APPLICATION OF GENE SEQUENCE IN DETERMINING DRUG RESISTANCE MUTANT GENOTYPES IN THE TREATMENT OF CHRONIC VIRAL HEPATITIS B

Hoang Long Do 1,, Thanh Vu Nguyen 2, Cong Hanh Le 1, Do Hung Tran1, Thi Hong Cua Trinh 1, Thi Huong Truc Dinh 1, Chi Dung Le 1
1 Can Tho University of Medicine and Pharmacy
2 Cai Be District Medical Center

Main Article Content

Abstract

Background: Under the selective pressure of hepatitis B antiviral drugs during the treatment of chronic hepatitis B, virus strains with drug-resistant mutations will appear and spread, causing drug resistance and treatment failure. Sequencing is a molecular biology technique that helps determine the genotype of this drug resistance mutation. Objectives: To determine drug-resistant mutant genotypes for chronic hepatitis B virus treatment. Materials and method: Using the convenience sampling method, 71 chronic hepatitis B patients being treated with hepatitis B antiviral drugs such as lamivudine, adefovir, entecavir and tenofovir with positive HBsAg for over 6 months were selected for cross-sectional descriptive study performed at Can Tho University of Medicine and Pharmacy Hospital during the period from July 2022 to June 2023. Blood samples from patients with chronic hepatitis B virus that meet the standards are taken, then real-time PCR technique is carried out first and then sequencing technique later. Results: Two genotypes B and C have been identified in patients with chronic hepatitis B virus receiving antiviral treatment for hepatitis B with rates of 73.2% and 26.8%, respectively. The rate of drug resistance mutations of hepatitis B virus in patients with chronic hepatitis B virus was 7%. There were 2 lamivudine resistance mutations (V207M) and 1 adefovir resistance mutation (Q215H) detected in genotype B. In genotype C, 1 adefovir resistance mutation (Q215H) and 1 entecavir resistance mutation (S202I) were detected. Both genotypes B and C did not detect tenofovir resistance mutations. Conclusion: There are 7% drug resistance mutations of hepatitis B virus in patients with chronic hepatitis B virus. Genotype B has 2 lamivudine resistance mutations (V207M) and 1 adefovir resistance mutation (Q215H), while genotype C has 1 adefovir resistance mutation (Q215H) and 1 entecavir resistance mutation (S202I).

Article Details

References

1. Thu Kim Nguyen, Duyet Van Le. Resistant mutations within the hepatitis B virus reverse transcriptase sequence in treatment failure patients with chronic HBV infection in Vietnam. Journal of Global Antimicrobial Resistances. 2023. 33, 35-41, doi: 10.1016/j.jgar.2023.02.013.
2. European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of Hepatology. 2017. 67(2), 370-398, doi: 10.1016/j.jhep.2017.03.021.
3. Thi Ton That Bui, Tan Thanh Tran, My Ngoc Nghiem, Pierre Rahman, Thi Thanh Thanh Chan, et al. Molecular characterization of hepatitis B virus in Vietnam. BMC Infectious Diseases. 2017. 17(1), 601-609, doi: 10.1186/s12879-017-2697-x.
4. Trịnh Thị Hằng. Xác định đột biến kháng thuốc liên quan đến đột biến ở bệnh nhân viêm gan B mạn tại Bệnh viện Bệnh Nhiệt đới Trung ương từ tháng 1 năm 2014 đến tháng 12 năm 2017. Đại học Y Hà Nội. 2019.
5. Lu L. Antiviral therapy of liver cirrhosis related to hepatitis B virus infection. Journal of Clinical and Translational Hepatology. 2014. 2, 197-201, doi: 10.14218/JCTH.2014.00022.
6. Zhang X., Chen X., Wei M., Zhang C., Xu T., et al. Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection. Scientific Reports. 2019. 9(1), 8078-8086, doi: 10.1038/s41598-019-44604-6.
7. Guo X., Wu J., Wei F., Ouyang Y., Li Q., et al. Trends in hepatitis B virus resistance to nucleoside/nucleotide analogues in North China from 2009-2016: A retrospective study. International Journal of Antimicrobial Agents. 2018. 52(2), 201-209, doi: 10.1016/j.ijantimicag.2018.04.002.
8. Lai M., Lian J., Zhang W., Xu J., Zhou L., et al. Compare with safety and efficacy of entecavir and adefovir dipivoxil combination therapy and tenofovir disoproxil fumarate monotherapy for chronic hepatitis B patient with adefovir-resistant. Mathematical Biosciences and Engineering. 2019. 17(1), 627-635, doi: 10.3934/mbe.2020032.
9. Alacam S., Karabulut N., Yolcu A., Onel M., Atasoy A., et al. Evaluation of drug resistance mutations in patients with chronic hepatitis B. Folia Microbiology (Praha). 2019. 64(2), 237243, doi: 10.1007/s12223-018-0650-z.