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未接受核苷(酸)类似物治疗的中国慢性乙型肝炎患者中潜在耐药相关变异的流行情况

Prevalence of Potential Resistance Related Variants Among Chinese Chronic Hepatitis B Patients Not Receiving Nucleos(T)ide Analogues.

作者信息

Qian Fuchu, Zou Weihua, Jin Fang, Li Dongli, Shen Yujuan

机构信息

Department of Precision Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.

Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.

出版信息

Infect Drug Resist. 2020 Jul 17;13:2407-2416. doi: 10.2147/IDR.S249476. eCollection 2020.

Abstract

BACKGROUND AND AIMS

Potential drug resistance (DR) related variants in the hepatitis B virus (HBV) reverse transcriptase (RT) region may be associated with the effectiveness of antiviral drugs and disease progression. The aim of this study was to investigate the prevalence and clinical characteristics of potential DR-related variants in Chinese CHB patients not receiving nucleos(t)ide analogues (NAs).

PATIENTS AND METHODS

Two hundred and six untreated CHB patients from Huzhou Central Hospital in eastern China were recruited for this study. The serum DNA was extracted and the HBV RT region was amplified using nest polymerase chain reaction (nest-PCR). The 42 potential DR-related variants were analyzed by direct sequencing.

RESULTS

Among these CHB patients, HBV genotype B and genotype C were identified in 121 (58.7%) and 85 (41.3%) patients, respectively. Potential DR-related variants were detected in 42.7% (88/206) of patients. Primary and secondary DR variants were found in 7.3% (15/206) of patients, including rtL80I/V, rtI169T, rtV173L rtL180M, rtA181T/V, rtM204I/V, and rtN236T. The variants at rt53, rt82, rt221, rt233, rt237, and rt256 were specific for genotype B, and those at rt38, rt84, rt126, rt139, rt153, rt191, rt214, rt238, and rt242 were specific for genotype C. Moreover, the variation frequency in the A-B interdomain (3.96%) was significantly higher than that in the functional domains (1.17%) and non-A-B interdomains (1.11%). Multivariate logistic regression analysis showed that lower HBV-DNA load (<10 IU/mL) was an independent factor associated with potential DR-related variants in untreated CHB patients ( <0.05).

CONCLUSION

Potential DR-related variants were frequent and complex in untreated Chinese CHB patients. Furthermore, the variants may contribute to decreased serum HBV-DNA loads. However, the effects of potential DR-related variants on the antiviral therapy and liver disease progression require further study.

摘要

背景与目的

乙型肝炎病毒(HBV)逆转录酶(RT)区域中潜在的耐药相关变异可能与抗病毒药物的疗效及疾病进展相关。本研究旨在调查未接受核苷(酸)类似物(NA)治疗的中国慢性乙型肝炎(CHB)患者中潜在耐药相关变异的流行情况及临床特征。

患者与方法

招募了来自中国东部湖州市中心医院的206例未经治疗的CHB患者进行本研究。提取血清DNA,采用巢式聚合酶链反应(巢式PCR)扩增HBV RT区域。通过直接测序分析42个潜在的耐药相关变异。

结果

在这些CHB患者中,分别在121例(58.7%)和85例(41.3%)患者中鉴定出HBV B基因型和C基因型。42.7%(88/206)的患者检测到潜在的耐药相关变异。7.3%(15/206)的患者发现了主要和次要耐药变异,包括rtL80I/V、rtI169T、rtV173L、rtL180M、rtA181T/V、rtM204I/V和rtN236T。rt53、rt82、rt221、rt233、rt237和rt256位点的变异为B基因型所特有,而rt38、rt84、rt126、rt139、rt153、rt191、rt214、rt238和rt242位点的变异为C基因型所特有。此外,A - B结构域间的变异频率(3.96%)显著高于功能结构域(1.17%)和非A - B结构域间(1.11%)。多因素逻辑回归分析显示,较低的HBV - DNA载量(<10 IU/mL)是未治疗CHB患者中与潜在耐药相关变异相关的独立因素(<0.05)。

结论

未治疗的中国CHB患者中潜在的耐药相关变异频繁且复杂。此外,这些变异可能导致血清HBV - DNA载量降低。然而,潜在耐药相关变异对抗病毒治疗及肝病进展的影响仍需进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c3e/7381783/4b63b99d63d3/IDR-13-2407-g0001.jpg

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