Abstract: Objective To investigate and analyze the natural drug resistance mutations of 268 patients with chronic hepatitis B viral (HBV) infection in Nanjing, and analyze the relevant factors affecting the occurrence of natural resistance mutations to nucleos(t)ide analogues of anti-HBV drugs. Methods The data of 268 patients with chronic HBV infection in Nanjing from October 2019 to October 2022 were analyzed retrospectively. The occurrences of natural drug resistance and the types of drug resistance mutations were counted. The clinical characteristics of patients with and without mutations were compared. Logistic analysis was used to analyze the relevant factors affecting the occurrence of natural drug resistance mutations in these patients. Results In 268 patients with chronic HBV infection, a total of 9 natural drug-resistant mutations were detected by gene sequencing, the detection rate was 3.36% (9/268). The drug resistance sites of the 9 patients with natural drug resistance mutations were rt180M, rt204V, rt204I, rt250V, rt180M, rt204V+rt180M, rt213T, rt236T and rt204I+rt180M, respectively. The age, HBV DNA load, and the course of disease in patients with mutation were higher than those without mutation (P<0.05). By logistic multivariate regression analysis it was shown that age, HBV DNA level and the course of disease were independent risk factors for the occurrence of natural drug-resistant mutations in patients with chronic HBV infection (OR=4.162, 4.411, 5.766, P<0.05). Conclusion There are natural drug-resistant mutations in chronic HBV infected people in Nanjing area. Age, HBV DNA level, the course of disease are independent risk factors that affect the occurrence of natural drug-resistant mutations in chronic HBV infected patients, Prevention should therefore be strengthened.

Key words: Hepatitis B virus, Genotype, Gene resistance, Natural drug resistance mutation