Analysis of risk factors for drug resistant mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients

Abstract

Objective: To analyze the risk factors that may affect the mutations in the reverse transcriptase region in chronic hepatitis B virus-infected patients. Methods: 678 hospitalized cases with chronic HBV infection who underwent HBV RT testing at Tianjin Second People's Hospital from January 1, 2016 to December 31, 2016 were collected retrospectively. Among them, 417 cases were diagnosed with chronic hepatitis B, 219 cases with liver cirrhosis and 42 cases with primary liver cancer. There were 268 cases of non-use of any antiviral therapy, 138 cases of discontinuation of antiviral drugs for 6 months or more, and 272 cases of continuous antiviral therapy. HBV genotyping and RT region mutation sites were detected by direct sequencing. The risk factors that may affect the drug resistant mutation in the HBV RT mutation, including age, genotype, antiviral drug selection and medication time, hepatitis B virus infection, and biochemical markers were analyzed by univariate analysis to screen out independent risk factors. Results: Among 678 HBV-infected cases, 290 cases (42.8%) were detected with RT-region mutation. Among them, the pre-existing drug resistant rate was 6.72%, and the drug resistant mutation rate was 23.19% in treated patients. The drug resistant mutation rate of patients with continuous antiviral therapy was 66.18%. Gene mutations highest rate for 1 ~ 5 years was 27.14% in chronic HBV patients treated with antiviral therapy. Logistic regression analysis of the factors that had led to HBV mutation showed that old age, the selection of nucleoside drugs at the beginning of treatment and medication time were the main factors affecting HBV RT mutations. Conclusion: Abnormal ALT level, HBV genotype, HBV DNA quantitative level are the main factors influencing non-drug resistant mutations. Age over 60 years old, and long-term use of low-barrier nucleoside drugs are high-risk groups for HBV resistant. Therefore, HBV resistant monitoring should be strengthened.