C基因型乙型肝炎病毒前C区及基本核心启动子突变与疾病进展的相关性研究

Association between HBV precore and basal core promoter mutations with progress of liver disease in patients with chronic HBV infection

目的探讨HBV前C区(PreC)及基本核心启动子(BCP)突变与慢性乙型肝炎病毒(HBV)感染者疾病进展的关系。方法收集88例慢性HBV感染者血清标本,包括36例无症状携带者(其中24例为HBV携带者,12例为HBsAg携带者)、36例慢性乙型肝炎(慢性乙肝)和16例肝硬化患者。所有标本均经型特异性引物PCR法鉴定为HBV C基因型,并用巢氏PCR法扩增HBV PreC和BCP基因片段,用PCR产物直接测序法测序,然后用Clustal W1.8软件进行序列分析。结果在50例HBeAg阳性患者中,无症状携带者、慢性乙肝和肝硬化组的T1762/A1764双突变率和T1846突变率分别为12.5%、42.1%、100%和0%、5.3%、28.6%,差异均有统计学意义(P值分别为0.03和0.02)。在38例HBeAg阴性HBV感染者中,无症状携带者、慢性乙肝和肝硬化组的T1762/A1764双突变率分别为16.7%、58.8%和66.7%,差异无统计学意义(P=0.08)。肝硬化组的C/G1753突变率显著高于无症状携带者及慢性乙肝组(分别为55.6%、8.3%、11.8%,P=0.01),其A1896突变率也高于无症状携带者组(分别为55.6%、8.3%,P=0.01)。结论HBV T1762/A1764双突变与C基因型HBV慢性感染者的疾病进展有关。

Objective To investigate the association between HBV precore （PreC）/basal core promoter （BCP） mutations with the progress of liver disease in patients with chronic HBV infection. Methods Eighty-eitht patients with genotype C HBV infection were enrolled, including 36 asymptomafic carriers, 36 chronic hepatitis and 16 cirrhosis patients. C, enotypes were determined by a type-specific primer PCR. PreC/BCP regions of HBV were amplified by nested PCR and sequenced directly. Mutations in PreCJBCP regions were determined by alignment of all sequence using software of Clnstal W1.8. Results In 50 HBeAg-positive patients, frequencies of T1762/ A1764 and T1846 mutations in groups of asymptomatic carriers, chronic hepatitis B and liver cirrhosis were 12.5%, 42.1% and 100%, 0%, 5.3% and 28.6%, respectively, with significant differences among these three groups （P = 0.03 and P = 0.02, respectively）. Among 38 HBeAg-negative patients, T1762/A1764 muta- tion frequencies of asymptomatic carriers, patients with chronic hepatitis B and liver cirrhosis were 16.7%, 58.8 % and 66.7 %, respectively （ P = 0.08）. The group of patients with liver cirrhosis had a significantly higher frequency of C/G1753 mutation than that of asymptomatic carrier and chronic hepatitis B groups （55.6% vs 8.3% and 55.6% vs 11.8%, P = 0.01）. The frequency of A1896 mutation in the liver cirrhosis group was also signifi- cantly higher than that of the asymptomatic carrier group （8.3% vs 55.6%, P = 0.01 ）. Conclusion T1762/ A1764 mutations may be associated with progression of the genotype C HBV related liver disease.