摘要
目的研究HBV逆转录酶区(reverse transcriptase,RT)自然变异情况,分析与不同阶段慢性肝病的关系。方法收集年龄和性别比例相匹配的三组患者(未接受抗病毒治疗):慢性乙型肝炎227例,肝硬化167例和肝癌121例,采用PCR后直接测序法检测HBV逆转录酶区变异,同时确定基因型。结果患者以HBV基因B型为主,分析全部418例B型患者(慢乙肝,173例;肝硬化,135例;肝癌,110例),发现了核苷(酸)类似物(Nucleos(t)ide analogue,NA)相关耐药变异(rtL80I/V,rtI169T,rtV173L,rtL180M,rtA181T,rtS202C,rtM204I/V,rtN236T);HBV逆转录酶区rtS106C变异在慢乙肝和肝硬化组患者中的阳性率(13.3%和14.8%)高于肝癌组(5.5%)患者(χ2=4.494,P=0.034和χ2=5.598,P=0.018);rtD134E/G/N/S变异在慢乙肝和肝硬化组患者中的阳性率(21.4%和20.7%)高于肝癌组(10.0%)患者(χ2=6.191,P=0.013和χ2=5.224,P=0.022);HBV逆转录酶区A-B间域的变异频率在慢乙肝和肝硬化组患者中(5.4%和6.0%)高于肝癌组(3.4%)患者(χ2=11.188,P=0.001和χ2=16.325,P<0.001)。结论不同阶段慢性HBV感染者(未接受抗病毒治疗)确实存在核苷(酸)类似物耐药相关变异。HBV逆转录酶区的rtS106C变异、rtD134E/G/N/S变异和A-B间域变异可能与慢性肝病的炎症坏死、免疫反应和纤维化进展有关。
Objective To characterize the profiles of naturally occurring mutations in the HBV RT region and their related clinical outcomes.Methods The serum samples of untreated HBV patients were collected includ in chronic hepatitis B patients（227 cases）,cirrhotic patients（167 cases） and hepatocellular carcinoma patients（121 cases）.HBV RT region mutations and genotypes were determined by PCR-direct sequencing.Results The HBV genotype of most cases was genotype B,and all of the genotype B cases were analyzed（173 chronic hepatitis B patients,135 cirrhotic patients and 110 hepatocellular carcinoma patients）.The nucleos（t）ide analogues related mutations（rtL80I/V,rtI169T,rtV173L,rtL180M,rtA181T,rtS202C,rtM204I/V,rtN236T） were found.The rtS106C mutation was higher in chronic hepatitis B and cirrhotic patients（13.3% and 14.8%） than that in hepatocellular carcinoma（5.5%） patients（χ2=4.494,P=0.034 and χ2=5.598,P= 0.018,respectively）.And the rtD134E/G/N/S mutations were also higher in chronic hepatitis B and cirrhotic patients（21.4% and 20.7%） than that in hepatocellular carcinomapatients（（10.0%）,χ2=6.191,P=0.013 and χ2=5.224,P=0.022,respectively）.The mutation frequencies in A–B interdomain were higher in chronic hepatitis B and cirrhotic patients（5.4% and 6.0%） than that in hepatocellular carcinoma patients,（（3.4%,χ2=11.188,P=0.001 andχ2=16.325,P0.001,respectively）.Conclusions The nucleotide analogues related mutations do exist in treatment naive patients with different disease stages.The rtS106C,rtD134E/G/N/S and A–B interdomain mutations may be associated with necro-inflammation,immune response and fibrosis development of chronic liver diseases.
出处
《中国热带医学》
CAS
2013年第6期738-742,共5页
China Tropical Medicine
关键词
乙型肝炎病毒
逆转录酶区
变异
初治
临床结局
Hepatitis B virus
Reverse transcriptase
Mutations
Naive
Clinical outcomes.
