LAM耐药乙肝患者进行LAM联合ADV治疗效果的观察

发布时间：2018-04-15 15:02

本文选题：乙肝病毒 + 拉米夫定　；参考：《河北医科大学》2017年硕士论文

【摘要】：目的:分析石家庄地区454例各种经核苷(酸)类似物治疗的慢性乙型肝炎病例体内乙肝病毒耐药突变的基因位点类型及变异状况,观察使用拉米夫定(LAM)及LAM联合阿德福韦酯(ADV)进行治疗的乙肝患者中P区基因出现突变患者换药后疗效,为提高慢性乙型肝治疗效果提供科学依据方法:1实验研究对象慢性乙型肝炎患者来源于2011年10月-2016年3月石家庄市第五医院就诊的患者,诊断标准依据中华医学会肝病学分会与中华医学会感染病学分会联合制定的《慢性乙型肝炎防治指南(2010年版)进行,筛选均进行核苷类似物的治疗患者。2研究对象分组对筛选出的研究对象均进行乙肝耐药基因测序、ALT、AST、HBV-DNA定量及乙肝五项的检测。将其中初始用药为LAM治疗的慢性乙肝患者101例分为三组:第一组为发生LAM耐药后换用LAM联合ADV进行治疗者,共71例;第二组为发生LAM耐药后换用恩替卡韦(ETV)联合ADV进行治疗者,共17例;第三组为发生LAM耐药后换用ETV进行治疗者,共13例。另外将初始用药为LAM联合ADV治疗的34例慢性乙肝患者分为两组:第一组为发生耐药后换用ETV进行治疗者,共19例;第二组发生耐药后换用ETV联合ADV进行治疗,共15例。3血液和基因检测各组患者均于换药进行治疗后的3个月、6个月及12个月进行ALT、AST及HBV-DNA定量的检测。其中乙肝病毒耐药基因采用基因测序技术进行检测,ALT、AST采用7600型全自动生化分析仪进行检测,HBV DNA采用荧光定量PCR技术检测,乙肝五项采用ELISA方法进行检测。4数据分析应用SPSS21.0软件进行统计分析。计量资料进行正态性检验,正态分布资料的比较采用t检验;非正态分布资料采用中位数描述,采用秩和检验。HBV DNA取对数计算;以P0.05为差异有统计学意义。结果:1 HBV-P区突变基因位点分型及突变率情况在对石家庄地区454例乙肝患者所感染的乙肝病毒的P区的14个位点的碱基序列进行分析,其中437例检出有为96.3%。所检测的14个位点突变率分别为M204I/V/S 64.3%(292/454)、L180M 38.8%(176/454)、A181V/T/S 22.7%(103/454)、V173L位点9.9%(45/454),N236T位点9.3%(42/454),V207I/L/G位点8.8%(40/454),S213T位点7.0%(32/454),V214A位点5.3%(24/454),M250V/L位点4.4%(20/454),S202G/I位点4.4%(20/454),N/H238T/D位点4.0%(18/454),T184A/G/I/S位点3.5%(16/454),P237H位点2.6%(12/454),Q215S位点1.5%(7/454)。2 LAM耐药的乙肝患者不同挽救方案的HBV DNA载量变化情况LAM耐药的三组乙肝患者换药后第3个月、第6个月、第12个月的HBV DNA载量分别与换药前相比,均呈显著下降,P0.05,差异均具有统计学意义。三组ALT值分别与换药前的ALT值均显著下降,P0.05,差异均具有统计学意义。换用LAM联合ADV方案的AST值分别与换药前相比均呈显著下降,P0.05,差异均具有统计学意义,换用ETV及ETV联合ADV方案的AST值与换药前相比差异不显著,P0.05,无统计学意义。3 LAM联合ADV耐药的乙肝患者不同挽救方案临床疗效结果LAM联合ADV耐药的两组乙肝患者换药后第3个月、第6个月、第12个月的HBV DNA载量分别与换药前相比,均呈显著下降,P0.05,差异均具有统计学意义。换用ETV方案的ALT、AST分别与换药前相比呈下降趋势,但是与换药前相比差异不显著,P0.05,差异无统计学意义;换用ETV联合ADV方案ALT、AST值与换药前相比显著下降,P0.05,差异有统计学意义。结论:1石家庄地区病例HBV P区主要的突变位点中M204I/V/S、L180M和A181V/T/S的突变检出率最高,分别为64.3%、38.8%和22.7%。耐药突变主要对应LAM和ADV耐药。2初始使用LAM治疗的乙肝患者出现耐药后,换用LAM联合ADV方案治疗优于换用ETV和ETV分别联合ADV方案,具有能有效抑制病毒复制,促使肝功能复常,节约成本等优点。3初始使用LAM联合ADV治疗的乙肝患者出现耐药后,换用ETV联合ADV治疗方案进行治疗,综合疗效明显优于ETV单药治疗。
[Abstract]:Objective: to analyze 454 cases of Shijiazhuang area after nucleoside (acid) gene locus mutation type and mutation status of analogues in the treatment of chronic hepatitis B patients in hepatitis B virus resistance, observation of lamivudine (LAM) and LAM combined with adefovir dipivoxil (ADV) gene P of hepatitis B patients in the treatment of patients with mutated dressing, to provide a scientific basis for the method to improve the effect of treatment of chronic hepatitis B liver: 1 Experimental Study of patients with chronic hepatitis B from October 2011 -2016 March in Shijiazhuang fifth hospital patients, diagnostic criteria of the Chinese Medical Association of Hepatology and Chinese Medical Association branch jointly developed the disease prevention and treatment of chronic hepatitis B infection "Guide (2010 Edition) by screening were nucleoside analogue therapy in patients with.2 group of study objects on the object of study were screened for hepatitis B drug resistance gene sequencing ALT, AST, HBV-DNA, and quantitative detection of hepatitis B five. The initial medication for the LAM treatment for chronic hepatitis B patients, 101 cases were divided into three groups: the first group occurred after LAM resistance for treatment with LAM combined with ADV, a total of 71 cases; second groups occurred after LAM resistance change with entecavir (ETV) combined with ADV treatment, a total of 17 cases; third groups occurred after LAM resistance for treatment with ETV, a total of 13 cases. In addition to the initial medication for 34 cases of chronic hepatitis B patients with LAM combined with ADV treatment were divided into two groups: the first group after treatment for drug resistance by ETV. A total of 19 cases; second groups were treated with the change of resistance after ETV combined with ADV, a total of 15 cases of detection of.3 gene and blood patients 3 months after treatment were dressing, ALT 6 and 12 months, the detection of AST and HBV-DNA. The quantitative hepatitis B virus resistance gene by gene sequencing technology detection of ALT AST, with 7600 automatic biochemical analyzer to detect HBV and DNA by fluorescence quantitative PCR detection of hepatitis B five was detected by ELISA method using SPSS21.0.4 data analysis software for statistical analysis. The measurement data was tested for normality, normal distribution data compared with t test; non normal distribution data using the median description using the Wilcoxon rank sum test and.HBV DNA logarithmic calculation based on P0.05; the difference was statistically significant. Results: the nucleotide sequence of 14 loci of 1 HBV-P gene mutation type and mutation rate in the infection of 454 cases of hepatitis B patients with hepatitis B virus P in Shijiazhuang area were analyzed, including 437 cases the detection for 96.3%. detection of 14 mutation rates were 64.3% M204I/V/S (292/454), L180M 38.8% (176/454), A181V/T/S 22.7% (103/454), V173L (45/454), N236T site 9.9% site 9.3% (42/454), V20 7I/L/G site 8.8% (40/454), S213T (32/454), V214A site 7% site 5.3% (24/454), M250V/L (20/454), S202G/I site 4.4% site 4.4% (20/454), N/H238T/D (18/454), T184A/G/I/S site 4% site 3.5% (16/454), P237H (12/454), Q215S site 2.6% site 1.5% (7/454) three groups hepatitis B patients. Hepatitis B patients with.2 resistant LAM HBV DNA different salvage regimens load changes LAM resistance after third months, sixth months, twelfth months HBV DNA load were compared with before dressing, decreased significantly, P0.05, the difference was statistically significant. The three groups respectively with ALT value before dressing ALT values were significantly decreased, P0.05, the difference was statistically significant. Change were decreased significantly, compared with before dressing P0.05 LAM combined with the ADV value of the AST program, the differences were statistically significant, for the ETV and ETV combined with ADV for AST compared with no significant difference before dressing, P0.05, the two groups of patients with hepatitis B was different in patients with hepatitis B was not statistically significant.3 LAM combined with ADV resistant clinical results LAM salvage regimens combined with ADV resistance after third months, sixth months, twelfth months HBV DNA load were compared with before dressing, P0.05 decreased significantly, and the differences were statistically significant for the ETV scheme. ALT, AST respectively and compared before dressing decreased, but the difference was not significant compared with before dressing, P0.05, the difference was not statistically significant; for the ETV combined with ADV for ALT, AST compared with before dressing decreased significantly, P0.05, the difference was statistically significant. Conclusion: 1 cases in Shijiazhuang area HBV P the main mutation sites of M204I/V/S, L180M and A181V/T/S mutation detection rate were 64.3%, 38.8% and 22.7%. mutations mainly correspond to LAM and ADV resistant.2 initial treatment with LAM in patients with hepatitis B is resistant, replaced by LA M combined with ADV regimen in the treatment is better than for the ETV and ETV respectively combined with ADV scheme, which can effectively inhibit virus replication, promote liver function recovery in patients with hepatitis B, saved and cost advantages of.3 initial use of LAM combined with ADV in the treatment of the emergence of drug resistance after treatment with ETV combined with ADV for treatment, the comprehensive curative effect is obviously superior to ETV monotherapy the treatment.

【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R512.62

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