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.	崔富強, 莊輝. 我國乙型肝炎防控工作進展、挑戰及對策. 中國病毒病雜志, 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.	申靜, 劉薇拉, 王菲. 太原地區乙肝病毒基因分型與臨床指標的相關性分析. 中國衛生檢驗雜志, 2015, 25(14): 2383-2385.
6.	中華醫學會肝病學分會, 中華醫學會感染病學分會. 慢性乙型肝炎防治指南 (2015 年版). 中華實驗和臨床感染病雜志 (電子版), 2015, 9(5): 570-589.
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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.
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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.	張愛民, 王慧芬, 王海濱, 等. 中國 30 個地區 HBV 基因型分布特點和臨床意義. 中華實驗和臨床病毒學雜志, 2011, 25(2): 126-128.
14.	張嘉剛, 楊秀蘭, 于國英. 青海地區不同民族乙肝病毒基因分型及臨床特點. 青海醫藥雜志, 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.	吳澤剛, 李艷, 童永清. 武漢地區 263 例乙型肝炎患者 HBV 分型及耐藥分析. 職業與健康, 2017, 33(19): 2718-2720.
17.	陳洪濤, 何桂蓉, 楊智, 等. 核苷 (酸) 類藥物治療慢性乙型肝炎的耐藥突變分析. 新發傳染病電子雜志, 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.	馬蓉, 徐弘揚, 楊錫彤, 等. 大理地區乙肝患者基因分型及耐藥突變相關分析. 世界最新醫學信息文摘, 2019, 19(20): 1-3, 5.
20.	李少燕, 柳明波. 經治 HBV 感染者的 HBV 基因分型及其對核苷類藥物的耐藥情況. 廣西醫學, 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.	趙志軍, 劉紅玲, 鐘利, 等. 寧夏地區慢性乙型肝炎患者乙肝病毒基因分型與耐藥突變分析. 微循環學雜志, 2018, 28(4): 52-56, 66.
24.	許桂丹, 肖樹榮, 王春芳, 等. 桂西地區 869 例慢性乙型肝炎病毒基因分型與耐藥突變分析. 醫學研究生學報, 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. 崔富強, 莊輝. 我國乙型肝炎防控工作進展、挑戰及對策. 中國病毒病雜志, 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. 申靜, 劉薇拉, 王菲. 太原地區乙肝病毒基因分型與臨床指標的相關性分析. 中國衛生檢驗雜志, 2015, 25(14): 2383-2385.
6. 中華醫學會肝病學分會, 中華醫學會感染病學分會. 慢性乙型肝炎防治指南 (2015 年版). 中華實驗和臨床感染病雜志 (電子版), 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. 張愛民, 王慧芬, 王海濱, 等. 中國 30 個地區 HBV 基因型分布特點和臨床意義. 中華實驗和臨床病毒學雜志, 2011, 25(2): 126-128.
14. 張嘉剛, 楊秀蘭, 于國英. 青海地區不同民族乙肝病毒基因分型及臨床特點. 青海醫藥雜志, 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. 吳澤剛, 李艷, 童永清. 武漢地區 263 例乙型肝炎患者 HBV 分型及耐藥分析. 職業與健康, 2017, 33(19): 2718-2720.
17. 陳洪濤, 何桂蓉, 楊智, 等. 核苷 (酸) 類藥物治療慢性乙型肝炎的耐藥突變分析. 新發傳染病電子雜志, 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. 馬蓉, 徐弘揚, 楊錫彤, 等. 大理地區乙肝患者基因分型及耐藥突變相關分析. 世界最新醫學信息文摘, 2019, 19(20): 1-3, 5.
20. 李少燕, 柳明波. 經治 HBV 感染者的 HBV 基因分型及其對核苷類藥物的耐藥情況. 廣西醫學, 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. 趙志軍, 劉紅玲, 鐘利, 等. 寧夏地區慢性乙型肝炎患者乙肝病毒基因分型與耐藥突變分析. 微循環學雜志, 2018, 28(4): 52-56, 66.
24. 許桂丹, 肖樹榮, 王春芳, 等. 桂西地區 869 例慢性乙型肝炎病毒基因分型與耐藥突變分析. 醫學研究生學報, 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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