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戊型肝炎病毒感染重症化和慢性化的机制

陈俞心 王艺瑾

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戊型肝炎病毒感染重症化和慢性化的机制

DOI: 10.3969/j.issn.1001-5256.2023.11.003
利益冲突声明:本文不存在任何利益冲突。
作者贡献声明:‍陈俞心负责查阅文献,起草文章;王艺瑾负责拟定课题,设计写作思路,指导撰写文章并最后定稿。
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    通信作者:

    ‍王艺瑾, wangyj3@sustech.edu.cn (ORCID: 0000-0002-3700-1766)

The mechanism of the severe exacerbation and chronicity of hepatitis E virus infection

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  • 摘要: 戊型肝炎病毒(HEV)感染是全球范围急性病毒性肝炎最常见的原因。在过去十年,HEV被发现不仅能引起急性自限性疾病,还可导致重症及慢性感染。HEV感染孕妇或基础肝病患者后易发展为肝衰竭,病死率较高;HEV感染实体器官移植患者易发展为慢性肝炎。本文介绍了HEV重症及慢性感染的诊断、临床特征、传播方式、预防和治疗,重点探讨了HEV重症化和慢性化过程中免疫反应、炎症反应以及病毒本身的特征,并总结其促进HEV病程进展的机制。然而,现有研究与临床应用之间仍然存在鸿沟,目前仍然缺乏针对重症及慢性HEV的较好的诊疗方案。临床研究人员需要不断推进戊型肝炎发病机制及系统的队列研究,同时提高临床护理水平,最终实现预防和改善戊型肝炎患者预后的目标。

     

  • [1] MA JX, LIU YY, LI Q, et al. Study on the safety and immunogenicity of simultaneous vaccination on both hepatitis E and hepatitis B vaccines[J]. Chin J Epidemiol, 2019, 40( 4): 451- 456. DOI: 10.3760/cma.j.issn.0254-6450.2019.04.015.

    马建新, 刘瑶瑶, 李倩, 等. 戊型肝炎疫苗和乙型肝炎疫苗联合接种的安全性及免疫原性研究[J]. 中华流行病学杂志, 2019, 40( 4): 451- 456. DOI: 10.3760/cma.j.issn.0254-6450.2019.04.015.
    [2] HUANG AD, TANG L, WANG XQ, et al. Hepatitis E incidence trends and spatial-temporal clustering in China, 2011-2021[J]. Chin J Vaccines Immun, 2022, 28( 4): 417- 421. DOI: 10.19914/j.CJVI.2022080.

    黄澳迪, 唐林, 王晓琪, 等. 中国2011—2021年戊型病毒性肝炎发病趋势和时空聚集性[J]. 中国疫苗和免疫, 2022, 28( 4): 417- 421. DOI: 10.19914/j.CJVI.2022080.
    [3] WANG W, CHEN KY, WU LM, et al. Genetic characteristics of hepatitis E in Shanghai, 2017-2020[J]. Dis Surveillance, 2022, 37( 2): 214- 219. DOI: 10.3784/jbjc.202106210349.

    王葳, 陈恺韵, 吴立梦, 等. 2017—2020年上海市戊型肝炎病毒基因型特征研究[J]. 疾病监测, 2022, 37( 2): 214- 219. DOI: 10.3784/jbjc.202106210349.
    [4] NAIR VP, ANANG S, SUBRAMANI C, et al. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus[J]. PLoS Pathog, 2016, 12( 4): e1005521. DOI: 10.1371/journal.ppat.1005521.
    [5] PÉREZ-GRACIA MT, SUAY-GARCÍA B, MATEOS-LINDEMANN ML. Hepatitis E and pregnancy: Current state[J]. Rev Med Virol, 2017, 27( 3): e1929. DOI: 10.1002/rmv.1929.
    [6] LHOMME S, MARION O, ABRAVANEL F, et al. Clinical manifestations, pathogenesis and treatment of hepatitis E virus infections[J]. J Clin Med, 2020, 9( 2): 331. DOI: 10.3390/jcm9020331.
    [7] ZHOU XY, HUANG F, XU L, et al. Hepatitis E virus infects neurons and brains[J]. J Infect Dis, 2017, 215( 8): 1197- 1206. DOI: 10.1093/infdis/jix079.
    [8] WENTER C, BORENA W, OBERHUBER G, et al. Acute liver failure in immunocompetent patients infected with hepatitis E[J]. Wien Klin Wochenschr, 2019, 131( 17-18): 442- 445. DOI: 10.1007/s00508-019-01547-2.
    [9] WANG YJ, LIU SH, PAN QW, et al. Chronic hepatitis E in an immunocompetent patient[J]. Clin Res Hepatol Gastroenterol, 2020, 44( 3): e66- e68. DOI: 10.1016/j.clinre.2019.08.001.
    [10] DALTON HR, STABLEFORTH W, THURAIRAJAH P, et al. Autochthonous hepatitis E in Southwest England: Natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease[J]. Eur J Gastroenterol Hepatol, 2008, 20( 8): 784- 790. DOI: 10.1097/MEG.0b013e3282f5195a.
    [11] LI JX, LI YQ, LI J. Clinical analysis for 46 hepatitis E cases in elderly people[J]. Med J Chin People’s Heath, 2010, 22( 16): 2064- 2065. DOI: 10.3969/j.issn.1672-0369.2010.16.012.

    李君熹, 李玉琴, 李晶. 老年戊型病毒性肝炎46例临床分析[J]. 中国民康医学, 2010, 22( 16): 2064- 2065. DOI: 10.3969/j.issn.1672-0369.2010.16.012.
    [12] MA XX, JI YP, JIN L, et al. Prevalence and clinical features of hepatitis E virus infection in pregnant women: A large cohort study in Inner Mongolia, China[J]. Clin Res Hepatol Gastroenterol, 2021, 45( 4): 101536. DOI: 10.1016/j.clinre.2020.08.012.
    [13] RAYIS DA, JUMAA AM, GASIM GI, et al. An outbreak of hepatitis E and high maternal mortality at Port Sudan, Eastern Sudan[J]. Pathog Glob Health, 2013, 107( 2): 66- 68. DOI: 10.1179/2047773213Y.0000000076.
    [14] QIAN ZY, LI TY, XIA YP, et al. Genotype 4 hepatitis E virus replicates in the placenta, causes severe histopathological damage, and vertically transmits to fetuses[J]. J Infect, 2023, 87( 1): 34- 45. DOI: 10.1016/j.jinf.2023.05.003.
    [15] WANG YJ, LIU HY, JIANG YY, et al. Poor outcomes of acute hepatitis E in patients with cirrhotic liver diseases regardless of etiology[J]. Open Forum Infect Dis, 2020, 7( 4): ofaa107. DOI: 10.1093/ofid/ofaa107.
    [16] WANG YJ, LIU HY, LIU SH, et al. Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case-control study[J]. Liver Int, 2019, 39( 12): 2291- 2300. DOI: 10.1111/liv.14221.
    [17] KUMAR A, SARASWAT VA. Hepatitis E and acute-on-chronic liver failure[J]. J Clin Exp Hepatol, 2013, 3( 3): 225- 230. DOI: 10.1016/j.jceh.2013.08.013.
    [18] FRIAS M, LÓPEZ-LÓPEZ P, RIVERO A, et al. Role of hepatitis E virus infection in acute-on-chronic liver failure[J]. Biomed Res Int, 2018, 2018: 9098535. DOI: 10.1155/2018/9098535.
    [19] KUMAR ACHARYA S, KUMAR SHARMA P, SINGH R, et al. Hepatitis E virus(HEV) infection in patients with cirrhosis is associated with rapid decompensation and death[J]. J Hepatol, 2007, 46( 3): 387- 394. DOI: 10.1016/j.jhep.2006.09.016.
    [20] FANG L, ZHANG JL, CHEN HY, et al. Epidemiological characteristics and clinical manifestations of hepatitis E in a tertiary hospital in China: A retrospective study[J]. Front Microbiol, 2022, 12: 831968. DOI: 10.3389/fmicb.2021.831968.
    [21] KAMAR N, ROSTAING L, LEGRAND-ABRAVANEL F, et al. How should hepatitis E virus infection be defined in organ-transplant recipients?[J]. Am J Transplant, 2013, 13( 7): 1935- 1936. DOI: 10.1111/ajt.12253.
    [22] von FELDEN J, ALRIC L, PISCHKE S, et al. The burden of hepatitis E among patients with haematological malignancies: A retrospective European cohort study[J]. J Hepatol, 2019, 71( 3): 465- 472. DOI: 10.1016/j.jhep.2019.04.022.
    [23] DI BARTOLOMEO S, CARUBBI F, CIPRIANI P. Hepatitis E virus and rheumatic diseases: What do rheumatologists need to know?[J]. BMC Rheumatol, 2020, 4: 51. DOI: 10.1186/s41927-020-00149-0.
    [24] MA ZR, de MAN RA, KAMAR N, et al. Chronic hepatitis E: Advancing research and patient care[J]. J Hepatol, 2022, 77( 4): 1109- 1123. DOI: 10.1016/j.jhep.2022.05.006.
    [25] DALTON HR, BENDALL RP, KEANE FE, et al. Persistent carriage of hepatitis E virus in patients with HIV infection[J]. N Engl J Med, 2009, 361( 10): 1025- 1027. DOI: 10.1056/NEJMc0903778.
    [26] PRABHU SB, GUPTA P, DURGAPAL H, et al. Study of cellular immune response against Hepatitis E virus(HEV)[J]. J Viral Hepat, 2011, 18( 8): 587- 594. DOI: 10.1111/j.1365-2893.2010.01338.x.
    [27] NAIK A, GOEL A, AGRAWAL V, et al. Changes in gene expression in liver tissue from patients with fulminant hepatitis E[J]. World J Gastroenterol, 2015, 21( 26): 8032- 8042. DOI: 10.3748/wjg.v21.i26.8032.
    [28] KRAIN LJ, NELSON KE, LABRIQUE AB. Host immune status and response to hepatitis E virus infection[J]. Clin Microbiol Rev, 2014, 27( 1): 139- 165. DOI: 10.1128/CMR.00062-13.
    [29] DAVIS MM, BJORKMAN PJ. T-cell antigen receptor genes and T-cell recognition[J]. Nature, 1988, 334( 6181): 395- 402. DOI: 10.1038/334395a0.
    [30] LUCKHEERAM RV, ZHOU R, VERMA AD, et al. CD4⁺T cells: Differentiation and functions[J]. Clin Dev Immunol, 2012, 2012: 925135. DOI: 10.1155/2012/925135.
    [31] WU J, GUO YR, LU X, et al. Th1/Th2 cells and associated cytokines in acute hepatitis E and related acute liver failure[J]. J Immunol Res, 2020, 2020: 6027361. DOI: 10.1155/2020/6027361.
    [32] SRIVASTAVA R, AGGARWAL R, JAMEEL S, et al. Cellular immune responses in acute hepatitis E virus infection to the viral open reading frame 2 protein[J]. Viral Immunol, 2007, 20( 1): 56- 65. DOI: 10.1089/vim.2006.0053.
    [33] SRIVASTAVA R, AGGARWAL R, SACHDEVA S, et al. Adaptive immune responses during acute uncomplicated and fulminant hepatitis E[J]. J Gastroenterol Hepatol, 2011, 26( 2): 306- 311. DOI: 10.1111/j.1440-1746.2010.06356.x.
    [34] WU J, LING B, GUO NZ, et al. Immunological manifestations of hepatitis E-associated acute and chronic liver failure and its regulatory mechanisms[J]. Front Med, 2021, 8: 725993. DOI: 10.3389/fmed.2021.725993.
    [35] WANG WS, XU L, BRANDSMA JH, et al. Convergent transcription of interferon-stimulated genes by TNF-α and IFN-α augments antiviral activity against HCV and HEV[J]. Sci Rep, 2016, 6: 25482. DOI: 10.1038/srep25482.
    [36] LI Y, YU PF, KESSLER AL, et al. Hepatitis E virus infection activates NOD-like receptor family pyrin domain-containing 3 inflammasome antagonizing interferon response but therapeutically targetable[J]. Hepatology, 2022, 75( 1): 196- 212. DOI: 10.1002/hep.32114.
    [37] WU J, ZHANG XY, LIU HY, et al. RDW, NLR and RLR in predicting liver failure and prognosis in patients with hepatitis E virus infection[J]. Clin Biochem, 2019, 63: 24- 31. DOI: 10.1016/j.clinbiochem.2018.11.012.
    [38] MUNOZ-SUANO A, HAMILTON AB, BETZ AG. Gimme shelter: The immune system during pregnancy[J]. Immunol Rev, 2011, 241( 1): 20- 38. DOI: 10.1111/j.1600-065X.2011.01002.x.
    [39] SARGENT IL, BORZYCHOWSKI AM, REDMAN CWG. NK cells and human pregnancy: An inflammatory view[J]. Trends Immunol, 2006, 27( 9): 399- 404. DOI: 10.1016/j.it.2006.06.009.
    [40] YU WH, HAO XH, LI Y, et al. Vertical transmission of hepatitis E virus in pregnant rhesus macaques[J]. Sci Rep, 2020, 10( 1): 17517. DOI: 10.1038/s41598-020-74461-7.
    [41] XU L, WANG WS, LI YL, et al. RIG-I is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production[J]. Hepatology, 2017, 65( 6): 1823- 1839. DOI: 10.1002/hep.29105.
    [42] WANG WS, WANG YJ, QU CB, et al. The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response[J]. Hepatology, 2018, 67( 6): 2096- 2112. DOI: 10.1002/hep.29702.
    [43] SEHGAL R, PATRA S, DAVID P, et al. Impaired monocyte-macrophage functions and defective Toll-like receptor signaling in hepatitis E virus-infected pregnant women with acute liver failure[J]. Hepatology, 2015, 62( 6): 1683- 1696. DOI: 10.1002/hep.28143.
    [44] JILANI N, DAS BC, HUSAIN SA, et al. Hepatitis E virus infection and fulminant hepatic failure during pregnancy[J]. J Gastroenterol Hepatol, 2007, 22( 5): 676- 682. DOI: 10.1111/j.1440-1746.2007.04913.x.
    [45] KUMAR A, DEVI SG, KAR P, et al. Association of cytokines in hepatitis E with pregnancy outcome[J]. Cytokine, 2014, 65( 1): 95- 104. DOI: 10.1016/j.cyto.2013.09.022.
    [46] SINGH S, DAGA MK, KUMAR A, et al. Role of oestrogen and its receptors in HEV-associated feto-maternal outcomes[J]. Liver Int, 2019, 39( 4): 633- 639. DOI: 10.1111/liv.13928.
    [47] PAL R, AGGARWAL R, NAIK SR, et al. Immunological alterations in pregnant women with acute hepatitis E[J]. J Gastroenterol Hepatol, 2005, 20( 7): 1094- 1101. DOI: 10.1111/j.1440-1746.2005.03875.x.
    [48] YANG C, YU W, BI Y, et al. Increased oestradiol in hepatitis E virus-infected pregnant women promotes viral replication[J]. J Viral Hepat, 2018, 25( 6): 742- 751. DOI: 10.1111/jvh.12865.
    [49] ZHOU XY, WANG YJ, METSELAAR HJ, et al. Rapamycin and everolimus facilitate hepatitis E virus replication: Revealing a basal defense mechanism of PI3K-PKB-mTOR pathway[J]. J Hepatol, 2014, 61( 4): 746- 754. DOI: 10.1016/j.jhep.2014.05.026.
    [50] BI YH, YANG CC, YU WH, et al. Pregnancy serum facilitates hepatitis E virus replication in vitro[J]. J Gen Virol, 2015, 96( Pt 5): 1055- 1061. DOI: 10.1099/vir.0.000054.
    [51] HE YJ, WANG F, YAO NJ, et al. Serum superoxide dismutase level is a potential biomarker of disease prognosis in patients with HEV-induced liver failure[J]. BMC Gastroenterol, 2022, 22( 1): 14. DOI: 10.1186/s12876-022-02095-2.
    [52] EL-MOKHTAR MA, OTHMAN ER, KHASHBAH MY, et al. Evidence of the extrahepatic replication of hepatitis E virus in human endometrial stromal cells[J]. Pathogens, 2020, 9( 4): 295. DOI: 10.3390/pathogens9040295.
    [53] GOUILLY J, CHEN Q, SIEWIERA J, et al. Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface[J]. Nat Commun, 2018, 9( 1): 4748. DOI: 10.1038/s41467-018-07200-2.
    [54] YADAV KK, BOLEY PA, FRITTS Z, et al. Ectopic expression of genotype 1 hepatitis E virus ORF4 increases genotype 3 HEV viral replication in cell culture[J]. Viruses, 2021, 13( 1): 75. DOI: 10.3390/v13010075.
    [55] BORKAKOTI J, AHMED G, RAI A, et al. Report of novel H105R, D29N, V27A mutations in the methyltransferase region of the HEV genome in patients with acute liver failure[J]. J Clin Virol, 2017, 91: 1- 4. DOI: 10.1016/j.jcv.2017.03.017.
    [56] TAKAHASHI K, OKAMOTO H, ABE N, et al. Virulent strain of hepatitis E virus genotype 3, Japan[J]. Emerg Infect Dis, 2009, 15( 5): 704- 709. DOI: 10.3201/eid1505.081100.
    [57] KAMAR N, SELVES J, MANSUY JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients[J]. N Engl J Med, 2008, 358( 8): 811- 817. DOI: 10.1056/nejmoa0706992.
    [58] WANG YJ, CHEN GF, PAN QW, et al. Chronic hepatitis E in a renal transplant recipient: The first report of genotype 4 hepatitis E virus caused chronic infection in organ recipient[J]. Gastroenterology, 2018, 154( 4): 1199- 1201. DOI: 10.1053/j.gastro.2017.12.028.
    [59] KAMAR N, MANSUY JM, COINTAULT O, et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients[J]. Am J Transplant, 2008, 8( 8): 1744- 1748. DOI: 10.1111/j.1600-6143.2008.02286.x.
    [60] WANG YJ, METSELAAR HJ, PEPPELENBOSCH MP, et al. Chronic hepatitis E in solid-organ transplantation: The key implications of immunosuppressants[J]. Curr Opin Infect Dis, 2014, 27( 4): 303- 308. DOI: 10.1097/QCO.0000000000000074.
    [61] BREMER W, BLASCZYK H, YIN X, et al. Resolution of hepatitis E virus infection in CD8+ T cell-depleted rhesus macaques[J]. J Hepatol, 2021, 75( 3): 557- 564. DOI: 10.1016/j.jhep.2021.04.036.
    [62] SUNEETHA PV, PISCHKE S, SCHLAPHOFF V, et al. Hepatitis E virus(HEV)-specific T-cell responses are associated with control of HEV infection[J]. Hepatology, 2012, 55( 3): 695- 708. DOI: 10.1002/hep.24738.
    [63] WANG YJ, ZHOU XY, DEBING Y, et al. Calcineurin inhibitors stimulate and mycophenolic acid inhibits replication of hepatitis E virus[J]. Gastroenterology, 2014, 146( 7): 1775- 1783. DOI: 10.1053/j.gastro.2014.02.036.
    [64] PISCHKE S, STIEFEL P, FRANZ B, et al. Chronic hepatitis e in heart transplant recipients[J]. Am J Transplant, 2012, 12( 11): 3128- 3133. DOI: 10.1111/j.1600-6143.2012.04200.x.
    [65] ZHOU XY, de MAN RA, de KNEGT RJ, et al. Epidemiology and management of chronic hepatitis E infection in solid organ transplantation: A comprehensive literature review[J]. Rev Med Virol, 2013, 23( 5): 295- 304. DOI: 10.1002/rmv.1751.
    [66] NGUYEN HT, TORIAN U, FAULK K, et al. A naturally occurring human/hepatitis E recombinant virus predominates in serum but not in faeces of a chronic hepatitis E patient and has a growth advantage in cell culture[J]. J Gen Virol, 2012, 93( Pt 3): 526- 530. DOI: 10.1099/vir.0.037259-0.
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