Evaluation of Hepatitis B Virus Nucleos(t)ide Analogues Resistance mutations in Treatment-Naïve Patients: A Systematic Review and Meta-Analysis

Abstract Background: For detection of the nucleus(t)ide analog resistance (NAr) mutants among Hepatitis B virus (HBV) quasispecies, the selection of appropriate methodologies is necessary. Here, we aimed to investigate the role of different methods for the detection of NAr mutations among treatment-naïve patients with chronic HBV (CHB) infection.Methods: In this systematic review and meta-analysis study, five databases were searched. Desired data were extracted from the selected studies. The I2 was used as an indicator of heterogeneity. The NAr mutations rate was investigated with a 95% confidence interval (CI).Results: The overall ratio of occurrence of NAr within treatment-naïve CHB patients (14653) from 128 studies was 0.085 (95% CI, 0.069-0.103, p-value < 0.0001). Direct sequencing was the most prevalent method of DNA sequencing (56.25%). The rates of NAr mutations in the different methodologies, including the direct sequencing, InnoLipa, NGS, and PASS, were 0.079 (0.037-0.160, p < 0.0001), 0.058 (0.021-0.152, p < 0.0001), 0.729 (0.441-0.902, p = 0.114), and 0.448 (0.281-0.628, p = 0.001), respectively.Conclusions: Drug-resistant quasispecies of HBV exist in treatment-naïve patients in relatively high abundance. More sensitive methodologies like NGS should be used for detecting NAr fractions of the viral population. Replacement of current therapy with novel anti-HBV candidates also should be considered.