丁型肝炎研究进展
DOI: 10.3969/j.issn.1001-5256.2022.03.032
利益冲突声明:所有作者均声明不存在利益冲突。
作者贡献声明:邹怀宾负责查阅文献和撰写论文;任锋、陈煜负责修改论文;段钟平负责拟定写作思路,指导撰写文章并最后定稿。
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摘要: HDV需要借助HBV才能感染肝细胞并传播。HBV感染基础上合并HDV感染会加快病情进展且患者预后更差,但目前HDV感染的危害与疾病负担被严重低估。本文总结了HDV感染的流行病学、临床表现、诊断及治疗等方面研究进展,以期为更多的临床医生提供参考。Abstract: Hepatitis D virus (HDV) needs hepatitis B virus (HBV) as a helper to infect hepatocytes and spread. Co-infection with HDV and HBV may lead to accelerated progression and poor prognosis, but at present, the hazard and disease burden of HDV infection have been severely underestimated. This article summarizes the research advances in the epidemiology, clinical manifestations, diagnosis, and treatment of HDV infection, in order to provide a reference for more clinicians.
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Key words:
- Hepatitis D /
- Epidemiology /
- Diagnosis /
- Therapeutics
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[1] RIZZETTO M, CANESE MG, ARICÒ S, et al. Immunofluorescence detection of new antigen-antibody system (delta/anti-delta) associated to hepatitis B virus in liver and in serum of HBsAg carriers[J]. Gut, 1977, 18(12): 997-1003. DOI: 10.1136/gut.18.12.997. [2] BOTELHO-SOUZA LF, VASCONCELOS M, DOS SANTOS AO, et al. Hepatitis delta: Virological and clinical aspects[J]. Virol J, 2017, 14(1): 177. DOI: 10.1186/s12985-017-0845-y. [3] HUGHES SA, WEDEMEYER H, HARRISON PM. Hepatitis delta virus[J]. Lancet, 2011, 378(9785): 73-85. DOI: 10.1016/S0140-6736(10)61931-9. [4] URBAN S, NEUMANN-HAEFELIN C, LAMPERTICO P. Hepatitis D virus in 2021: Virology, immunology and new treatment approaches for a difficult-to-treat disease[J]. Gut, 2021, 70(9): 1782-1794. DOI: 10.1136/gutjnl-2020-323888. [5] BESOMBES C, NJOUOM R, PAIREAU J, et al. The epidemiology of hepatitis delta virus infection in Cameroon[J]. Gut, 2020, 69(7): 1294-1300. DOI: 10.1136/gutjnl-2019-320027. [6] TOY M, AHISHALI E, YURDAYD1N C. Hepatitis delta virus epidemiology in the industrialized world[J]. AIDS Rev, 2020, 22(4): 203-212. DOI: 10.24875/AIDSRev.20000056. [7] LEMPP FA, NI Y, URBAN S. Hepatitis delta virus: Insights into a peculiar pathogen and novel treatment options[J]. Nat Rev Gastroenterol Hepatol, 2016, 13(10): 580-589. DOI: 10.1038/nrgastro.2016.126. [8] STOCKDALE AJ, KREUELS B, HENRION M, et al. The global prevalence of hepatitis D virus infection: Systematic review and meta-analysis[J]. J Hepatol, 2020, 73(3): 523-532. DOI: 10.1016/j.jhep.2020.04.008. [9] ZHANG Z, URBAN S. New insights into HDV persistence: The role of interferon response and implications for upcoming novel therapies[J]. J Hepatol, 2021, 74(3): 686-699. DOI: 10.1016/j.jhep.2020.11.032. [10] CHEN HY, SHEN DT, JI DZ, et al. Prevalence and burden of hepatitis D virus infection in the global population: A systematic review and meta-analysis[J]. Gut, 2019, 68(3): 512-521. DOI: 10.1136/gutjnl-2018-316601. [11] MIAO Z, ZHANG S, OU X, et al. Estimating the global prevalence, disease progression, and clinical outcome of hepatitis delta virus infection[J]. J Infect Dis, 2020, 221(10): 1677-1687. DOI: 10.1093/infdis/jiz633. [12] SHEN DT, JI DZ, CHEN HY, et al. Hepatitis D: Not a rare disease anymore: Global update for 2017-2018[J]. Gut, 2020, 69(4): 786-788. DOI: 10.1136/gutjnl-2019-318691. [13] WU S, ZHANG Y, TANG Y, et al. Molecular epidemiology and clinical characteristics of hepatitis delta virus (HDV) infected patients with elevated transaminases in Shanghai, China[J]. BMC Infect Dis, 2020, 20(1): 565. DOI: 10.1186/s12879-020-05275-1. [14] ROULOT D, BRICHLER S, LAYESE R, et al. Origin, HDV genotype and persistent viremia determine outcome and treatment response in patients with chronic hepatitis delta[J]. J Hepatol, 2020, 73(5): 1046-1062. DOI: 10.1016/j.jhep.2020.06.038. [15] HERCUN J, KOH C, HELLER T. Hepatitis delta: Prevalence, natural history, and treatment options[J]. Gastroenterol Clin North Am, 2020, 49(2): 239-252. DOI: 10.1016/j.gtc.2020.01.004. [16] DIAS J, HENGST J, PARROT T, et al. Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells[J]. J Hepatol, 2019, 71(2): 301-312. DOI: 10.1016/j.jhep.2019.04.009. [17] THAM C, KAH J, TAN AT, et al. Hepatitis delta virus acts as an immunogenic adjuvant in hepatitis B virus-infected hepatocytes[J]. Cell Rep Med, 2020, 1(4): 100060. DOI: 10.1016/j.xcrm.2020.100060. [18] VIEIRA BARBOSA J, SAHLI R, AUBERT V, et al. Demographics and outcomes of hepatitis B and D: A 10-year retrospective analysis in a Swiss tertiary referral center[J]. PLoS One, 2021, 16(4): e0250347. DOI: 10.1371/journal.pone.0250347. [19] SAGNELLI C, SAGNELLI E, RUSSO A, et al. HBV/HDV co-infection: Epidemiological and clinical changes, recent knowledge and future challenges[J]. Life (Basel), 2021, 11(2): 169. DOI: 10.3390/life11020169. [20] BRICHLER S, LE GAL F, BUTT A, et al. Commercial real-time reverse transcriptase PCR assays can underestimate or fail to quantify hepatitis delta virus viremia[J]. Clin Gastroenterol Hepatol, 2013, 11(6): 734-740. DOI: 10.1016/j.cgh.2013.01.025. [21] LU XX, YI Y, SU QD, et al. Expression and purification of recombinant hepatitis delta virus (HDV) antigen for use in a diagnostic ELISA for HDV infection using the high-density fermentation strategy in Escherichia coli[J]. Biomed Environ Sci, 2016, 29(6): 417-423. DOI: 10.3967/bes2016.054. [22] CHEN X, OIDOVSAMBUU O, LIU P, et al. A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virus-infected mongolians[J]. Hepatology, 2017, 66(6): 1739-1749. DOI: 10.1002/hep.28957. [23] CHEN GH, ZHANG MD, HUANG W. Hepatitis delta virus superinfection in Guangzhou area[J]. Chin Med J (Engl), 1990, 103(6): 451-454. http://www.ncbi.nlm.nih.gov/pubmed/2119957 [24] JIANG YZ, ZHANG MC, TIAN RG, et al. Expression of the hepatitis Delta antigen in prokaryotic cell and evaluation of its application as an EIA diagnostic reagent[J]. Chin J Exp Clin Virol, 2006, 20(2): 38-41. DOI: 10.3760/cma.j.issn.1003-9279.2006.02.012.江永珍, 张明程, 田瑞光, 等. 丁型肝炎病毒抗原的原核表达及抗原性分析[J]. 中华实验和临床病毒学杂志, 2006, 20(2): 38-41. DOI: 10.3760/cma.j.issn.1003-9279.2006.02.012. [25] SHEN L, GU Y, SUN L, et al. Development of a hepatitis delta virus antibody assay for study of the prevalence of HDV among individuals infected with hepatitis B virus in China[J]. J Med Virol, 2012, 84(3): 445-449. DOI: 10.1002/jmv.23212. [26] GU WJ, HUANG WJ, ZHOU C, et al. Evaluate the HDV diagnostic kits (EIA) with HBV surface antigen positive sera[J]. Chin Pharm Affairs, 2011, 25(9): 866-868, 879. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201109009.htm辜文洁, 黄维金, 周诚, 等. 不同HDV诊断试剂对HBsAg阳性样品的检测分析[J]. 中国药事, 2011, 25(9): 866-868, 879. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYS201109009.htm [27] TAYLOR JM. Infection by hepatitis delta virus[J]. Viruses, 2020, 12(6): 648. DOI: 10.3390/v12060648. [28] LIN GY, WU YL, WANG CS, et al. Performance of commercially available anti-HDV enzyme-linked immunosorbent assays in Taiwan[J]. Virol J, 2020, 17(1): 76. DOI: 10.1186/s12985-020-01355-5. [29] STELZL E, CIESEK S, CORNBERG M, et al. Reliable quantification of plasma HDV RNA is of paramount importance for treatment monitoring: A European multicenter study[J]. J Clin Virol, 2021, 142: 104932. DOI: 10.1016/j.jcv.2021.104932. [30] KOH C, HELLER T, GLENN JS. Pathogenesis of and new therapies for hepatitis D[J]. Gastroenterology, 2019, 156(2): 461-476. DOI: 10.1053/j.gastro.2018.09.058. [31] BATTEGAY M, SIMPSON LH, HOOFNAGLE JH, et al. Elimination of hepatitis delta virus infection after loss of hepatitis B surface antigen in patients with chronic delta hepatitis[J]. J Med Virol, 1994, 44(4): 389-392. DOI: 10.1002/jmv.1890440413. [32] FARCI P, MANDAS A, COIANA A, et al. Treatment of chronic hepatitis D with interferon alfa-2a[J]. N Engl J Med, 1994, 330(2): 88-94. DOI: 10.1056/NEJM199401133300202. [33] CASTELNAU C, LE GAL F, RIPAULT MP, et al. Efficacy of peginterferon alpha-2b in chronic hepatitis delta: relevance of quantitative RT-PCR for follow-up[J]. Hepatology, 2006, 44(3): 728-735. DOI: 10.1002/hep.21325. [34] ABDRAKHMAN A, ASHIMKHANOVA A, ALMAWI WY. Effectiveness of pegylated interferon monotherapy in the treatment of chronic hepatitis D virus infection: A meta-analysis[J]. Antiviral Res, 2021, 185: 104995. DOI: 10.1016/j.antiviral.2020.104995. [35] SHELDON J, RAMOS B, TORO C, et al. Does treatment of hepatitis B virus (HBV) infection reduce hepatitis delta virus (HDV) replication in HIV-HBV-HDV-coinfected patients?[J]. Antivir Ther, 2008, 13(1): 97-102. http://med.wanfangdata.com.cn/DocDeliveryNstl/Index/PeriodicalPaper_JJ024367317 [36] YURDAYDIN C, BOZKAYA H, ONDER FO, et al. Treatment of chronic delta hepatitis with lamivudine vs lamivudine+interferon vs interferon[J]. J Viral Hepat, 2008, 15(4): 314-321. DOI: 10.1111/j.1365-2893.2007.00936.x. [37] KABAÇAM G, ONDER FO, YAKUT M, et al. Entecavir treatment of chronic hepatitis D[J]. Clin Infect Dis, 2012, 55(5): 645-650. DOI: 10.1093/cid/cis459. [38] WEDEMEYER H, YURDAYDÌN C, DALEKOS GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta[J]. N Engl J Med, 2011, 364(4): 322-331. DOI: 10.1056/NEJMoa0912696. [39] ABBAS Z, MEMON MS, UMER MA, et al. Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial[J]. World J Hepatol, 2016, 8(14): 625-631. DOI: 10.4254/wjh.v8.i14.625. [40] WEDEMEYER H, YURDAYDIN C, HARDTKE S, et al. Peginterferon alfa-2a plus tenofovir disoproxil fumarate for hepatitis D (HIDIT-Ⅱ): A randomised, placebo controlled, phase 2 trial[J]. Lancet Infect Dis, 2019, 19(3): 275-286. DOI: 10.1016/S1473-3099(18)30663-7. [41] BOGOMOLOV P, ALEXANDROV A, VORONKOVA N, et al. Treatment of chronic hepatitis D with the entry inhibitor myrcludex B: First results of a phase Ib/IIa study[J]. J Hepatol, 2016, 65(3): 490-498. DOI: 10.1016/j.jhep.2016.04.016. [42] LOGLIO A, FERENCI P, UCEDA RENTERIA SC, et al. Excellent safety and effectiveness of high-dose myrcludex-B monotherapy administered for 48 weeks in HDV-related compensated cirrhosis: A case report of 3 patients[J]. J Hepatol, 2019, 71(4): 834-839. DOI: 10.1016/j.jhep.2019.07.003. [43] WEDEMEYER H, SCHÖNEWEIS K, BOGOMOLOV P, et al. 48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV co-infection[J]. J Hepatol, 2020, 73(Suppl 1): s52-s53. http://www.sciencedirect.com/science/article/pii/S0168827820306516 [44] CHAN H, AHN SH, CHANG TT, et al. Peginterferon lambda for the treatment of HBeAg-positive chronic hepatitis B: A randomized phase 2b study (LIRA-B)[J]. J Hepatol, 2016, 64(5): 1011-1019. DOI: 10.1016/j.jhep.2015.12.018. [45] ETZION O, HAMID S, LURIE Y, et al. End of study results from LIMT HDV study: 36% durable virologic response at 24 weeks post-treatment with pegylated interferon lambda monotherapy in patients with chronic hepatitis delta virus infection[J]. J Hepatol, 2019, 70(Suppl 1): e32. [46] KOH C, HERCUN J, RAHMAN F, et al. A phase 2 study of peginterferon lambda, lonafarnib and ritonavir for 24 weeks: End-of-treatment results from the lift HDV study[J]. J Hepatol, 2020, 73: s130. http://www.sciencedirect.com/science/article/pii/S0168827820307741 [47] BALDRIDGE MT, LEE S, BROWN JJ, et al. Expression of Ifnlr1 on intestinal epithelial cells is critical to the antiviral effects of interferon lambda against norovirus and reovirus[J]. J Virol, 2017, 91(7): e02079-16. DOI: 10.1128/JVI.02079-16. [48] KOH C, CANINI L, DAHARI H, et al. Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: A proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial[J]. Lancet Infect Dis, 2015, 15(10): 1167-1174. DOI: 10.1016/S1473-3099(15)00074-2. [49] BERNDT N, HAMILTON AD, SEBTI SM. Targeting protein prenylation for cancer therapy[J]. Nat Rev Cancer, 2011, 11(11): 775-791. DOI: 10.1038/nrc3151. [50] YURDAYDIN C, KESKIN O, KALKAN Ç, et al. Optimizing lonafarnib treatment for the management of chronic delta hepatitis: The LOWR HDV-1 study[J]. Hepatology, 2018, 67(4): 1224-1236. DOI: 10.1002/hep.29658. [51] BEILSTEIN F, BLANCHET M, VAILLANT A, et al. Nucleic acid polymers are active against hepatitis delta virus infection in vitro[J]. J Virol, 2018, 92(4): e01416-17. DOI: 10.1128/JVI.01416-17. [52] VAILLANT A. REP 2139: Antiviral mechanisms and applications in achieving functional control of HBV and HDV infection[J]. ACS Infect Dis, 2019, 5(5): 675-687. DOI: 10.1021/acsinfecdis.8b00156.
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