Analysis of Drug Resistance Mutation-related Sites in 1 452 Chronic Hepatitis B Patients with Low Viral Load in Kunming Area
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摘要:
目的 对昆明地区低病毒载量乙肝患者进行基因分型及耐药突变位点的分析研究，为低载量乙肝患者临床抗病毒治疗难易程度的判定及抗病毒精准医疗个体化方案的制定提供依据。 方法 选取1452例低病毒载量（HBV DNA《2.0x103 IU/mL）慢性乙型肝炎患者，进行乙肝分型和耐药基因位点检测。 结果 昆明地区乙肝低载量人群中HBeAg阴性者占比较高（59.5%），男性患者占比（70.6%）高于女性，年龄分布以30～60岁为主（72.7%），基因分型以C基因型占比最高（61.8%）。1 452例昆明地区低载量乙肝患者中共有37例患者检出耐药突变位点，其中拉米夫定与恩曲他滨耐药率一致（1.6%），替比夫定耐药率为1.2%，阿德福韦耐药率0.9%，恩替卡韦耐药率0.2%，替诺福韦未检出耐药突变位点。除耐药突变位点外，还检出其他突变位点112例，其中S256G、S213T、N/H238T/D、Q215H检出率最高，检出率最低的突变位点为A194T。 结论 昆明地区乙肝基因型以C型为主，提示该地区的 HBV 基因型分布状况有独立特征。昆明地区低病毒载量乙肝患者恩替卡韦的耐药率最低，未发现 TDF耐药，但存在替诺福韦酯药物敏感性下降。检出的其他突变位点是否与耐药性相关，仍存在一定的争议，但其检出率也存在一定的占比。 Abstract:Objective To analyze and study the genotyping and drug resistance mutation sites of hepatitis B patients with low viral load in Kunming, so as to determine the difficulty of clinical antiviral treatment for low viral load hepatitis B patients and formulate individualized antiviral precision medicine programs. Methods A total of 1452 chronic hepatitis B patients with low viral load （HBV DNA < 2.0×10 3 IU/mL） were selected for hepatitis B typing and drug resistance gene loci detection. Results The proportion of HBeAg-negative patients in the low-load hepatitis B population in Kunming was higher （59.5%）, and the proportion of male patients （70.6%） was higher than that of female patients. The age distribution was mainly 30-60 years old （72.7%）. Genotyping The C genotype accounted for the highest proportion （61.8%）. Among the 1 452 low-load hepatitis B patients in Kunming area, a total of 37 patients were detected with drug-resistant mutation sites. The drug resistance rates of lamivudine and emtricitabine were consistent （1.6%）, and the drug resistance rate of telbivudine was the same 1.2%, adefovir resistance rate was 0.9%, entecavir resistance rate was 0.2%, and tenofovir resistance mutation sites were not detected. In addition to drug resistance mutation sites, 112 other mutation sites were also detected, among which S256G, S213T, N/H238T/D, Q215H had the highest detection rate, and the mutation site with the lowest detection rate was A194T. Conclusion The hepatitis B genotype in Kunming is mainly C type, which indicates that the distribution of HBV genotype in this area has independent characteristics. The resistance rate of entecavir in patients with hepatitis B with low viral load in Kunming area was the lowest, and TDF resistance was not found, but their sensitivity to tenofovir dipivoxil decreased. There is still some controversy whether the detected other mutation sites are related to drug resistance, but the detection rate also has a certain proportion. -
Key words:
- HBV /
- Low viral load /
- Genotype /
- Drug resistance /
- Mutation sites
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表 1 昆明地区乙肝低载量人群分布特征
Table 1. Population distribution characteristics of the chronic hepatitis B patients withlowviral.l.oadin Kunming
人群特征 例数（n） 构成比（%） HBeAg − 864 59.5 + 588 40.5 性别 男 1 025 70.6 女 427 29.4 年龄 < 30 135 9.3 30-60 1 055 72.7 > 60 262 18.0 型别 B 553 38.1 C 897 61.8 D 2 0.1 
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表 2 昆明地区低载量乙肝患者耐药分布情况
Table 2. Drug resistance distribution of the chronic hepatitis B patients withlowviral.l.oadin Kunming
药物名称 例数（n） 耐药率（%） 拉米夫定（LAM） 23 1.6 恩曲他滨（FTC） 23 1.6 替比夫定（LDT） 18 1.2 恩替卡韦（ETV） 5 0.2 阿德福韦（ADV） 15 1.0 替诺福韦（TDF） 0 0
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表 3 昆明地区低载量人群耐药位点分布情况
Table 3. Drug resistance sitesdistribution of the chronic hepatitis B patients withlowviral.l.oadin Kunming
位点名称 耐药种类 例数（n） 占比（%） A181T/V ADV 8 21.6 N236T 2 5.4 A181T/V+N236T 4 10.8 M204V LAM FTC 5 13.5 M204I LAM FTC LDT 5 13.5 M204V+L180M 6 16.2 M204I+T184L 1 2.7 A181T+ M204I ADV LAM FTC LDT 1 2.7 M204V +L180M+S202G LAM FTC EFV LDT 2 5.4 M204V +L180M+V173L 2 5.4 M204V +L180M+V173L+M250V 1 2.7
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表 4 其他突变位点检出情况
Table 4. Detection of other mutation sites
位点名称 例数（n） 占比（%） N/H238T/D 18 16.1 Q215H 16 14.3 I233V 8 7.1 V214A 4 3.6 V191I 4 3.6 V207M 10 8.9 L229V 10 8.9 S213T 18 16.1 A200V 3 2.7 S256G 19 16.9 A194T 2 1.8
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