中文摘要：

目的：分析慢性乙型肝炎肝硬化结节样变与 HBV 变异的关系以及 HBV 变异在慢性肝硬化、肝癌进展中的作用。方法收集临床诊断慢性乙型肝炎肝硬化患者104例，其中不典型结节样增生病例43例，单纯肝硬化患者41例，肝癌患者20例。采用荧光探针实时定量 PCR 试剂盒提取 HBV 基因组，选取 PCR 强阳性产物用 Sanger 双脱氧链末端终止法对 HBV 前 C 区变异基因 G1896A ，BCP 区 G1764A、A1762T 位点在全自动核苷酸分析仪上测序，测序结果与 Gene Bank 中 pADR 标准株序列作对比分析。结果结节性增生组、单纯肝硬化组、肝癌组患者 HBV 前 C Gl896A 变异检出率分别是52．3％、40．1％和37．4％，差异无统计学意义（χ2＝0．547，P ＝0．05）；结节性增生组 BCP A l762T 变异率68．4％，与单纯硬化组36．3％比较，差异有统计学意义（P ＝0．038），与肝癌组 G1764A 变异检出率分别是73．0％，与对照组比较具有显著性差异（P ＝0．0411）。单纯肝硬化组、结节性增生组 BCP 基因变异（＋）组，HBV DNA 载量2．18×107、1．2×106高于基因变异（-）组1．18×104、2．95×103，差别有统计学意义（P ＝0．0451，P ＝0．0412）；结节性增生组、肝癌组 BCP 基因变异（＋）组HBeAg 定量750．00 IU／mL，1300．00 IU／mL 高于基因变异（-）组416．13 IU／mL，927．60 IU／mL 差别有统计学意义（P ＝0．0451，P ＝0．0073）。结论前 C 区变异与乙肝肝硬化结节样变临床进展为肝癌无关，而 BCP 区变异与乙肝结节样变临床进展为肝癌有关。

英文摘要：

Objective To analyze the relationship between hepatic dysplastic nodules （HDN）from HBV-related cirrhosis and HBV mutation.Methods One hundred and four cases of clinically diagnosed as HBV-related cirrhosis were enrolled,43 （HDN group）of which had a history of liver cirrhosis （LC）with abdominal ultrasound or CT diagnosis of atypical nodular hyperplasia,41 （LC group ） of which were cirrhosis patients without nodular hyperplasia, and 20 （hepatocellular carcinoma,HCC group）of which were liver cancer patients.HBV genome was exacted by real-time quantitative polymerase chain reaction （PCR）using a fluorescent probe extraction reagent kit.Strong positive PCR product was sequenced with Sanger dideoxy chain termination method to examine HBV mutations on pre-C G1896A and BCP G1764A,A1762T.Sequencing results were compared with pADR standard strain sequence of gene bank.Results The HBV mutation detection rate on pre-C G1896A was 52.3%,40.1 % and 37.4% in HDG,LC and HCC group, respectively,which showed no statistically significant difference （χ2 = 0.547,P =0.05）;there was a significant difference in BCP A1762T mutation rate between HDN and LC group （68.4% versus 36.3%,P =0.038）.Compared with LC group, HCC group had a higher mutation detection rate of 73.0% on G1764A,with significant difference （P =0.0411）.Mutation positive BCP gene was associated with significantly higher HBV DNA loads in LC and HDN group,compared with mutation negative BCP （2.18×107 versus 1 .18 ×104 ,P =0.0451 in LC group,1 .2 ×106 versus 2.95 ×103 ,P =0.0412 in HDN group,respectively）;in addition,mutation positive BCP gene showed statistically higher HBeAg levels than mutation negative BCP gene in HDN and HCC group （750.00 IU/ml versus 416.13 IU/ml,P =0.0451 in HDN group,1300.00 IU/ml versus 927.60 IU/ml,P =0.0073 in HCC group,respectively）.Conclusion BCP mutation was associated with clinical progression of hepatitis B nodular amyloidosis and played a vital role in malignant transformation of hepatitis B nodu