Int J Antimicrob Agents. 2018 Apr 11. pii: S0924-8579(18)30104-3. doi: 10.1016/j.ijantimicag.2018.04.002. [Epub ahead of print]
Trends in Hepatitis B Virus Resistance to Nucleoside/Nucleotide Analogs in North China from 2009 to 2016: A Retrospective Study.Guo X1, Wu J2, Wei F1, Ouyang Y1, Li Q2, Liu K1, Wang Y1, Zhang Y3, Chen D4. Author information 1Beijing You An Hospital, Capital Medical University, Beijing, 100069, China.; Beijing Institute of Hepatology, Beijing, 100069, China.; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing, 100069, China.2Beijing You An Hospital, Capital Medical University, Beijing, 100069, China.3Beijing You An Hospital, Capital Medical University, Beijing, 100069, China.. Electronic address: [email protected].4Beijing You An Hospital, Capital Medical University, Beijing, 100069, China.; Beijing Institute of Hepatology, Beijing, 100069, China.; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing, 100069, China.; Organ Transplantation Center, the Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province, 266003, China.. Electronic address: [email protected].
AbstractNucleos(t)ide analogs (NAs) are widely used in anti-hepatitis B virus (HBV) therapy for effective inhibition of HBV replication. However, HBV resistance to NAs has emerged, resulting in virus reactivation and disease recurrence. Big data on the current dynamic of HBV resistance profiles are still rare in China. Herein, we analyzed 4,491 plasma samples with HBV primary genotypic resistance mutations representative of the general HBV resistance situation in northern China from 2009 to 2016. We found that entecavir (ETV), representing 52.8% of 12,713 NAs users in the North of China in 2016, has become the major NA for treating Chinese patients infected with HBV. Despite more than 50% of M204I/V±L180M among all HBV resistance cases annually and extensive exposure of the patients to lamivudine (LAM), telbivudine (LdT), and adefovir dipivoxil (ADV), ETV resistance also showed dramatically increased incidence, which climbed to 17.1% in 2016. Moreover, A181T/V, ETV-resistant mutations, and multidrug-resistant mutations were found more frequently in HBV genotype C than in HBV genotype B, 21.2% vs. 8.5%, 12.5% vs. 7.9%, and 5.9% vs. 3%, respectively, whereas M204I and N236T were more predominant in genotype B than in genotype C, 40.3% vs. 20.8%, and 11.3% vs. 1.8%, respectively. In conclusion, we have reported dynamic changes of HBV NA-resistance mutation patterns and the current NA usage profile for anti-HBV treatment in North China in the past 8 years. Our data provides valuable information on HBV NA resistance that is an important reference for clinics to devise more effective treatment regimens for individual patients.
KEYWORDS: Drug resistance; HBV mutation; Hepatitis B virus; Nucleos(t)ide analogs