356例乙型肝炎患者病毒分型及拉米夫定治疗所致耐药突变株变化分析

Analysis of 356 patients with hepatitis B virus genotyping and lamivudine treatment due to resistant mutants change

目的分析乙型肝炎患者病毒分型和拉米夫定治疗所致耐药突变株变化。方法运用荧光定量PCR结合DNA分子测序技术对2007年8月—2012年8月本院收治的356例乙型肝炎患者进行HBV分型,并对拉米夫定治疗所致耐药突变株变化进行检测。结果拉米夫定治疗2、6、12及18个月时,外周血中HBV-DNA含量、转阴率、ALT水平均逐渐升高,与治疗前比较差异有统计学意义(P<0.05或P<0.01),HBeAg复常率及转阴率均逐渐升高;门诊检查的乙肝患者与经拉米夫定治疗患者的HBV基因型无显著差异(P>0.05);经拉米夫定治疗的乙肝患者,氨基酸位点173的有12例(3.37%)、位点180的18例(5.06%)、位点204的78例(21.91%)、位点207的7例(1.97%)、位点213的8例(2.25%)。结论经拉米夫定治疗的乙肝患者仍然存在较多的拉米夫定耐药突变菌株;对乙肝患者病毒分型以及拉米夫定治疗所致耐药突变菌株进行及时的监测,能够为临床治疗与用药提供一定的依据。

Objective To investigate the hepatitis B virus genotyping and lamivudine in the treatment of drug-resistant mutants change.Methods Fluorescence quantitative PCR and sequencing of the DNA molecule HBV genotyping and lamivudine were used to detect drug-resistant mutant mutation of 356 patients with hepatitis B admitted to our hospital during August 2007 to August 2012.Results Two months,6 months,12 months and 18 months after lamivudine treatment in peripheral blood of HBV-DNA content,negative rate,and average ALT level gradually increased.The differences were statistically significant（P〈0.05 or P〈0.01）.HBeAg normalization rate and negative rates gradually increased.The HBV genotypes of hepatitis B patients examined in the outpatient Department and patients treated by lamivudine showed no statistical difference（P〈0.05）.Among hepatitis B patients treated with lamivudine,there were 12 with amino acid site 173（3.37%）,18 with site 180（5.06%）,78 with site 204（21.91%）,7 with site 207（1.97%）,and 8 with site 213（2.25%）.Conclusion Lamivudine treatment in patients with hepatitis B persists more lamivudine-resistant mutant strains.Genotyping to patients with hepatitis B virus and timely monitoring of drug-resistant mutant strains caused by lamivudine treatment can provide certain data for clinical treatment and medication.