HBV基因BCP区1762/1764和前C区1896突变与GGT/ALT联合分析对HBV-HCC的早期诊断价值研究

Study on early diagnostic value of combined analysis of hepatitis B virus gene basal core promoter region 1762/1764 and pre-core region 1896 mutation with GGT/ALT in hepatitis B virus related hepatocellular carcinoma

目的探讨乙型肝炎病毒(HBV)基因核心启动子(BCP)区1762/1764和前C区1896基因突变与血清γ-谷氨酰转移酶(GGT)及丙氨酸氨基转移酶(ALT)联合分析对HBV相关性肝细胞癌(HBV-HCC)的诊断价值。方法收集2015年9月至2018年6月经该院确诊(HBV DNA≥1000 IU/mL)的HBV相关疾病患者159例,其中慢性乙型肝炎(CHB)63例,肝硬化50例,HBV-HCC 46例;比较各组患者GGT与ALT水平;采用扩增阻滞突变系统荧光PCR(ARMS-PCR)法检测HBV基因BCP区1762/1764和前C区1896突变。结果HBV-HCC组患者的血清GGT水平和GGT/ALT比值均高于肝硬化组和CHB组,差异均有统计学意义(P<0.01)。HBV-HCC组、肝硬化组、CHB组的HBV基因BCP区1762/1764突变率分别为91.30%、84.00%、22.22%,HBV-HCC组与CHB组比较差异有统计学意义(P<0.05),而HBV-HCC组与肝硬化组比较差异无统计学意义(P>0.05);HBV基因前C区1896突变率分别为84.78%、64.00%、39.68%,HBV-HCC组与CHB组和肝硬化组比较差异均有统计学意义(P<0.05)。HBV基因BCP区1762/1764突变型与未突变型和前C区1896突变型与未突变型的GGT/ALT比值比较,差异均有统计学意义(P<0.05)。诊断HBV-HCC的受试者工作特征(ROC)曲线分析结果显示,BCP区1762/1764突变检测联合GGT/ALT比值时,诊断灵敏度为71.70%、特异度为83.20%;前C区1896突变检测联合GGT/ALT比值时,诊断灵敏度为87.00%、特异度73.50%;BCP区和前C区突变检测联合GGT/ALT比值时,诊断灵敏度为93.50%、特异度为74.30%。结论HBV基因BCP区1762/1764突变、前C区1896突变和GGT/ALT比值均与HBV-HCC发生相关,三者联合分析对HBV-HCC的早期诊断具有临床应用价值。

Objective To explore the diagnostic value of combined analysis of hepatitis B virus(HBV)gene basal core promoter(BCP)region 1762/1764 and pre-core(PC)region 1896 gene mutations with the GGT/ALT in hepatitis B virus related hepatocellular carcinoma(HBV-HCC).Methods A total of 159 cases of hepatitis B related disease(HBV DNA levels≥1000 IU/mL)in this hospital from September 2015 to June 2018 were collected,including 63 cases of chronic hepatitis B(CHB),50 cases of liver cirrhosis(LC)and 46 cases of HBV-HCC.The levels of GGT and ALT were compared among the various groups.HBV gene BCP region 1762/764 and PC region 1896 mutations were determined by ARMS-PCR.Results The serum GGT level and GGT/ALT ratio in the HBV-HCC group were higher than those in the LC group and CHB group,the differences were statistically significant(P<0.01).The mutation rates of the HBV gene BCP1762/1764 in the HBV-HCC,LC and CHB groups were 91.30%,84.00%and 22.22%respectively,the differences between HBV-HCC group and CHB group were statistically significant(P<0.05),while which between the HBV-HCC group and LC group showed no statistical significance(P>0.05).The mutation rates of the HBV gene PC region 1896 in the HBV-HCC,LC and CHB groups were 84.78%,64.00%,39.68%respectively,the difference between HBV-HCC and CHB were statistically significant(P<0.05).The GGT/ALT ratio mean values showed statistically significant differences between the HBV gene BCP1762/1764 mutant types and non-mutant types and between the PC region 1896 mutation types and non-mutation type(P<0.05).The ROC curve analysis for the diagnosis of HBV-HCC showed that the sensitivity in the combined detection of BCP172/1764 mutations and the GGT/ALT ratio was 71.70%and its specificity was 83.20%;the sensitivity and specificity in the combine detection of PC 1896 mutations and the GGT/ALT ratio were 87.00%and 73.50%respectively;which in the combined detection of BCP172/1764 mutations,PC 1896 mutations and the GGT/ALT ratio were 93.50%and 74.30%respectively.Conclusion HBV gene BCP 1762/1764 mutations,PC region 1896 mutations and GGT/ALT ratio all are related to the HBV-HCC occurrence and their combined analysis has the clinical application value for early diagnosing HBV-HCC.