Incidence of natural resistance mutations in naïve chronic hepatitis B patients: A systematic review and meta‐analysis

Abstract

The resistance mutations occurred frequently in untreated CHB patients, especially in China. The lamivudine resistance had the highest natural prevalence rate, while other nucleos(t)ide analogues showed rarely spontaneous resistance. Detecting the spontaneous resistance mutations will benefit the clinical management of CHB patients.

Genotyping of HBV and tracking of resistance mutations in treatment-naïve patients with chronic hepatitis B

“…They found genotype C HBV infection, male, and HBeAg negative patients had a slightly higher natural mutation rate when compared with genotype B and D HBV infection, female, and HBeAg positve patients. The ALT serum levels showed no influence on the emergence of antiviral resistance mutations 44. In Brazil, there are few studies that were conducted on survey resistance mutations to NA on naïve patients seeking clinical association 45–47.…”

“…However, Zhang et al44 conducted a meta-analysis to apprise the incidence of natural resistance mutations in naïve chronic hepatitis B patients. They found genotype C HBV infection, male, and HBeAg negative patients had a slightly higher natural mutation rate when compared with genotype B and D HBV infection, female, and HBeAg positve patients.…”

Prevalence of hepatitis B antiviral drug resistance variants in North American patients with chronic hepatitis B not receiving antiviral treatment

“…A systematic review and meta‐analysis of the prevalence of HBV‐DR variants from 106 studies involving 12 212 patients with chronic HBV infection who had not received prior NUC therapy found that the global prevalence of all mutations (primary and secondary) was 5.7%, 5.4% for primary and 2.9% for secondary HBV‐DR variants . There was significant geographical variation with the highest prevalence in China where the pooled prevalence rate of primary and secondary DR variants based on >8000 patients was 8% (95% CI 6.63‐9.38) while the pooled prevalence rate in other countries was 1.9% (95% CI 1.06‐2.69).…”

“…This is of most concern in countries where NUCs with low barrier to resistance are frequently used as first‐line therapy. A meta‐analysis of 106 studies examining the prevalence of HBV‐DR variants in 12 212 persons with chronic HBV infection who had never received NUCs found an overall prevalence of 5.73% (95% confidence interval [CI]: 4.85%‐6.61%); however, there were wide geographical variations ranging from 20% in Africa to 0% in Brazil . An important reason for the wide range in results is differences in sensitivities of assays used to detect DR variants.…”

“…A meta-analysis of 106 studies examining the prevalence of HBV-DR variants in 12 212 persons with chronic HBV infection who had never received NUCs found an overall prevalence of 5.73% (95% confidence interval [CI]: 4.85%-6.61%); however, there were wide geographical variations ranging from 20% in Africa to 0% in Brazil. 6 An important reason for the wide range in results is differences in sensitivities of assays used to detect DR variants. Sensitivities of assays used in these studies range from Sanger or population sequencing which can only detect variants present in ≥20% of the virus pool, line probe (reverse hybridization assay) or mass spectrometry which can detect variants present in roughly 5% of the virus pool, to next generation sequencing (NGS) which can detect variants present in <1% of the virus pool.…”