个重要原因,但BCP变异临床意义不明确。

Clinical significance of mutations of hepatitis B virus precore and basic core promotor in patients with hepatitis B

ObjectiveTo study the clinical significance of hot spot mutations of hepatitis B virus (HBV)precore and basic core promotor (BCP).MethodsSerum samples of 416 patients with chronic hepatitis B (CHB) were detected by microfluidic chip.Results248 patients (82.12%) had mutations of precore or/and BCP in 302 HBeAg negative cases among 416 patients,in which the rate of patients with precore mutant and with BCP mutant and with double mutants was 41.06%,31.02% and 9.94%,respectively.The precore mutation rate of HBeAg negative patients with CHB and with liver cirrhosis was 64.72% and 83.33%(x~2=0.89,P>0.05),but that of asymptomatic carriers was 28.47%(x~2=54.20,P<0.01;x~2=5.29,P<0.05).The BCP mutation rate of HBeAg negative carriers was 77.19%,greater than that of patients with CHB and with liver cirrhosis(x~2=69.73,P<0.01;x~2=10.58,P<0.01).33(28.95%)patients had mutations of precore or/and BCP in the 114 HBeAg positive cases(x~2=106.2,P<0.01).ConclusionThe significant difference in the frequency of precore or/and BCP mutant was found in patients chronically infected with HBV,especially between HBeAg negative and HBeAg positive patients.The precore mutation of HBV may have a key role in deteriorating and relapsing illness in patients with CHB.The clinical significance of BCP mutation of HBV is not really identified.