乙型肝炎病毒DNA高敏检测在HBeAg阴性患者治疗监测中的作用

Monitoring by high-sensitivity HBV DNA assay during treatment in chronic hepatitis B e antigen negative patients

目的通过高灵敏乙型肝炎病毒（HBV）载量监测和对HBV基因分型、耐药突变比例的比较，分析替诺福韦酯和阿德福韦酯治疗方案对乙型肝炎病毒e抗原（HBeAg）阴性患者的疗效。方法收集2015年1月至2017年6月门诊和住院的初次确诊为慢性乙型肝炎患者资料，随机均分为替诺福韦酯组和阿德福韦酯组，定量检测两组患者治疗前、治疗12、24、48、96、120周时HBVDNA水平，对HBeAg阴性的患者进行HBVDNA序列测定，确定HBV基因型及耐药突变。比较组间的计量资料采用f检验；组间比较计数资料采用X2检验。结果收集到HBeAg阴性患者资料共106例。相比阿德福韦酯治疗方案（42％），替诺福韦酯对HBVDNA抑制率更高（54％），但差异无统计学意义（P=0．19）。治疗120周后，替诺福韦酯组HBVDNA定量〈2000IU／ml的患者合计46例，占93．9％。阿德福韦酯组HBVDNA〈2000IU／ml的患者合计40例，占75．5％。两组比较，差异有统计学意义（P〈0．05）。对于49例HBeAg阴性患者，替诺福韦酯治疗前，HBVB、C、B和C混合、D基因型患者均检出C1653T、A1762T、G1764A突变位点。B、C、B和C混合型患者检出C1673T、G1896、G1858、G1899A突变位点。治疗后，上述突变位点的检出率均有所下降，未检出C1653T、C1673T、G1899A突变位点，新检出G1915A／C、L180M、M204V、V207I／L、T184A、V173L等突变位点，但是耐药率较低（25％）。结论替诺福韦酯可推荐作为HBeAg阴性患者的治疗方案。对于HBeAg阴性患者，选择高灵敏方法检测HBVDNA水平，可更好地监测抗HBV疗效。

Objective To explore the efficacy oftenofovir disoproxil and adefovir dipivoxil treatment in patients with hepatitis B virus e antigen （HBeAg） negative was analyzed through the comparison of highly sensitive HBV viral load monitoring with HBV genotyping and drug resistance mutations. Methods The clinical data of newly diagnosed chronic hepatitis B patients from January 2015 to June 2017 in outpatients and inpatients were randomly divided into tenofovir and adefovir group. Quantitative detection of HBV DNA levels before therapy and at 12, 24, 48, 96, and 120 weeks after therapy were determined for HBV genotypes and drug- resistant mutations in HBeAg-negative patients. Student＇s t-test was used to compare the measurement data betw een groups. The data of comparison between groups were tested byz2. Results A total of 106 cases of HBeAg-negative patients were collected. Tenofovir disoproxil had a higher rate of HBV DNA suppression （54%） than adefovir dipivoxil treatment （42%）, but the difference was not statistically significant （P = 0.19）. After 120 weeks of treatment, a total of 46 patients （93.9%） were enrolled in the tenofovir disoproxil group with HBV DNA quantitation 〈 2 000 1U / ml. Adefovir dipivoxil group of patients with HBV DNA 〈 2 000 IU / ml a total of 40 cases, accounting for 75.5%. The difference between the two groups was statistically significant （P 〈 0.05）. For 49 cases of HBeAg-negative patients, HBV B, C, B and C were mixed before tenofovir dipivoxil treatment, and C1653T, A1762T and G1764A mutation sites were detected in patients with D genotype. Patients C, B, C, B, and C were examined for C1673T, G1896, G1858, G1899A. After treatment, the detection rate of the above mutation sites decreased, but C1653T, C1673T and G1899A were not detected. New mutation sites such as G1915A / C, L180M, M204V, V207I / L, T184A and V173L were detected, Low resistance rate （25%）. Conclusion Tenofovir disoproxil can be recommended as a treatment for HBeAg-negative patients. For HBeAg-negative patients, the choice of high-sensitivity detection ofHBV DNA levels, better monitoring of anti-HBV efficacy.