重视丁型肝炎研究

庄辉

doi:10.3969/j.issn.1001-5256.2023.04.001

重视丁型肝炎研究

DOI: 10.3969/j.issn.1001-5256.2023.04.001

庄辉^, ,

北京大学医学部基础医学院病原生物学系暨感染病中心，北京 100191

利益冲突声明：作者声明不存在利益冲突。

详细信息

通信作者:
庄辉，zhuanghuibmu@163.com (ORCID: 0000-0001-9119-6325)

计量
- 文章访问数: 447
- HTML全文浏览量: 77
- PDF下载量: 123
- 被引次数: 0
出版历程
- 收稿日期: 2023-02-01
- 录用日期: 2023-03-06
- 出版日期: 2023-04-20

The research on hepatitis D should be taken seriously

Hui ZHUANG^{,
,}

Department of Microbiology and Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

More Information

Corresponding author: ZHUANG Hui, zhuanghuibmu@163.com (ORCID: 0000-0001-9119-6325)

摘要

摘要: 丁型肝炎病毒感染是全球重要的公共卫生问题。10余年来，由于广泛的乙型肝炎疫苗免疫和移民，丁型肝炎病毒感染的流行病学发生了显著改变。丁型肝炎病毒感染可表现为联合感染或重叠感染。乙型肝炎病毒与丁型肝炎病毒合并感染的患者发生肝硬化和肝细胞癌的风险远高于乙型肝炎病毒单独感染者。新的治疗丁型肝炎药物已在研发中，部分已进入Ⅲ期临床试验，未来有望取代疗效较低的现行药物。
- 丁型肝炎 /
- 病毒学 /
- 流行病学 /
- 体征和症状 /
- 药物疗法
Abstract: Hepatitis D virus (HDV) infection is an important health problem around the world. The epidemiology of HDV infection has been changed significantly over the past 10 years due to widespread hepatitis B vaccination and human migration. HDV infection can manifest as co-infection or superinfection. Patients with HBV/HDV co-infection have a significantly higher risk of liver cirrhosis and hepatocellular carcinoma than those with HBV infection alone. Research and development are being conducted for new therapeutic drugs for hepatitis D, some of which have entered phase Ⅲ clinical trials. These drugs will replace the current therapies with lower efficacy.
- Hepatitis D /
- Virology /
- Epidemiology /
- Signs and Symptoms /
- Drug Therapy

HTML全文

参考文献(51)

[1]	BENDER D, GLITSCHER M, HILDT E. Viral hepatitis A to E: prevalence, pathogen characteristics, and pathogenesis[J]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz, 2022, 65(2): 139-148. DOI: 10.1007/s00103-021-03472-0.
[2]	FLORES R, RUIZ-RUIZ S, SERRA P. Viroids and hepatitis delta virus[J]. Semin Liver Dis, 2012, 32(3): 201-210. DOI: 10.1055/s-0032-1323624.
[3]	PÉREZ-VARGAS J, PEREIRA DE OLIVEIRA R, JACQUET S, et al. HDV-like viruses[J]. Viruses, 2021, 13(7): 1207. DOI: 10.3390/v13071207.
[4]	DANDRI M, LVTGEHETMANN M. Mouse models of hepatitis B and delta virus infection[J]. J Immunol Methods, 2014, 410: 39-49. DOI: 10.1016/j.jim.2014.03.002.
[5]	GIERSCH K, HELBIG M, VOLZ T, et al. Persistent hepatitis D virus mono-infection in humanized mice is efficiently converted by hepatitis B virus to a productive co-infection[J]. J Hepatol, 2014, 60(3): 538-544. DOI: 10.1016/j.jhep.2013.11.010.
[6]	OTTOBRELLI A, MARZANO A, SMEDILE A, et al. Patterns of hepatitis delta virus reinfection and disease in liver transplantation[J]. Gastroenterology, 1991, 101(6): 1649-1655. DOI: 10.1016/0016-5085(91)90404-9.
[7]	MEDERACKE I, FILMANN N, YURDAYDIN C, et al. Rapid early HDV RNA decline in the peripheral blood but prolonged intrahepatic hepatitis delta antigen persistence after liver transplantation[J]. J Hepatol, 2012, 56(1): 115-122. DOI: 10.1016/j.jhep.2011.06.016.
[8]	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.
[9]	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.
[10]	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.
[11]	RIZZETTO M, HAMID S, NEGRO F. The changing context of hepatitis D[J]. J Hepatol, 2021, 74(5): 1200-1211. DOI: 10.1016/j.jhep.2021.01.014.
[12]	RIZZETTO M. Hepatitis D (DELTA)[J]. New Microbiol, 2022, 45(3): 149-154.
[13]	ROBINSON A, WONG R, GISH RG. Chronic hepatitis B virus and hepatitis D virus: New developments[J]. Clin Liver Dis, 2023, 27(1): 17-25. DOI: 10.1016/j.cld.2022.08.001.
[14]	BLANEY H, KHALID M, HELLER T, et al. Epidemiology, presentation, and therapeutic approaches for hepatitis D infections[J]. Expert Rev Anti Infect Ther, 2023, 21(2): 127-142. DOI: 10.1080/14787210.2023.2159379.
[15]	ROGGENBACH I, CHI X, LEMPP FA, et al. HDV seroprevalence in HBsAg-positive patients in China occurs in hotspots and is not associated with HCV mono-infection[J]. Viruses, 2021, 13(9): 1799. DOI: 10.3390/v13091799.
[16]	WANG Y. Survey of HDV infection and molecular characterization of HDV, HBV and HIV-1 among chronic hepatitis B patients in China[D]. Beijing: Chinese Center for Disease Control and Prevention, 2018. 王彦. 我国丁型肝炎病毒感染情况调查和病毒分子特性研究[D]. 北京: 中国疾病预防控制中心, 2018.
[17]	LIU YM, GUO XP, ZHANG HM, et al. An investigation of hepatitis D virus infection among patients with chronic hepatitis B virus infection in some regions of China[J]. J Clin Hepatol, 2023, 39(4): 795-803. DOI: 10.3969/j.issn.1001-5256.2023.04.009. 刘玉梅, 郭小平, 张慧敏, 等. 我国部分地区慢性HBV感染者HDV感染情况调查[J]. 临床肝胆病杂志, 2023, 39(4): 795-803. DOI: 10.3969/j.issn.1001-5256.2023.04.009.
[18]	WRANKE A, PINHEIRO BORZACOV LM, PARANA R, et al. Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN)[J]. Liver Int, 2018, 38(5): 842-850. DOI: 10.1111/liv.13604.
[19]	NIRO GA, FERRO A, CICERCHIA F, et al. Hepatitis delta virus: From infection to new therapeutic strategies[J]. World J Gastroenterol, 2021, 27(24): 3530-3542. DOI: 10.3748/wjg.v27.i24.3530.
[20]	FATTOVICH G, GIUSTINA G, CHRISTENSEN E, et al. Influence of hepatitis delta virus infection on morbidity and mortality in compensated cirrhosis type B. The European Concerted Action on Viral Hepatitis (Eurohep)[J]. Gut, 2000, 46(3): 420-426. DOI: 10.1136/gut.46.3.420.
[21]	ALFAIATE D, CLÉMENT S, GOMES D, et al. Chronic hepatitis D and hepatocellular carcinoma: A systematic review and meta-analysis of observational studies[J]. J Hepatol, 2020, 73(3): 533-539. DOI: 10.1016/j.jhep.2020.02.030.
[22]	FARCI P, NIRO GA, ZAMBONI F, et al. Hepatitis D virus and hepatocellular carcinoma[J]. Viruses, 2021, 13(5): 830. DOI: 10.3390/v13050830.
[23]	SHEN C, JIANG X, LI M, et al. Hepatitis virus and hepatocellular carcinoma: Recent advances[J]. Cancers (Basel), 2023, 15(2): 533. DOI: 10.3390/cancers15020533.
[24]	STROFFOLINI T, MORISCO F, FERRIGNO L, et al. Acute Delta Hepatitis in Italy spanning three decades (1991-2019): Evidence for the effectiveness of the hepatitis B vaccination campaign[J]. J Viral Hepat, 2022, 29(1): 78-86. DOI: 10.1111/jvh.13620.
[25]	PONZETTO A, HOYER BH, POPPER H, et al. Titration of the infectivity of hepatitis D virus in chimpanzees[J]. J Infect Dis, 1987, 155(1): 72-78. DOI: 10.1093/infdis/155.1.72.
[26]	TERRAULT NA, GHANY MG. Enhanced screening for hepatitis D in the USA: overcoming the delta blues[J]. Dig Dis Sci, 2021, 66(8): 2483-2485. DOI: 10.1007/s10620-020-06584-w.
[27]	LIU J, LIANG W, JING W, et al. Countdown to 2030: eliminating hepatitis B disease, China[J]. Bull World Health Organ, 2019, 97(3): 230-238. DOI: 10.2471/BLT.18.219469.
[28]	LIU HM, TAN ZX, YANG J, et al. Prevalence and clinical characteristics of hepatitis D in Southwest of China[J]. Chin J Exp Clin Virol, 2022, 36(1): 85-91. DOI: 10.3760/cma.j.cn112866-20210611-00096. 刘慧敏, 谭朝霞, 杨京, 等. 中国西南地区丁型肝炎的流行状况与临床特征分析[J]. 中华实验和临床病毒学杂志, 2022, 36(1): 85-91. DOI: 10.3760/cma.j.cn112866-20210611-00096.
[29]	SARACCO GM, MARZANO A, RIZZETTO M. Therapy of chronic viral hepatitis: The light at the end of the tunnel?[J]. Biomedicines, 2022, 10(3): 534. DOI: 10.3390/biomedicines10030534.
[30]	RIZZETTO M. Targeting hepatitis D[J]. Semin Liver Dis, 2018, 38(1): 66-72. DOI: 10.1055/s-0037-1621711.
[31]	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.
[32]	BREMER B, ANASTASIOU OE, HARDTKE S, et al. Residual low HDV viraemia is associated HDV RNA relapse after PEG-IFNa-based antiviral treatment of hepatitis delta: Results from the HIDIT-Ⅱ study[J]. Liver Int, 2021, 41(2): 295-299. DOI: 10.1111/liv.14740.
[33]	European Medicines Agency. Hepcludex: EU assessment report[R/OL]. (2022-08-31)[2023-02-01]. https://www.ema.europa.eu.
[34]	WEDEMEYER H, SCHONEWEIS K, BOGOMOLOV PO, et al. Final results of a multicenter, open-label phase 2 clinical trial (MYR203) to assess safety and efcacy of Myrcludex B in with PEG-interferon alpha 2a in patients with chronic HBV/HDV co-infection[abstract no. GS-13][J]. J Hepatol, 2019, 70(1): e81.
[35]	WEDEMEYER H, SCHONEWEIS K, BOGOMOLOV P, et al. Safety and efcacy of 10 mg (high-dose) bulevirtide (Myrcludex B) in combination with PEG-interferon alpha 2a or tenofovir in patients with chronic HBV/HDV co-infection: week 24 interim results of the MYR203 extension study[abstract no. 85][J]. Hepatology, 2019, 70(Suppl 1): 58A-59A.
[36]	European Medicines Agency. Hepcludex[EB/OL]. (2021-04-15)[2023-02-01]. https://www.ema.europa.eu/en/medicines/human/EPAR/hepcludex.
[37]	KANG C, SYED YY. Bulevirtide: First approval[J]. Drugs, 2020, 80(15): 1601-1605. DOI: 10.1007/s40265-020-01400-1.
[38]	BORDIER BB, MARION PL, OHASHI K, et al. A prenylation inhibitor prevents production of infectious hepatitis delta virus particles[J]. J Virol, 2002, 76(20): 10465-10472. DOI: 10.1128/jvi.76.20.10465-10472.2002.
[39]	KOH C, SURANA P, HAN T, et al. A phase 2 study exploring once daily dosing of ritonavir boosted lonafarnib for the treatment of chronic delta hepatitis - end of study results from the LOWR HDV-3 study[J]. J Hepatol, 2017, 66 (1): S101-S102.
[40]	WEDEMEYER H, PORT K, DETERDING K, et al. A phase 2 dose-escalation study of lonafarnib plus ritonavir in patients with chronic hepatitis D: final results from the lonafarnib with ritonavir in HDV-4 (LOWR HDV-4) study[J]. J Hepatol, 2017, 66 (1): S24.
[41]	YARDENI D, HELLER T, KOH C. Chronic hepatitis D-What is changing?[J]. J Viral Hepat, 2022, 29(4): 240-251. DOI: 10.1111/jvh.13651.
[42]	VAILLANT A. Nucleic acid polymers: Broad spectrum antiviral activity, antiviral mechanisms and optimization for the treatment of hepatitis B and hepatitis D infection[J]. Antiviral Res, 2016, 133: 32-40. DOI: 10.1016/j.antiviral.2016.07.004.
[43]	BOULON R, BLANCHET M, LEMASSON M, et al. Characterization of the antiviral effects of REP 2139 on the HBV lifecycle in vitro[J]. Antiviral Res, 2020, 183: 104853. DOI: 10.1016/j.antiviral.2020.104853.
[44]	BAZINET M, PÂNTEA V, CEBOTARESCU V, et al. Safety and efficacy of REP 2139 and pegylated interferon alfa-2a for treatment-naive patients with chronic hepatitis B virus and hepatitis D virus co-infection (REP 301 and REP 301-LTF): a non-randomised, open-label, phase 2 trial[J]. Lancet Gastroenterol Hepatol, 2017, 2(12): 877-889. DOI: 10.1016/S2468-1253(17)30288-1.
[45]	BAZINET M, PÂNTEA V, CEBOTARESCU V, et al. Persistent control of hepatitis B virus and hepatitis delta virus infection following REP 2139-Ca and pegylated interferon therapy in chronic hepatitis B virus/hepatitis delta virus coinfection[J]. Hepatol Commun, 2021, 5(2): 189-202. DOI: 10.1002/hep4.1633.
[46]	LASFAR A, ABUSHAHBA W, BALAN M, et al. Interferon lambda: a new sword in cancer immunotherapy[J]. Clin Dev Immunol, 2011, 2011: 349575. DOI: 10.1155/2011/349575.
[47]	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 (Suppl 1): S130.
[48]	DHILLON S. Lonafarnib: First approval[J]. Drugs, 2021, 81(2): 283-289. DOI: 10.1007/s40265-020-01464-z.
[49]	DA BL. Clinical trials in hepatitis D virus: Measuring success[J]. Hepatology, 2022. DOI: 10.1002/hep.32732.[Online ahead of print]
[50]	Eiger BioPharmaceuticals. Phase 3 study to evaluate the efficacy and safety of peginterferon lambda for 48weeks in patients with chronic HDV (LIMT-2). ClinicalTrials. gov identifier: NCT05070364[DB/OL]. (2022-07-22)[2022-08-03]. https://clinicaltrials.gov/ct2/show/NCT05070364.
[51]	Food and Drug Administration (FDA). Chronic hepatitis D virus infection: Developing drugs for treatment guidance for industry[EB/OL]. (2019-10-31)[2023-02-01]. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/chronic-hepatitis-d-virus-infection-developing-drugs-treatment-guidance-industry.