Abstract: Objective To explore the status of drug resistance in patients with chronic hepatitis B （CHB） and gene mutation sites of common nucleoside （acid） drug resistance. Methods From January 1, 2020, to September 30, 2021, patients with CHB in Kaifeng Infectious Diseases Hospital and Huaihe Hospital, Henan University were selected as the research objects. The case data were collected retrospectively and gene mutation sites of common nucleoside （acid） drug resistance were detected. The results were analyzed by the descriptive analysis method. Results A total of 2 141 CHB patients were included in this study, including 1 635 males and 506 females, aged 20-42 years, with an average of （31.5±10.5） years old, and HBV DNA load of （4.88±1.54）×10⁷ U/mL. The drug resistance rate of CHB patients aged 30-42 years was significantly higher than that of patients aged 20-29 years （P<0.01）. CHB patients were highly resistant to lamivudine and were more sensitive to tenofovir disoprox and adefovir dipivoxil. Among 2 141 CHB patients, 788 cases of HBV drug resistance gene mutation were detected, accounting for 36.81%. M204I, M204V, and M250I+M250L were the top three HBV drug resistance mutation sites, accounting for 22.08%, 13.20%, and 9.64%, respectively. B genotype patients were mainly （62.20%）. The gene mutation rate of C genotype and B+C mixed genotype patients was significantly higher than that of B genotype patients, and the multi-gene mutation rate of B genotype patients was significantly higher than that of C genotype and B+C mixed genotype patients （P<0.01）. There was no significant difference in the mutation rate of drug resistance genes between the single-drug therapy group and the multiple-drug sequential therapy group （P>0.05）. The mutation rate of the drug resistance gene in the drug withdrawal group was higher than that in the non-drug withdrawal group （P<0.01）. Conclusion Long-term common nucleoside （acid） drugs often appear clinical resistance, which can lead to various forms of HBV polymerase denaturation, which is the main obstacle to the treatment of HBV infection. Clinical detection of drug-resistant mutation sites is conducive to the formulation of treatment plans and guides the selection of therapeutic drugs and long-term prevention and treatment.

Key words: Chronic hepatitis B, Drug resistance, Nucleoside （acid） drugs, Gene mutation sites of drug resistance