拉米夫定联合清肝解毒汤对肝郁脾虚型慢性乙型肝炎多聚酶基因变异的影响

目的观察拉米夫定联合清肝解毒汤治疗肝郁脾虚型慢性乙型肝炎患者对HBVYMDD变异的影响。方法将74例未间断服用拉米夫定治疗1年的未发生YMDD变异的慢性乙型肝炎患者分为对照组34例,治疗组40例,治疗组给予拉米夫定联合清肝解毒汤治疗、对照组给予单独服用拉米夫定治疗,治疗6个月,观察患者YMDD变异、ALT水平的变化。结果治疗3个月后,治疗组YMDD变异发生率为8%,对照组YMDD变异发生率为25%,两组比较,差异无统计学意义（P〉0.05）;治疗6个月后,治疗组治疗YMDD变异发生率为14%,对照组YMDD变异发生率为37%,两组比较,差异有统计学意义（P〈0.05）;治疗组与对照组血清丙氨酸氨基转移酶比较,差异无统计学意义（F=0.238,P〉0.05）;治疗前后血清丙氨酸氨基转移酶比较,差异无统计学意义（F=0.185,P〉0.05）。结论清肝解毒汤联合拉米夫定可减少HBVYMDD变异的发生。     

恩施地区乙型肝炎患者HBV DNA YMDD变异的检测

目的了解恩施地区慢性乙型肝炎（乙肝）患者HBV DNA YMDD变异的情况。方法检测该地区100例乙肝患者ALT水平、HBV DNA载量、HBV YMDD变异,对其HBV DNA YMDD变异情况进行分析。结果 100例乙肝患者中检出HBV DNA YMDD变异共15例（阳性率15%）,已服用拉米夫定者60例,检出YMDD变异12例（阳性率20%）,未服用拉米夫定患者40例,检出YMDD变异3例（阳性率7.5%）。15例YMDD变异患者HBV DNA在5.21×10^4-1.34×10^8copies/ml,ALT水平在38-1100U/L。结论恩施地区乙肝患者YMDD变异可在拉米夫定治疗过程中出现,也可天然存在;尚未发现恩施地区乙肝患者性别、年龄、HBV DNA载量、ALT水平对YMDD变异检出率有显著影响     

阿德福韦酯治疗YMDD变异的慢性乙型肝炎疗效相关因素分析

目的研究分析影响阿德福韦酯治疗YMDD变异的慢性乙型肝炎疗效的相关因素。方法入选并收集阿德福韦酯治疗48周的92例患者临床资料,采用Logistic回归分析影响疗效的相关因素。结果 48周HBV DNA转阴、48周HBeAg转阴或转换和48周ALT复常者较未转阴者的基线HBV DNA水平低;基线ALT≤1ULN、HBV DNA≤5.0 log10 copies/mL者与基线ALT〉1ULN、HBV DNA〉5.0 log10 copies/mL者比较,治疗至48周时的HBV DNA转阴率（χ2=17.321,P〈0.001）、e抗原阳性患者血清学转阴或转换率（χ2=3.88,P=0.049）、ALT复常率（χ2=25.526,P〈0.001）均有统计学意义;Logistic回归分析结果显示,基线HBV DNA低水平、24周HBV DNA转阴、12周YMDD变异转阴是48周获得较好疗效的相关因素。治疗24周时HBV DNA未转阴者继续治疗至48周时仍有24.1%的患者发生HBV DNA转阴。结论对拉米夫定（LAM）治疗出现YMDD变异的慢性乙型肝炎患者采用阿德福韦酯治疗的基线HBV DNA低水平、24周HBV DNA转阴、12周YMDD变异转阴是48周疗效较好的相关影响因素。发生病毒学突破而无生化学突破的患者早期采用阿德福韦酯治疗可获得更佳疗效;治疗24周时HBV DNA未转阴者应继续坚持治疗。     

Effect of chinese medicine therapy for strengthening-Pi and nourishing-shen in preventing lamivudine induced YMDD mutation and its immunologic mechanism

<正>Objective:To observe the effect of Chinese medicine therapy for strengthening-Pi(脾) and nourishing-Shen(肾,SPNS) in preventing lamivudine induced YMDD mutation and its immunological mechanism.Methods:One hundred and sixty chronic hepatitis B(CHB) patients with positive HBeAg were equally assigned to two groups at random:the observation group and the control group.Patients in the observation group were treated with lamivudine combined with SPNS,and those in the control group were treated with lamivudine only,with the treatment lasting for 52 weeks in total.Changes in indexes,including liver function,HbeAg,HBV-DNA,YMDD variation,CD_4,CD_4/CD_8 ratio,interferon-γ(IFN-γ),interleukin-4(IL-4), blood routine,renal function,as well as any adverse reactions that occurred in patients,were observed at different time points.Results:The ALT,AST recovery rate and HBV-DNA negatively inversing rate at the 24th week,the 36th week and the 52nd week were all higher(P0.05);meanwhile,the YMDD mutation rate at the 36th week and the 52nd week was lower(P0.05) in the observation group than in the control group.The posttreatment levels of CD_4,CD_4/CD_8 ratio,IFN-γ,and IL-4 as well as the pre-post treatment difference of these indexes in the observation group were significantly different from those in the control group(P0.05).Conclusion: Chinese medicine SPNS therapy can significantly reduce the YMDD variation of HBV,and the mechanism may be related to its regulation of the CD_4 level,CD_4/CD_8 ratio and Th1/Th2 balance.     

3种方案治疗慢性乙型肝炎YMDD变异的成本-效果分析

目的:评价3种方案治疗慢性乙型肝炎YMDD变异患者的成本-效果。方法:将90例患者随机分为3组,A组采用阿德福韦酯与拉米夫定联合治疗12周后,单用阿德福韦酯治疗36周;B组采用阿德福韦酯与拉米夫定联合治疗48周;C组接受恩替卡韦治疗48周。运用药物经济学方法分析其成本-效果。结果:A、B、C组HBV DNA转阴率成本-效果比分别为12685.6、15481.3、31462.2;以A组为参照,B、C组增量成本-效果比为29501.5、106907.8。A、B、C组丙氨酸氨基转移酶复常率成本-效果比分别为12685.6、14284.9、31462.2;以A组为参照,B、C组增量成本-效果比为19618.5、106907.8。A、B、C组HBeAg/HBeAb转换率成本-效果比分别为76227.9、93120.3、209664.0;以A组为参照,B、C组增量成本-效果比为178350.0、1267621.4。A组治疗48周出现rtA181V和rtN236T变异各1例。结论:B组方案为治疗慢性乙型肝炎YMDD变异患者的较优选择。     

拉米夫定治疗前与治疗期间乙肝病毒YMDD变异研究

目的研究慢性乙型肝炎患者应用拉米夫定治疗前与治疗一年期间的乙肝病毒YMDD变异情况。方法103例接受拉米夫定治疗的慢性乙型肝炎患者,在开始治疗前和治疗第1、4、8个月以及1年时采集患者外周血,提取乙型肝炎病毒DNA,采用单核苷酸多态性分析方法,进行短核苷酸片段测序分析。结果乙型肝炎病毒DNA多聚酶区,使用拉米夫定治疗前,发生YVDD变异者1例,发生YIDD变异者2例;治疗第1月,发生YVDD变异者2例,发生YIDD变异者2例;治疗第4月,发生YVDD变异者3例,发生YIDD变异者4例;治疗第8月,发生YVDD变异者6例,发生YIDD变异者8例;治疗1年时,发生YVDD变异者11例,发生YIDD变异者13例。结论在进行拉米夫定治疗前,乙型肝炎病毒即有变异情况发生,随拉米夫定治疗变异率增加治疗1年时,乙型肝炎病毒发生变异率最高。     

Rapid detection of the hepatitis B virus YMDD mutant using TaqMan-minor groove binder probes

BACKGROUND: TaqMan-minor groove binder (MGB) probes were used in a real-time PCR-based assay for the rapid and accurate detection of hepatitis B virus (HBV) YMDD mutants. METHODS: TaqMan-MGB probes were designed to distinguish between wild-type (YMDD) and mutant (YVDD and YIDD) strains of HBV. The detection limit and sensitivity of the assay were determined using a dilution series of a mixture of wild-type and mutant plasmids. Serum samples collected from four patients with chronic mutant HBV infections during lamivudine therapy were analyzed using this method. RESULTS: The detection limit for YVDD and YIDD was 10 and 50 copies, respectively, whereas the sensitivity was 10% within a mixed virus population. In the clinical samples, mutant strains of HBV could be detected at levels <2.6 log copies/ml of HBV DNA. While 15 of the 21 samples tested by this method were positive for the YMDD mutant, direct sequencing and a reverse hybridization line probe assay (INNO-LiPA HBV DR v2) detected the mutant strain in only 11 and 9 samples, respectively. Moreover, the data for 6 samples analyzed by TA cloning were fully consistent with our TaqMan PCR results. CONCLUSIONS: We successfully established a sensitive and accurate assay for the YMDD mutant of HBV. This method may be useful for monitoring patients treated with lamivudine.     

Alanine aminotransferase is an inadequate surrogate marker for detecting lamivudine resistance

AIM: To investigate the accuracy of serum alanine aminotransferase (ALT) in diagnosing lamivudine resistance and factors that contributed to abnormal serum ALT.METHODS: This was a retrospective study of chronic hepatitis B patients on lamivudine therapy who were followed for 3-mo with liver function tests and hepatitis B virus (HBV) DNA measurement. Lamivudine resistance was defined as HBV DNA ≥ 1 log from nadir on at least 2 occasions, confirmed by genotyping. Serum ALT levels in patients with lamivudine r...     

乙型肝炎病毒YMDD变异对临床病情的影响

目的　研究拉米夫定治疗乙型肝炎出现YMDD变异后对临床病情及病毒量的影响 ,以及YMDD变异与前C区变异的相关性。方法　对 13 5例曾用过拉米夫定治疗后复发的住院病例 ,按检查结果分为两组 ,YMDD变异组 61例 ,未变异组 74例 ,对两组病情诊断、病毒载量、肝功能指标 ,YMDD变异与HBeAg、前C区变异的关系进行对照分析。结果　YMDD变异与未变异在慢性肝炎 (轻度 )分别为 9.8% ( 6/ 61)与 8.1% ( 6/ 74)、慢性肝炎 (中度 )分别为 44 .3 % ( 2 7/ 61)与 48.6% ( 3 6/ 74)、慢性肝炎 (重度 )分别为 2 6.2 % ( 16/ 61)与 2 9.7% ( 2 2 / 74)、慢性重型肝炎分别为 9.8% ( 6/ 61)与 14 .9%( 11/ 74)、肝硬化分别为 4.9% ( 3 / 61)与 10 .8% ( 8/ 74) ,各组比较均无显著性差异 (P >0 .0 5 )。两组病毒载量 <1×10 4copies/ml者分别为 1.6% ( 1/ 16)与 2 0 .3 % ( 15 / 74,P <0 .0 1)、1× 10 4～ 10 6copies/ml者分别为 9.8% ( 6/ 61)与 2 9.7% ( 2 2 /74,P <0 .0 1)、≥ 1× 10 7copies/ml者分别为 88.5 % ( 5 4/ 61)与 5 0 .0 % ( 3 7/ 74,P <0 .0 1)。肝功能 6项指标中ALT、ALB、A/G、TBIL对比无显著性差异 (P >0 .0 5 ) ,AST、PTA对比差异显著 (P <0 .0 5 )。YMDD变异组中HBeAg阳性率 68.9% ( 4 2 / 61) ,未变异