Discrepancy of potential antiviral resistance mutation profiles within the HBV reverse transcriptase between nucleos(t)ide analogue‐untreated and ‐treated patients with chronic hepatitis B in a hospital in China

Abstract

Little is known about the discrepancy of the potential antiviral resistance mutation profiles within the hepatitis B virus (HBV) reverse transcriptase (RT) between nucleos(t)ide analogue (NA)-untreated and -treated patients with chronic hepatitis B. Full-length HBV RT sequences from 59 NA-treated and 105 NA-untreated Chinese patients were amplified and sequenced. Forty-two potential NA resistance (NAr) mutation sites were screened within these 164 RT sequences. The NAr mutation prevalence and frequency in the NA-treated group were significantly higher than those in the NA-untreated one (P < 0.001, respectively). The classical primary drug resistance and secondary/compensatory mutations were only detected at seven sites (rtL80, rtI169, rtL180, rtA181, rtT184, rtM204, and rtN236) in NA-treated patients. The non-classical putative NAr and pre-treatment mutations were observed at 22 sites (rtT38, rtN/S53, rtL82, rtL/I91, rtN/Y124, rtH126, rtT128, rtN/D134, rtN139, rtR153, rtV191, rtV207, rtS213, rtV214, rtE218, rtY/F221, rtV/I224, rtL229, rtI233, rtN/H238, rtR242, and rtS/C256) in both groups. Substitutions at seven non-classical mutation sites were of interest due to either detection only in patients with virologic breakthrough (rtL82 and rtV214), or potential ties with HBV genotypes (rtV191 and rtL229), or coexistence with rtM204I/V (rtL229), or increased mutation trends after NA-treatment (rtT128, rtV207, and rtN/H238). In conclusion, NA treatment not only constitutes a major selection factor for the primary and secondary/compensatory NAr mutations but also drives the changes of some of the putative NAr mutation sites, most of which are the genotype-independent RT sites (rtL82, rtT128, rtV191, rtV207, rtV214, rtL229, and rtN/H238). Their antiviral resistance potential calls for further investigations.

Monitoring of genotypic resistance profile in chronic hepatitis B patients receiving nucleos(t)ide analogues in Huzhou, China

“…These finding were supported by previous studies [24,25]. The mutations at rt169 and rt184 residues responsible for ETV resistance were not detected.…”

Antiviral efficacy of adefovir dipivoxil in the treatment of chronic hepatitis B subjects from Indian subcontinent

“…[15] The subject with rtI169L mutation had no history of entecavir treatment. Recently, Li et al, [7] showed rtI169L as primary drug resistance mutation associated with adefovir treatment. This report supports our fi nding and illustrates rtI169L mutation to be associated with adefovir resistance.…”

“…[5] The primary adefovir-resistant mutations are rtN236T and rtA181T/V. [6] Recently, Li et al, [7] showed a novel rtI169L mutation as a primary drug resistance mutation associated with adefovir monotherapy. The cumulative probability of mutations associated with resistance to adefovir is 0%, 3%, 11%, 18% and 29% after 1, 2, 3, 4 and 5 years, respectively.…”

Hepatitis B Virus Carrying Drug-resistance Compensatory Mutations in Chronically Infected Treatment-naive Patients

“…In recent studies conducted with non-treated patients in different countries, it was shown that the frequencies of HBV strains which had clinically important drug resistance mutation (NA resistance) were between 0.5% and 1% (17,18,19,20,21,22,23,24,25 (29) evaluated 30 CHB patients who were not previously treated and they determined HBV NA resistance-related mutations in 3 of them (10%).…”