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

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

doi:10.2147/IDR.S249476

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

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

Authors

Fuchu Qian^{1

2}, Weihua Zou³, Fang Jin^{1

2}, Dongli Li^{1

2}, Yujuan Shen⁴

Affiliations

¹ Department of Precision Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
² Huzhou Key Laboratory of Molecular Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
³ Department of Laboratory Medicine, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.
⁴ Department of Infectious Diseases, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, People's Republic of China.

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 (<10⁶ IU/mL) was an independent factor associated with potential DR-related variants in untreated CHB patients (P <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.

Keywords: Hepatitis B virus; potential; resistance; reverse transcriptase; variants.

Grants and funding

This work was supported by the grant from the National Key Programs for Infectious Diseases of China (2017ZX10103008-005) and the Foundation Projects for Science and Technology of Huzhou City (NO. 2017GY30, NO.2019GY02).