Trends in Hepatitis B Virus Resistance to Nucleoside/nucleotide Analogues in North China from 2009-2016: A Retrospective Study

Nucleos(t)ide analogues (NAs) are widely used in anti-hepatitis B virus (anti-HBV) therapy for effective inhibition of HBV replication. However, HBV resistance to NAs has emerged, resulting in virus reactivation and disease recurrence. Data on the current dynamics of HBV resistance are still rare in China. This study analysed 4491 plasma samples with HBV primary genotypic resistance mutations representative of the general HBV resistance situation in northern China from 2009-2016. We found that entecavir (ETV), representing 57.6% (12 713/22 060) of NA users in North China in 2016, has become the major NA for treating Chinese patients infected with HBV. Despite >50% of M204I/V±L180M among all HBV resistance cases annually and extensive exposure of patients to lamivudine (LAM), telbivudine (LdT) and adefovir dipivoxil (ADV), ETV resistance also showed a dramatically increased incidence, which rose to 17.1% in 2016. Moreover, A181T/V, ETV resistance mutations and multidrug resistance mutations were found more frequently in HBV genotype C compared with genotype B (21.2% vs. 8.5%, 12.4% vs. 7.9% and 5.9% vs. 3.0%, respectively), whereas M204I and N236T were more predominant in genotype B than genotype C (40.3% vs. 20.8% and 11.3% vs. 1.8%, respectively). In conclusion, we report the dynamic changes of HBV NA resistance mutation patterns and the current NA usage profile for anti-HBV treatment in North China over the past 8 years. These data provide valuable information on HBV NA resistance that is an important reference for clinicians to devise more effective treatment regimens for individual patients.