乙型肝炎病毒的分子流行病学研究进展

摘要/Abstract

摘要： 乙型肝炎病毒（HBV）的分子流行病学近年来一直是HBV基础和临床研究方面的热点问题。本文总结了近20年来国内外HBV的感染流行特点,分析了HBV基因型/亚型的地域性分布特征,阐述了HBV基因型的临床意义,解析了HBV基因型对抗病毒应答效应的影响。这些HBV分子流行病学方面的研究将有助于高耐药屏障的抗乙肝病毒药物的研发,有助于HBV感染诱发的各种肝脏相关疾病的精准治疗。

关键词: 乙型肝炎病毒, 基因型, 分子流行病学

Abstract: The molecular epidemiology of hepatitis B virus (HBV) has been a hot issue in the basic and clinical research of HBV in recent years. This article summarizes the national and international epidemic characteristics of HBV infection in the past two decades, analyzes the regional distribution characteristics of HBV genotypes/subtypes, elaborates the clinical significance of HBV genotypes, and analyzes the effect of HBV genotypes on the antiviral response. These HBV molecular epidemiological studies will help the development of anti-HBV drugs with high drug resistance barriers, and support the precise treatment of various liver-related diseases induced by HBV infection.

Key words: Hepatitis B virus, Genotype, Molecular epidemiology

易永祥. 乙型肝炎病毒的分子流行病学研究进展[J]. 新发传染病电子杂志, 2020, 5(1): 1-7.

Yi Yongxiang. Research progress in molecular epidemiology of hepatitis B virus[J]. Electronic Journal of Emerging Infectious Diseases, 2020, 5(1): 1-7.

参考文献

[1] Trépo C, Chan HL, Lok A.Hepatitis B virus infection[J]. Lancet, 2014, 384(9959):2053-2063.
[2] WHO.Global hepatitis report,2017[EB/OL]. http://publications/global hepatitis-report 2017/en/.
[3] WHO. Global health sector strategy on viral hepatitis 2016-2021[EB/OL]. [2019-02-15]. http://www.who.int/hepatitis/strategy2016-2021/ghss-hep/en/.
[4] 刘珏, 刘民. 我国实现WHO 2030消除乙型肝炎目标的进展与挑战[J]. 中华流行病学杂志, 2019, 40(6):605-609.
[5] Schweitzer A, Horn J, Mikolajczyk RT, et al.Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013[J]. Lancet, 2015, 386(10003):1546-1555.
[6] Ott JJ, Stevens GA, Groeger J, et al.Global epidemiology of hepatitis B virus infection: new estimates of age-specific HBsAg seroprevalence and endemicity[J]. Vaccine, 2012, 30(12):2212-2219.
[7] MacLachlan JH, Cowie BC. Hepatitis B virus epidemiology[J]. Cold Spring Harb Perspect Med, 2015, 5(5):a021410.
[8] Matthews PC, Beloukas A, Malik A, et al.Prevalence and characteristics of hepatitis B virus (HBV) coinfection among HIV-positive women in South Africa and Botswana[J]. PLoS One, 2015, 10(7):e0134037.
[9] Wang H, Men P, Xiao Y, et al.Hepatitis B infection in the general population of China: a systematic review and meta-analysis[J]. BMC Infect Dis, 2019, 19(811):1-10.
[10] Gish RG, Bui TD, Nguyen CT, et al.Liver disease in Vietnam: screening, surveillance, management and education: a 5-year plan and call to action[J]. J Gastroenterol Hepatol,2012, 27(2):238-247.
[11] Nguyen VT, McLaws ML, Dore GJ, et al. Highly endemic hepatitis B infection in rural Vietnam[J]. J Gastroenterol Hepatol, 2007, 22(12):2093-2100.
[12] Gish RG, Cohen CA, Block JM, et al.Data supporting updating estimates of the prevalence of chronic hepatitis B and C in the United States[J]. Hepatology, 2015, 62(5):1339-1341.
[13] Amy S, Tang MD, Janice Lyu, et al.Disparities in hepatitis B virus infection and immunity among New York City Asian American Patients, 1997 to 2017[J]. Am J Public Health, 2018, 108(S4): S327-S335.
[14] Kowdley KV, Wang CC, Welch S, et al.Prevalence of chronic hepatitis B among foreign-born persons living in the United States by country of origin[J]. Hepatology, 2012, 56(2):422-423.
[15] Cui F, Shen L, Li L, et al.Prevention of chronic hepatitis B after 3 decades of escalating vaccination policy, China[J]. Emerg Infect Dis, 2017,23(5):765-772.
[16] 蔡大川,任红. 40年风雨历程:中国乙型肝炎的负担和希望[J]. 中国肝脏病杂志, 2019, 27(1):3-6.
[17] Zeng F, Guo P, Huang Y, et al.Epidemiology of hepatitis B virus infection: results from a community-based study of 0.15 million residents in South China[J]. Sci Rep, 2016, 6(36186):1-16.
[18] Zhu Q, Shao X, Chen S, et al.Epidemiological serosurvey of hepatitis B virus among children aged 1-14 years in Guangdong Province, China[J]. Int J Infect Dis, 2018, 71:25-29.
[19] Jing M, Xu H, Sui DM, et al.A retrospective serological survey of hepatitis B virus infection in Northeast China[J]. BMC Infect Dis, 2019, 19(1):440.
[20] Knipe DM, Howley PM.Fields virology[M]. Vol 2, 6th ed. Philadelphia: Lippincott Williams & Wilkins, 2013: 2185-2221.
[21] Shepard CW, Simard EP, Finelli L, et al.Hepatitis B virus infection: epidemiology and vaccination[J]. Epidemiol Rev, 2006, 28(1):112-125.
[22] MacKellar DA, Valleroy LA, Secura GM, et al. Two decades after vaccine license: hepatitis B immunization and infection among young men who have sex with men[J]. Am J Public Health,2001, 91(6):965-971.
[23] Levine OS, Vlahov D, Nelson KE.Epidemiology of hepatitis B virus infections among injecting drug users: seroprevalence, risk factors, and viral interactions[J]. Epidemiol Rev, 1994, 16(2):418-436.
[24] Velkov S, Ott J, Protzer U.The global hepatitis B virus genotype distribution approximated from available genotyping data[J]. Genes, 2018, 495(9):1-14.
[25] Kramvis A.Genotypes and genetic variability of hepatitis B virus[J]. Intervirology, 2014, 57(3-4):141-150.
[26] Pourkarim MR,Amini-Bavil-Olyaee S,Kurbanov F, et al. Molecular identification of hepatitis B virus genotypes/subgenotypes: revised classification hurdles and updated resolutions[J]. World J Gastroenterol, 2014, 20(23):7152-7168.
[27] Kramvis A, Kew M, Francois G.Recent advances in the research of hepatitis B virus-related hepatocellular carcinoma: epidemiologic and molecular biological aspects[J]. Vaccine, 2005, 23(19): 2409-2423.
[28] Hübschen JM, Mbah PO, Forbi JC, et al.Detection of a new subgenotype of hepatitis B virus genotype A in Cameroon but not in neighbouring Nigeria[J]. Clin Microbiol Infect,2011, 17(1):88-94.
[29] Pourkarim MR, Amini-Bavil-Olyaee S, Lemey P, et al. HBV subgenotype misclassification expands quasi-subgenotype A3[J]. Clin Microbiol Infect, 2011, 17(6):947-949.
[30] Kramvis A, Paraskevis D.Subgenotype A1 of HBV-tracing human migrations in and out of Africa[J]. Antivir Ther, 2013, 18(3 Pt B):513-521.
[31] Shi W, Zhu C, Zheng W, et al.Subgenotype reclassification of genotype B hepatitis B virus[J]. BMC Gastroenterol, 2012, 12:116.
[32] Sugauchi F, Orito E, Ichida T, et al.Hepatitis B virus of genotype B with or without recombination with genotype C over the precure region plus the core gene[J]. J Virol, 2002, 76(12):5985-5992.
[33] Matsuo J, Do SH, Yamamoto C, et al.Clustering infection of hepatitis B virus genotype B4 among residents in Vietnam, and its genomic characters both intra- and extra-family[J]. PLoS One, 2017, 12(7):e0177248.
[34] Sakamoto T, Tanaka Y, Simonetti J, et al.Classification of hepatitis B virus genotype B into 2 major types based on characterization of a novel subgenotype in Arctic indigenous populations[J]. J Infect Dis, 2007, 196(10):1487-1492.
[35] Osiowy C, Larke B, Giles E.Distinct geographical and demographic distribution of hepatitis B virus genotypes in the Canadian Arctic as revealed through an extensive molecular epidemiological survey[J]. J Viral Hepat, 2011, 18(4):e11-e19.
[36] Mulyanto, Pancawardani P, Depamede SN, et al. Identification of four novel subgenotypes (C13-C16) and two inter-genotypic recombinants (C12/G and C13/B3) of hepatitis B virus in Papua province, Indonesia[J]. Virus Res, 2012, 163(1):129-140.
[37] Schulz TR, Edwards R, Thurnheer MC, et al.Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance[J]. J Med Virol, 2017,90(2):1-6.
[38] Davies J, Littlejohn M, Locarnini SA, et al.Molecular epidemiology of hepatitis B in the indigenous people of northern Australia[J]. J Gastroenterol Hepatol, 2013, 28(7):1234-1241.
[39] Ozaras R, Balkan II, Yemisen M, et al.Epidemiology of HBV subgenotypes D[J]. Clin Res Hepatol Gastroenterol, 2015, 39(1):28-37.
[40] Kosei H, Kouichi M, Yoshinari T, et al.A 79-year-old woman with acute hepatitis B caused by the infection of subgenotype D1 hepatitis B virus in Japan: a case study[J]. Intern Med, 2018, 57(21):3099-3104.
[41] Yousif M, Kramvis A.Genotype D of hepatitis B virus and its subgenotypes: an update[J]. Hepatol Res, 2013, 43(4):355-364.
[42] Hundie GB, Stalin RajV, Gebre Michael D, et al. A novel hepatitis B virus subgenotype D10 circulating in Ethiopia[J]. J Viral Hepat, 2017, 24(2):163-173.
[43] Andernach IE, Hunewald OE, Muller CP.Bayesian inference of the evolution of HBV/E[J]. PLoS One, 2013, 8(11):e81690.
[44] Kato H, Fujiwara K, Gish RG, et al.Classifying genotype F of hepatitis B virus into F1 and F2 subtypes[J]. World J Gastroenterol, 2005, 11(40):6295-6304.
[45] Panduro A, Maldonado-Gonzalez M, Fierro NA, et al.Distribution of HBV genotypes F and H in Mexico and Central America[J]. Antivir Ther, 2013, 18(3 Pt B):475-484.
[46] Alvarado-Mora MV, Botelho-Lima LS, Santana RA,et al.Distribution of hepatitis B virus subgenotype F2a in São Paulo, Brazil[J]. BMC Res Notes, 2013, 6(1):423.
[47] Fragoso-Fonseca DE, Escobar-Escamilla N, Lloret Y Sánchez LT, et al. Full genome and phylogenetic analysis of hepatitis B virus genotype F in Mexican isolates[J]. Arch Virol, 2018, 163(7):1981-1984.
[48] Lindh M.HBV genotype G -an odd genotype of unknown origin[J]. J Clin Virol, 2005, 34(4):315-316.
[49] Roman S, Panduro A.HBV endemicity in Mexico is associated with HBV genotypes H and G[J]. World J Gastroenterol, 2013, 19(33):5446-5453.
[50] Huy TT, Trinh TN, Abe K.New complex recombinant genotype of hepatitis B virus identified in Vietnam[J]. J Virol, 2008, 82(11):5657-5663.
[51] Arankalle VA, Gandhe SS, Borkakoty BJ, et al.A novel HBV recombinant (genotype I) similar to Vietnam/Laos in a primitive tribe in eastern India[J]. J Viral Hepat, 2010, 17(7):501-510.
[52] Osiowy C, Kaita K, Solar K, et al.Molecular characterization of hepatitis B virus and a 9-year clinical profile in a patient infected with genotype I[J]. J Med Virol, 2010, 82(6):942-948.
[53] Shen T, Yan XM, Liu HX, et al.Genotype I of hepatitis B virus was found in east Xishuangbanna, China and molecular dynamics of HBV/I[J]. J Viral Hepat, 2015, 22(1):37-45.
[54] Li GJ, Hue S, Harrison TJ, et al.Hepatitis B virus candidate subgenotype I1 varies in distribution throughout Guangxi, China and may have originated in Long An county, Guangxi[J]. J Med Virol, 2013, 85(5):799-807.
[55] Tatematsu K, Tanaka Y, Kurbanov F, et al.A genetic variant of hepatitis B virus divergent from known human and ape genotypes isolated from a Japanese patient and provisionally assigned to new genotype [J][J]. J Virol, 2009, 83(20):10538-10547.
[56] Tao J, Zhang W, Yue H, et al.Prevalence of Hepatitis B Virus Infection in Shenzhen, China, 2015-2018[J]. Sci Rep, 2019, 9(1):13948.
[57] Wang Z, Tanaka Y, Huang Y, et al.Clinical and virological characteristics of hepatitis B virus subgenotypes Ba, C1, and C2 in China[J]. J Clin Microbiol, 2007, 45(5):1491-1496.
[58] Yu R, Fan R, Hou J.Chronic hepatitis B virus infection: epidemiology, prevention, and treatment in China[J]. Front Med, 2014, 8(2):135-144.
[59] Ding Y, Sheng Q, Ma L, et al.Chronic HBV infection among pregnant women and their infants in Shenyang, China[J]. 2013, 7(10):17.
[60] Li XD, Wang L, Liu Y, et al.Characterization of hepatitis B virus genotypes/subgenotypes in 1,301 patients with chronic hepatitis B in North China[J]. Chin Med J, 2011, 124(24):4178-4183.
[61] Zhang Q, Liao Y, Chen J, et al.Epidemiology study of HBV genotypes and antiviral drug resistance in multi-ethnic regions from Western China[J]. Sci Rep, 2015,5:17413.
[62] Li H, She Q, Liu Y, et al.Clinical implication and viral mutation in basal core promoter/pre-core of hepatitis B virus C/D recombinant[J]. Hepatol Int, 2018, 12(5):447-455.
[63] Yanag Y, Du D, Jin L, et al.A molecular epidemiology study investigating familial clustering of hepatitis B virus infection in families with unfavorable prognoses in Northwest China[J]. J Med Virol, 2017, 89(8):1427-1434.
[64] Chen X, Dai B, Liu Z, et al.A novel B/C inter-genotype recombinant of hepatitis B virus identified in north-west China[J]. J Gen Virol, 2014 , 95(Pt 1):153-155.
[65] Shen L, Yin W, Zheng H, et al.Molecular epidemiological study of hepatitis B virus genotypes in Southwest, China[J]. J Med Virol, 2014, 86(8):1307e13.
[66] Lin CL, Kao JH.Hepatitis B virus genotypes and variants[J]. Cold Spring Harb Pers pect Med, 2015, 5(5):a021436.
[67] Kao JH, Chen PJ, Chen DS,et al.Recent advances in the research of hepatitis B virus-related hepatocellular carcinoma: epidemiologic and molecular biological aspects[J]. Adv Cancer Res, 2010, 108:21-72.
[68] Vutien P, Trinh HN, Nguyen K, et al.Precore and basal core promoter mutations in Asian American patients with hepatitis B e antigen-positive chronic hepatitis B[J]. Aliment Pharmacol Ther, 2013, 37(4):464-472.
[69] Tseng TC, Liu CJ, Yang HC, et al.High levels of hepatitis B surface antigen increase risk of hepatocellular carcinoma in patients with low HBV load[J]. Gastroenterology, 2012, 142(5):1140-1149.
[70] Yin J, Zhang H, Li C, et al.Role of hepatitis B virus genotype mixture, subgenotypes C2 and B2 on hepatocellular carcinoma: Compared with chronic hepatitis B and asymptomatic carrier state in the same area[J]. Carcinogenesis, 2008, 29(9):1685-1691.
[71] Wu JC, Huang YH, Chau GY, et al.Risk factors for early and late recurrence in hepatitis B-related hepatocellular carcinoma[J]. J Hepatol, 2009, 51(5):890-897.
[72] Livingston SE, Simonetti J, McMahon B, et al. Hepatitis B virus genotypes in Alaska native people with hepatocellular carcinoma: Preponderance of genotype F[J]. J Infect Dis, 2007, 195(1):5-11.
[73] Erhardt A, Blondin D, Hauck K, et al.Response to interferon a is hepatitis B virus genotype dependent: Genotype A is more sensitive to interferon than genotype D[J]. Gut, 2005, 54(7):1009-1013.
[74] Flink HJ, van Zonneveld M, Hansen BE, et al. HBV treatment with Peg-interferon a-2b for HBeAg-positive chronic hepatitis B: HBsAg loss is associated with HBV genotype[J]. Am J Gastroenterol, 2006, 101(2):297-303.
[75] Wiegand J, Hasenclever D, Tillmann HL.Should treatment of hepatitis B depend on hepatitis B virus genotypes? A hypothesis generated from an explorative analysis of published evidence[J]. Antivir Ther, 2008, 13(2):211-220.
[76] Hsieh TH, Tseng TC, Liu CJ, et al.Hepatitis B virus genotype B has an earlier emergence of lamivudine resistance than genotype C[J]. Antivir Ther, 2009, 14(8):1157-1163.
[77] Heathcote EJ, Marcellin P, Buti M, et al.Three-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B[J]. Gastroenterology, 2011, 140(1):132-143.