摘要
目的 比较不同病程阶段的慢性肝病患者HBV反转录酶区(RT)预存变异的情况。方法 收集2011年1月至2013年6月浙江省上虞市人民医院和浙江大学医学院附属第一医院收治的慢性肝病患者474例,其中慢性乙型肝炎(CHB)组205例,肝硬化组153例和肝癌组116例,所有患者均未接受过核苷(酸)类药物抗病毒治疗。采用PCR后直接测序法检测HBV RT区变异,同时确定基因型。应用SPSS 14.0软件进行统计学分析。结果 患者以HBV基因B型为主,共387例(81.6％),其中CHB组156例,肝硬化组124例,肝癌组107例。387例B基因型患者均存在核苷(酸)类药物耐药变异位点,HBV RT区rtS106C变异阳性率在CHB组(14.1％,22/156)和肝硬化组(14.5％,18/124)高于肝癌组(4.7％,5/107)患者(x2=6.126和6.207,P值均＜0.05);rtD134E/G/N/S变异阳性率在CHB组(21.8％,34/156)和肝硬化组(20.2％,25/124)高于肝癌组(10.3％,11/107)(x2=5.933和4.263,P值均＜0.05)。HBV RT区rtD134E/G/N/S和rtS106C变异与HBeAg和性别有一定的关系,而与HBV DNA载量和年龄无关。CHB组(5.3％,157/2964)和肝硬化组(5.6％,132/2356)的HBV RT区A-B间域的变异频率高于肝癌组(3.5％,71/2033)(x2=9.018和11.018,P值均＜0.01)。结论 未接受核苷(酸)类药物抗病毒治疗的不同阶段慢性肝病患者均可能存在核苷(酸)类药物耐药相关变异。HBV RT区rtS106C和rtD 134E/G/N/S变异可能与不同阶段慢性肝病中严重免疫应答引起的活动性炎症坏死有关。HBV RT区的A-B间域变异可能与炎症坏死、免疫反应和肝纤维化进展有关。
Objective To compare the pre-existing mutations in reverse transcription region of HBV in patients with different HBV infection stages.Methods Totally 474 patients with chronic HBV infections,including 205 with chronic hepatitis B (CHB),153 with liver cirrhosis and 116 with hepatocellular carcinoma (HCC),were enrolled from the People' s Hospital of Shangyu and the First Affiliated Hospital of Zhejiang University during January 2011 and June 2013.All patients had not received nucleos (t)ide analogues treatment.HBV RT region mutations and genotypes were determined by PCR followed by sequencing.SPSS14.0 was used for statistical analysis.Results There were 387 (81.6％) patients with HBV genotype B,in which 156 were with CHB,124 were with liver cirrhosis,and 107 were with HCC.Nucleos(t)ide analogues-related mutations were observed in all the above 387 patients.rtS106C mutation was more popular in CHB and liver cirrhosis (14.1％ and 14.5％) patients than that in patients with HCC (4.7％) (x2 =6.126,6.207,P ＜0.05); And the positive rates of rtD134E/G/N/S mutations were also higher in CHB and cirrhotic patients (21.8％ and 20.2％) than that in HCC patients (10.3％,x2 =5.933,4.263,P ＜ 0.05).rtD134E/G/N/S and rtS106C mutations were correlated with HBeAg (P ＜0.01) and gender (P ＜ 0.05),but not with HBV virus load and age (P ＞ 0.05).The mutation frequencies in A-B interdomain were higher in CHB and cirrhotic patients (5.3％ and 5.6％) than that in HCC patients (3.5％,x2 =9.018,11.018,P ＜ 0.01).Conclusions Nucleos (t) ide analogues-related mutations exist in various HBV infection stages.rtSl06C and rtD134E/G/N/S mutations may be involved in necro-inflammation,and A-B interdomain mutations may be correlated with necro-inflammation,immune response and fibrosis in chronic liver diseases.
出处
《中华临床感染病杂志》
CAS
2013年第5期257-262,共6页
Chinese Journal of Clinical Infectious Diseases
