摘要
目的探讨慢性HBV相关肝病患者HBV基因型和耐药突变位点检测与疾病进展的关系。方法选取230例经核苷(酸)类似物(NAs)治疗的慢性HBV相关肝病患者作为研究对象,检测其外周血HBV基因型和RT区氨基酸序列耐药突变情况。结果 230例慢性HBV相关肝病患者中100例(43.47%)检出NAs耐药突变,以LAM/LdT耐药最多见(30.00%,69/230)、ADV耐药次之(7.83%,18/230)、ETV耐药最少(5.65%,13/230),比较差异有统计学意义(χ^(2)=67.392,P<0.01)。在LAM/LdT耐药中,单点耐药55例(79.71%),以rtM204V/I突变多见(17.39%,40/230);多点耐药14例(20.29%),以rtL180M+rtM204V/I突变多见(5.65%,13/230)。在ADV耐药中,以单点耐药为主(11例,占61.11%),rtA181T是其主要突变位点(3.91%,9/230)。在ETV耐药中,均为多点耐药,以rtM204V/I+rtA181T+rtS202G/I突变为主(突变率为3.04%,7/230)。230例慢性HBV相关肝病患者均为B基因型和C基因型,未检测到A、D、E、F、G、H、J基因型,其中B基因型患者162例(70.43%);C基因型患者68例(29.57%)。HBV B基因型和C基因型在rt180突变率和rt181突变率上比较,差异均有统计学意义(χ^(2)=11.545、4.845,均P<0.05),但在其他位点突变上差异无统计学意义(P>0.05)。慢性乙型肝炎组、乙型肝炎相关肝硬化组HBV基因型分布差异有统计学意义(χ^(2)=25.012,P<0.01)。慢性乙型肝炎组、乙型肝炎相关肝硬化组和乙型肝炎相关肝癌组rt204耐药位点突变率比较,差异有统计学意义(P=0.015),但其他位点突变率差异无统计学意义(P>0.05)。结论本地区慢性HBV相关肝病患者基因型以B型和C型为主,NAs主要耐药突变点检出率较高,其中不同基因型疾病进展情况和耐药突变情况存在差异,而在不同疾病阶段rt204耐药位点突变率亦存在差异。
Objective To explore the relationship of hepatitis B virus(HBV)genotypes and drug resistance mutation sites to disease progression in patients with HBV-related chronic liver diseases.Methods Two hundred and thirty patients with HBV-related chronic liver diseases treated with nucleos(t)ide analogues(NAs)were selected as study subjects.HBV genotypes and drug-resistant mutations within reverse transcriptase(RT)region were detected.Results Among the 230 patients with HBV-related chronic liver disease,100 cases(43.47%)were found to have NA-resistant mutations,with lamivudine(LAM)/telbivudine(LdT)resistance being the most common(30.00%,69/230),adefovir(ADV)resistance being the second(7.83%,18/230),entecavir(ETV)resistance being the least(5.65%,13/230),and there was statistically significant difference among them (χ^(2)=67.392,P<0.001).Among the cases with LAM/LdT-resistant mutations,55 were single-point mutant(79.71%),most being rtM204V/I mutations(17.39%,40/230);14 were multipoint mutant(20.29%),most being rtL180M+rtM204V/I mutations(5.65%,13/230).Among the cases of ADV resistant mutations,most were single-point mutant(61.11%,11/18),Rta181 t mutations being the most prevalent(3.91%,9/230).And all cases of ETV-resistant mutations were multi-point mutant,most being rtm204 v/I+rta181 t+rts202 g/I mutations(3.04%,7/230).In all the patients with HBV-related chronic liver diseases,HBV genotypes were B(70.43%,162/230)and C(29.57%,68/230),with no genotype A,D,E,F,G,H or J.There was significant difference in mutation rates of rt180 and rt181 between genotype B and C of HBV (χ^(2)=11.545,P=0.001;χ^(2)=4.845,P=0.028),no significant difference in rates of other mutations(P>0.05).The distribution of HBV genotypes was statistically different between chronic hepatitis B group and hepatitis B-related cirrhosis group (χ^(2)=25.012,P<0.001).The rate of rt204 mutation was significantly different among chronic hepatitis B group,hepatitis B-related cirrhosis group and hepatitis B-related liver cancer group(P=0.015),and rates of other
作者
刘理冠
叶巧霞
严彦
颜燕燕
黄志杰
张小曼
LIU Li-guan;YE Qiao-xia;YAN Yan;YAN Yan-yan;HUANG Zhi-jie;ZHANG Xiao-man(Department of Infectious Diseases,the 910h Hospital of The Joint Service Support Force of People's Liberation Army,Quanzhou362000,China)
出处
《肝脏》
2021年第3期287-290,共4页
Chinese Hepatology
基金
2018年泉州市科技计划项目(2018N135S)。
关键词
慢性HBV相关肝病
HBV基因型
核苷(酸)类似物
耐药突变
疾病进展
Hepatitis B virus-related chronic liver disease
Hepatitis B virus genotype
Nucleos(t)ide analogue
Drug resistance mutation
Disease progression
