Genotyping and drug resistance mutation analysis of hepatitis B virus in chronic hepatitis B patients in West China Hospital_West China Medical Journal

Authors：

TAO Xintong , ZHOU Yi , ZHAO Zhenzhen , WANG Nian , ZHOU Juan ,  SONG Xingbo

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;

Corresponding author：

SONG Xingbo, Email: songxingbo1981@163.com

Keywords：

Chronic hepatitis B; Hepatitis B virus; Genotype; Drug resistance mutations

DOI：

10.7507/1002-0179.201907065

Video：

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Objective To analyze hepatitis B virus (HBV) genotype distribution and drug-resistant mutations in West China Hospital of Sichuan University, providing basis for hepatitis B individualized treatment.Methods A total of 786 chronic hepatitis B patients admitted to West China Hospital of Sichuan University from January 2016 to December 2018 were enrolled in the study. Genotype and drug-resistant mutations were analyzed by Sanger sequencing, and statistical analysis was conducted by χ² test.Results Three genotypes (B, C and D) were identified in 786 samples, 489 (62.2%) in genotype B, 291 (37.0%) in genotype C , and 6 (0.8%) in genotype D. The distribution differences of B and C genotypes in age and ethnic groups were statistically significant (P<0.05). Among them, 627 cases had drug-resistant mutations, with a drug-resistant mutation rate of 79.8%. A total of 262 cases (33.3%) were resistant to lamivudine and tibivudine, 102 cases (13.0%) were resistant to lamivudine, tibivudine and entecavir; 83 cases (10.6%) were resistant to adefovir dipivoxil. No tenofovir resistant strains were detected in 786 samples. There were statistically significant differences in drug resistance between B and C genotypes (χ²=14.356, P<0.01). The most common single mutation was M204I [179 cases (22.8%)], followed by 46 cases (5.9%) of A181V/T associated with adefovir dipivoxil resistance. The most common mixed mutation was L180M+M204V/I in 83 cases (10.6%), and another 102 cases (13.0%) showed M250V and/or V173L and/or T184A/G/S/I and/or S202G/I with L180M+M204V/I.Conclusions HBV genotypes in West China Hospital of Sichuan University are mainly B and C, and the situation of drug resistance is severe and the mutation pattern is complex. Therefore, detecting HBV genotype and drug resistance mutation is necessary, which may develop better clinical treatments.

Citation： TAO Xintong, ZHOU Yi, ZHAO Zhenzhen, WANG Nian, ZHOU Juan, SONG Xingbo. Genotyping and drug resistance mutation analysis of hepatitis B virus in chronic hepatitis B patients in West China Hospital. West China Medical Journal, 2019, 34(8): 890-894. doi: 10.7507/1002-0179.201907065 Copy

1.	GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2015, 385(9963): 117-171.
2.	崔富强, 庄辉. 我国乙型肝炎防控工作进展、挑战及对策. 中国病毒病杂志, 2016(2): 81-87.
3.	Liu CJ, Kao JH. Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J. Semin Liver Dis, 2013, 33(2): 97-102.
4.	Croagh CM, Desmond PV, Bell SJ. Genotypes and viral variantsin chronic hepatitis B: a review of epidemiology and clinical relevance. World J Hepatol, 2015, 7(3): 289-303.
5.	申静, 刘薇拉, 王菲. 太原地区乙肝病毒基因分型与临床指标的相关性分析. 中国卫生检验杂志, 2015, 25(14): 2383-2385.
6.	中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南 (2015 年版). 中华实验和临床感染病杂志 (电子版), 2015, 9(5): 570-589.
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12.	Liu F, Chen L, Yu DM, et al. Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy. Gut, 2011, 60(9): 1269-1277.
13.	张爱民, 王慧芬, 王海滨, 等. 中国 30 个地区 HBV 基因型分布特点和临床意义. 中华实验和临床病毒学杂志, 2011, 25(2): 126-128.
14.	张嘉刚, 杨秀兰, 于国英. 青海地区不同民族乙肝病毒基因分型及临床特点. 青海医药杂志, 2019, 49(1): 1-4.
15.	Zhang Q, Liao Y, Chen J, et al. Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China. Sci Rep, 2015, 5: 17413.
16.	吴泽刚, 李艳, 童永清. 武汉地区 263 例乙型肝炎患者 HBV 分型及耐药分析. 职业与健康, 2017, 33(19): 2718-2720.
17.	陈洪涛, 何桂蓉, 杨智, 等. 核苷 (酸) 类药物治疗慢性乙型肝炎的耐药突变分析. 新发传染病电子杂志, 2019, 4(1): 24-27.
18.	Cunha-Silva M, Marinho FRT, Oliveira PF, et al. Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors. Braz J Infect Dis, 2017, 21(4): 441-447.
19.	马蓉, 徐弘扬, 杨锡彤, 等. 大理地区乙肝患者基因分型及耐药突变相关分析. 世界最新医学信息文摘, 2019, 19(20): 1-3, 5.
20.	李少燕, 柳明波. 经治 HBV 感染者的 HBV 基因分型及其对核苷类药物的耐药情况. 广西医学, 2019, 41(4): 478-480.
21.	Li X, Liu Y, Xin S, et al. Comparison of detection rate and mutational pattern of drug-resistant mutations between a large cohort of genotype B and genotype C hepatitis B virus-infected patients in North China. Microb Drug Resist, 2017, 23(4): 516-522.
22.	Velkov S, Ott JJ, Protzer U, et al. The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes (Basel), 2018, 9(10): pii: E495.
23.	赵志军, 刘红玲, 钟利, 等. 宁夏地区慢性乙型肝炎患者乙肝病毒基因分型与耐药突变分析. 微循环学杂志, 2018, 28(4): 52-56, 66.
24.	许桂丹, 肖树荣, 王春芳, 等. 桂西地区 869 例慢性乙型肝炎病毒基因分型与耐药突变分析. 医学研究生学报, 2018, 31(11): 1163-1166.

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2015, 385(9963): 117-171.
2. 崔富强, 庄辉. 我国乙型肝炎防控工作进展、挑战及对策. 中国病毒病杂志, 2016(2): 81-87.
3. Liu CJ, Kao JH. Global perspective on the natural history of chronic hepatitis B: role of hepatitis B virus genotypes A to J. Semin Liver Dis, 2013, 33(2): 97-102.
4. Croagh CM, Desmond PV, Bell SJ. Genotypes and viral variantsin chronic hepatitis B: a review of epidemiology and clinical relevance. World J Hepatol, 2015, 7(3): 289-303.
5. 申静, 刘薇拉, 王菲. 太原地区乙肝病毒基因分型与临床指标的相关性分析. 中国卫生检验杂志, 2015, 25(14): 2383-2385.
6. 中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南 (2015 年版). 中华实验和临床感染病杂志 (电子版), 2015, 9(5): 570-589.
7. European Association for the Study of the Liver. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol, 2017, 67(2): 370-398.
8. Ott JJ, Stevens GA, Groeger J, et al. Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity. Vaccine, 2012, 30(12): 2212-2219.
9. Sugauchi F, Kumada H, Acharya SA, et al. Epidemiological and sequence differences between two subtypes (Ae and Aa) of hepatitis B virus genotype A. J Gen Virol, 2004, 85(Pt 4): 811-820.
10. Li HM, Wang JQ, Wang R, et al. Hepatitis B virus genotypes and genome characteristics in China. World J Gastroenterol, 2015, 21(21): 6684-6697.
11. Lin CL, Kao JH. The clinical implications of hepatitis B virus genotype: recent advances. J Gastroenterol Hepatol, 2011, 26(Suppl 1): 123-130.
12. Liu F, Chen L, Yu DM, et al. Evolutionary patterns of hepatitis B virus quasispecies under different selective pressures: correlation with antiviral efficacy. Gut, 2011, 60(9): 1269-1277.
13. 张爱民, 王慧芬, 王海滨, 等. 中国 30 个地区 HBV 基因型分布特点和临床意义. 中华实验和临床病毒学杂志, 2011, 25(2): 126-128.
14. 张嘉刚, 杨秀兰, 于国英. 青海地区不同民族乙肝病毒基因分型及临床特点. 青海医药杂志, 2019, 49(1): 1-4.
15. Zhang Q, Liao Y, Chen J, et al. Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China. Sci Rep, 2015, 5: 17413.
16. 吴泽刚, 李艳, 童永清. 武汉地区 263 例乙型肝炎患者 HBV 分型及耐药分析. 职业与健康, 2017, 33(19): 2718-2720.
17. 陈洪涛, 何桂蓉, 杨智, 等. 核苷 (酸) 类药物治疗慢性乙型肝炎的耐药突变分析. 新发传染病电子杂志, 2019, 4(1): 24-27.
18. Cunha-Silva M, Marinho FRT, Oliveira PF, et al. Retrospective analysis of hepatitis B virus chronic infection in 247 patients: clinical stages, response to treatment and poor prognostic factors. Braz J Infect Dis, 2017, 21(4): 441-447.
19. 马蓉, 徐弘扬, 杨锡彤, 等. 大理地区乙肝患者基因分型及耐药突变相关分析. 世界最新医学信息文摘, 2019, 19(20): 1-3, 5.
20. 李少燕, 柳明波. 经治 HBV 感染者的 HBV 基因分型及其对核苷类药物的耐药情况. 广西医学, 2019, 41(4): 478-480.
21. Li X, Liu Y, Xin S, et al. Comparison of detection rate and mutational pattern of drug-resistant mutations between a large cohort of genotype B and genotype C hepatitis B virus-infected patients in North China. Microb Drug Resist, 2017, 23(4): 516-522.
22. Velkov S, Ott JJ, Protzer U, et al. The global hepatitis B virus genotype distribution approximated from available genotyping data. Genes (Basel), 2018, 9(10): pii: E495.
23. 赵志军, 刘红玲, 钟利, 等. 宁夏地区慢性乙型肝炎患者乙肝病毒基因分型与耐药突变分析. 微循环学杂志, 2018, 28(4): 52-56, 66.
24. 许桂丹, 肖树荣, 王春芳, 等. 桂西地区 869 例慢性乙型肝炎病毒基因分型与耐药突变分析. 医学研究生学报, 2018, 31(11): 1163-1166.

West China Medical Journal

Genotyping and drug resistance mutation analysis of hepatitis B virus in chronic hepatitis B patients in West China Hospital

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