[Analysis of characteristics of drug resistance gene mutation in HBV RT region of hepatitis B infected patients].

Objective: This article investigated the clinical characteristics and distribution of drug resistance mutation sites in HBV RT region of hepatitis B infected patients. Methods: Retrospective analysis was made on 1 948 patients with HBV infection, who had been tested for NAs resistance mutation and had a medical history of NAs in the Laboratory Department of the Fifth Medical Center of the PLA General Hospital from January 2020 to December 2021. Basic clinical information and drug resistance related mutation information were recorded. Meanwhile, the serological index data of hepatitis B were collected. Drug resistance gene mutant group and non-mutated group were grouped according to whether the drug resistance genes had a mutation in HBV RT region, and the clinical characteristics and genotype distribution of the two groups were statistically analyzed. The pattern of drug resistance gene mutation, number of mutation sites, drug resistance type and mutation of NAs resistance-related sites were analyzed in 917 patients with drug resistance gene mutation in HBV RT region. χ2 Inspection was used for counting data. Meanwhile, two independent samples t-test and Wilcoxon rank sum test were used for measurement data. Results: Among the 1 948 patients with chronic HBV infection, 917 patients had drug resistance gene mutation in RT region (47.07%). The proportion of patients with acute hepatitis B and CHB in HBV RT resistance gene mutant group was lower than that in the non-mutated group, while the proportion of patients with HBV-related cirrhosis was higher than that in the non-mutated group, these differences were statistically significant. Compared with the non-mutated group in HBV RT region, the age, the positive rates of HBeAg and HBV DNA, and HBV DNA load of these patients were increased in drug resistance gene mutant group, these differences were statistically significant. Genotypes of patients in both groups were dominated by C, followed by B and D. The proportion of patients with genotype C in HBV RT drug resistance gene mutant group was higher than that of non-mutated group, the difference was statistically significant. There were 53 gene mutation patterns in 917 patients with drug resistance gene mutation in HBV RT region, and the main pattern was rtL180M+rtM204V+rtS202G (9.70%). The mutation sites were dominated by 3 (20.74%). There were 5 types of drug resistance, LAM+Ldt (21.25%) was the most. Among the 18 sites that were clearly associated with LAM, ADV, ETV and Ldt resistance in the HBV RT region, 14 sites were mutated, and the most common mutation sites were rtL180M, rtM204V, rtM204 and rtS202G. what's more, the proportion of patients with NAs drug resistance was LAM>Ldt>ETV>ADV. Conclusion: In order to prevent adverse consequences of this study such as disease recurrence or disease progression caused by HBV drug resistance, HBV infected patients, who have long-term use of NAs antiviral therapy, should monitor the level of HBV DNA and drug resistance genes in HBV RT region in order to optimize the treatment plan in time or guide individualized treatment.目的： 探讨乙肝感染患者HBV RT区耐药基因突变的临床特征及耐药位点的分布情况。 方法： 回顾性分析2020年1月至2021年12月在解放军总医院第五医学中心检验科进行NAs耐药基因突变检测且既往有明确应用NAs史的1 948例HBV感染患者，记录其基本临床信息及耐药相关突变信息，同时收集其乙肝血清学指标数据。根据HBV RT区耐药基因是否变异分为耐药基因变异组和未变异组，并对两组结果的临床特征和基因型分布进行统计分析。同时，将917例HBV RT区耐药基因变异患者的耐药基因变异模式、突变位点数、耐药类型以及NAs耐药相关各位点突变情况进行统计分析。计数资料采用χ2检验，计量资料采用两独立样本t检验和Wilcoxon秩和检验。 结果： 1 948例HBV感染患者中有917例（47.07%）发生RT区耐药基因变异。HBV RT区耐药基因变异组急性乙型肝炎和慢性乙型肝炎患者比例均低于未变异组，而HBV相关性肝硬化患者比例高于未变异组，差异具有统计学意义。同时，HBV RT区耐药基因变异组患者的年龄、HBeAg阳性率、HBV DNA阳性率以及载量均高于未变异组，差异具有统计学意义。两组患者的基因型均以C基因型（82.39%）为主，B基因型（16.17%）次之，D基因型（1.44%）最少；HBV RT区耐药基因变异组C基因型患者比例高于未变异组，差异具有统计学意义。917例HBV RT区耐药基因变异患者的基因变异模式有53种，最主要模式为rtL180M+rtM204V+rtS202G（9.70%）；其突变位点数以3位（20.74%）为主；耐药类型共有5类，以LAM+Ldt（21.25%）最多。与LAM、ADV、ETV和Ldt耐药明确相关的HBV RT区18个位点中有14个位点检出突变，最常见的突变位点是rtL180M、rtM204V、rtM204I和rtS202G；发生NAs耐药相关的患者比例LAM>Ldt>ETV>ADV。 结论： 为预防HBV耐药导致疾病反复或疾病进展等不良后果，长期使用NAs抗病毒治疗的HBV感染患者应监测HBV DNA水平和HBV RT区耐药基因，以期及时优化治疗方案或指导个体化治疗。.