乙型肝炎病毒开放编码区T53C、G912A突变的临床意义

The clinical significance of mutations of T53C, G912A within HBV-DNA open reading frame

目的探讨HBV DNA开放编码区T53C、G912A突变的临床意义。方法 2004-2006年留存血清标本的慢性HBV感染患者112例,其中慢性乙型肝炎(CHB)69例(61.6%),乙肝肝硬化(LC)37例(33.0%),乙肝相关肝癌(HCC)6例(5.4%)。所有血清标本均进行HBV DNA全基因组测序。随访5~7年,将发生LC、HCC、反复肝功能异常或死亡事件定义为疾病进展,探讨乙肝病毒开放编码区突变与疾病进展的关系。结果 S区T53C突变在CHB、LC、HCC组的发生率分别为9.7%、18.8%、25.0%,差异无统计学意义(P=0.269),P区G912A突变在3组的发生率分别为14.3%、28.6%、66.7%,差异有统计学意义(P=0.039)。随访5~7年,T53C在疾病未进展组、进展组的突变发生率分别为7.6%、24.1%,G912A在疾病未进展组、进展组的突变发生率分别为14.6%、36.4%,差异均有统计学意义(P<0.05)。结论 S区T53C、P区G912A可能与乙肝相关肝病的进展有一定相关性。

Objective To investigate the clinical significance of mutations of T53 C, G912 A within HBV-DNA open reading frame（ORF）. Methods The serum samples of 112 chronic HBV-infected patients, who were recruited from 2004 to 2006, were collected. Among them, 69 cases（61.6%） were chronic hepatitis B（CHB）, 37 cases（33.0%） were HBV-related liver cirrhosis（LC）, and 6 cases（5.4%）were HBV-related hepatocellular carcinoma（HCC）. The HBV-DNA sequence was successfully determined. All the patients were followed up for 5 to 7 years, and the progression to LC/HCC/recurrent liver dysfunction/death was defined as the exacerbation of disease. The roles of mutations of HBV-DNA ORF were investigated in the progression of disease. Results The mutation prevalence of G912 A in P region in this study was significantly different between CHB, LC and HCC group（14.3%, 28.6%, 66.7%, P〈0.05）, but that of T53 C in S region was not（9.7%,18.8%, 25.0%, P〈0.05）. After 5 to 7 years, the mutation prevalence of T53 C and G912 A were significantly different between the stable disease group and the progression group（7.6% vs. 24.1%, 14.6% vs. 36.4%, P〈0.05）. Conclusion The mutations of T53 C in S region and G912 A in P region may be related to the progression of HBV related liver disease.