UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

丁型肝炎病毒感染的治疗与预防

Authors
Francesco Negro, MD
Anna SF Lok, MD
Section Editor
Rafael Esteban, MD
Deputy Editor
Jennifer Mitty, MD, MPH
Translators
陈禄彪, 副主任医师

引言

丁型肝炎病毒(hepatitis D virus, HDV)感染的临床表现不一，可从良性急性肝炎到暴发性肝炎，从无症状携带状态到快速进展的慢性肝病。HDV是一种缺陷病毒，需要同时存在乙型肝炎病毒(hepatitis B virus, HBV)才能完全表达致病性；因此，丁型肝炎均发生在HBV感染的情况下。 (参见“Pathogenesis, epidemiology, natural history, and clinical manifestations of hepatitis D virus infection”)

大多数HDV感染病例中，由于受到HDV的抑制，HBV表现为低水平复制[1,2]。这类患者的肝脏损害基本上仅由HDV造成。HBV和HDV偶尔会同时复制，各自对肝脏造成损伤，从而导致更严重的肝病[3]。

HDV感染的临床病程

HDV感染的临床病程受多个因素的影响，包括HDV基因型[4]。这一问题将在别处详细讨论，但有必要在此进行简要总结，以阐明抗病毒治疗的理论依据。 (参见“Pathogenesis, epidemiology, natural history, and clinical manifestations of hepatitis D virus infection”)

在西方国家，HDV的主要基因型为Ⅰ型。慢性HDV感染一旦确立，其通常会加重既已存在的肝病(HBV感染所致)。患者向肝硬化进展的速度可能会很快，但并非所有患者都会发生。HDV相关的慢性肝病也可进展缓慢，已在某些地区发现了无症状的HDV携带者。

当前因HDV感染而转诊治疗的患者可能是一类在多年前已经感染的患者，在感染后他们的HDV相关疾病快速进展至肝硬化，但此后的进展速度又减慢。来自意大利的一项报道阐明了这一点。在该报道中，已经出现临床明显肝硬化的患者的估算5年和10年无肝移植生存概率分别为49%和40%[5]。已发现HBV和HDV复制都很活跃的患者更容易进展为肝功能失代偿[5]。在远东地区，HDV的主要基因型为Ⅱ型，慢性HDV感染导致进行性肝病的情况较少[4]。

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: 2017-06 . | This topic last updated: 2016-04-29.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
References
Top
  1. Krogsgaard K, Kryger P, Aldershvile J, et al. Delta-infection and suppression of hepatitis B virus replication in chronic HBsAg carriers. Hepatology 1987; 7:42.
  2. Farci P, Karayiannis P, Lai ME, et al. Acute and chronic hepatitis delta virus infection: direct or indirect effect on hepatitis B virus replication? J Med Virol 1988; 26:279.
  3. Smedile A, Rosina F, Saracco G, et al. Hepatitis B virus replication modulates pathogenesis of hepatitis D virus in chronic hepatitis D. Hepatology 1991; 13:413.
  4. Wu JC, Choo KB, Chen CM, et al. Genotyping of hepatitis D virus by restriction-fragment length polymorphism and relation to outcome of hepatitis D. Lancet 1995; 346:939.
  5. Rosina F, Conoscitore P, Cuppone R, et al. Changing pattern of chronic hepatitis D in Southern Europe. Gastroenterology 1999; 117:161.
  6. Negro F, Shapiro M, Satterfield WC, et al. Reappearance of hepatitis D virus (HDV) replication in chronic hepatitis B virus carrier chimpanzees rechallenged with HDV. J Infect Dis 1989; 160:567.
  7. Abbas Z, Khan MA, Salih M, Jafri W. Interferon alpha for chronic hepatitis D. Cochrane Database Syst Rev 2011; :CD006002.
  8. Ilan Y, Klein A, Taylor J, Tur-Kaspa R. Resistance of hepatitis delta virus replication to interferon-alpha treatment in transfected human cells. J Infect Dis 1992; 166:1164.
  9. McNair AN, Cheng D, Monjardino J, et al. Hepatitis delta virus replication in vitro is not affected by interferon-alpha or -gamma despite intact cellular responses to interferon and dsRNA. J Gen Virol 1994; 75 ( Pt 6):1371.
  10. Pugnale P, Pazienza V, Guilloux K, Negro F. Hepatitis delta virus inhibits alpha interferon signaling. Hepatology 2009; 49:398.
  11. Lau JY, King R, Tibbs CJ, et al. Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection. J Med Virol 1993; 39:292.
  12. 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 Med Virol 1994; 44:389.
  13. Lau DT, Kleiner DE, Park Y, et al. Resolution of chronic delta hepatitis after 12 years of interferon alfa therapy. Gastroenterology 1999; 117:1229.
  14. Rosina F, Pintus C, Meschievitz C, Rizzetto M. A randomized controlled trial of a 12-month course of recombinant human interferon-alpha in chronic delta (type D) hepatitis: a multicenter Italian study. Hepatology 1991; 13:1052.
  15. Farci P, Mandas A, Coiana A, et al. Treatment of chronic hepatitis D with interferon alfa-2a. N Engl J Med 1994; 330:88.
  16. Farci P, Roskams T, Chessa L, et al. Long-term benefit of interferon alpha therapy of chronic hepatitis D: regression of advanced hepatic fibrosis. Gastroenterology 2004; 126:1740.
  17. Borghesio E, Rosina F, Di Marco V, et al. Long-term treatment of chronic hepatitis D with lymphoblastoid interferon: 10 MU vs. 5 MU. An interim report of a randomized controlled trial. Proceedings of the Fifth International Symposium on Hepatitis Delta Virus and Liver Disease. Brisbane, August 28-29, 1995; D47.
  18. Gaudin JL, Faure P, Godinot H, et al. The French experience of treatment of chronic type D hepatitis with a 12-month course of interferon alpha-2B. Results of a randomized controlled trial. Liver 1995; 15:45.
  19. Niro GA, Ciancio A, Gaeta GB, et al. Pegylated interferon alpha-2b as monotherapy or in combination with ribavirin in chronic hepatitis delta. Hepatology 2006; 44:713.
  20. 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. Hepatology 2006; 44:728.
  21. Ferenci P, Formann E, Romeo R. Successful treatment of chronic hepatitis D with a short course of peginterferon alfa-2a. Am J Gastroenterol 2005; 100:1626.
  22. Ormeci N, Bölükbaş F, Erden E, et al. Pegylated interferon alfa-2B for chronic delta hepatitis: 12 versus 24 months. Hepatogastroenterology 2011; 58:1648.
  23. Abbas Z, Memon MS, Mithani H, et al. Treatment of chronic hepatitis D patients with pegylated interferon: a real-world experience. Antivir Ther 2014; 19:463.
  24. Ouzan D, Pénaranda G, Joly H, Halfon P. Optimized HBsAg titer monitoring improves interferon therapy in patients with chronic hepatitis delta. J Hepatol 2013; 58:1258.
  25. Wedemeyer H, Yurdaydìn C, Dalekos GN, et al. Peginterferon plus adefovir versus either drug alone for hepatitis delta. N Engl J Med 2011; 364:322.
  26. Rasshofer R, Choi SS, Wolfl P, et al. Inhibition of HDV RNA replication in vitro by ribavirin and suramin. In: Viral Hepatitis and Liver Disease, Hollinger FB, Lemon SM, Margolis HS (Eds), Williams & Wilkins, Baltimore 1991. p.659.
  27. Buti M, Lopez-Talavera JC, Allende H, et al. Serological diagnosis of chronic delta infection: correlation between serological markers and hepatitis delta virus RNA in hepatic tissue. Prog Clin Biol Res 1993; 382:319.
  28. Garripoli A, Di Marco V, Cozzolongo R, et al. Ribavirin treatment for chronic hepatitis D: a pilot study. Liver 1994; 14:154.
  29. Petcu DJ, Aldrich CE, Coates L, et al. Suramin inhibits in vitro infection by duck hepatitis B virus, Rous sarcoma virus, and hepatitis delta virus. Virology 1988; 167:385.
  30. Ponzetto A, Negro F, Gerin JL, Purcell RH. Experimental hepatitis delta virus infection in the animal model. Prog Clin Biol Res 1991; 364:147.
  31. Lau DT, Doo E, Park Y, et al. Lamivudine for chronic delta hepatitis. Hepatology 1999; 30:546.
  32. Niro GA, Ciancio A, Tillman HL, et al. Lamivudine therapy in chronic delta hepatitis: a multicentre randomized-controlled pilot study. Aliment Pharmacol Ther 2005; 22:227.
  33. Wolters LM, van Nunen AB, Honkoop P, et al. Lamivudine-high dose interferon combination therapy for chronic hepatitis B patients co-infected with the hepatitis D virus. J Viral Hepat 2000; 7:428.
  34. Yurdaydin C, Bozkaya H, Onder FO, et al. Treatment of chronic delta hepatitis with lamivudine vs lamivudine + interferon vs interferon. J Viral Hepat 2008; 15:314.
  35. Yurdaydin C, Bozkaya H, Gürel S, et al. Famciclovir treatment of chronic delta hepatitis. J Hepatol 2002; 37:266.
  36. Zhang FL, Casey PJ. Protein prenylation: molecular mechanisms and functional consequences. Annu Rev Biochem 1996; 65:241.
  37. Bordier BB, Marion PL, Ohashi K, et al. A prenylation inhibitor prevents production of infectious hepatitis delta virus particles. J Virol 2002; 76:10465.
  38. Bordier BB, Ohkanda J, Liu P, et al. In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus. J Clin Invest 2003; 112:407.
  39. Koh C, Yurdaydin C, Cooper S, et al. Prenylation inhibition with lonafarnib decreases hepatitis D levels in humans. Hepatology 2014;60(suppl):1092A
  40. Ni Y, Lempp FA, Mehrle S, et al. Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes. Gastroenterology 2014; 146:1070.
  41. Yan H, Zhong G, Xu G, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 2012; 1:e00049.
  42. Urban S, Bogomolov P, Voronkova N, et al. A proof-of-concept Phase 2a clinical trial with HBV/HDV entry inhibitor Myrcludex B. Hepatology 2014;60(suppl):LB-20
  43. Chen TZ, Wu JC, Au LC, Choo KB. Specific inhibition of delta antigen by in vitro system by antisense oligodeoxynucleotide: implications for translation mechanism and treatment. J Virol Methods 1997; 65:183.
  44. Hedin G, Weiland O, Ljunggren K, et al. Treatment of fulminant hepatitis B and fulminant hepatitis B and D coinfection with foscarnet. Prog Clin Biol Res 1987; 234:309.
  45. Rizzetto M, Canese MG, Gerin JL, et al. Transmission of the hepatitis B virus-associated delta antigen to chimpanzees. J Infect Dis 1980; 141:590.
  46. Ponzetto A, Forzani B, D'Urso N, et al. Immunization with hepatitis delta antigen does not prevent superinfection with hepatitis delta virus in the woodchuck. Gastroenterology 1989; 96:646.
  47. Karayiannis P, Saldanha J, Monjardino J, et al. Immunization of woodchucks with recombinant hepatitis delta antigen does not protect against hepatitis delta virus infection. Hepatology 1990; 12:1125.
  48. Ponzetto A, Eckart M, D'Urso N, et al. Towards a vaccine for the prevention of hepatitis delta virus superinfection in HBV carriers. Prog Clin Biol Res 1993; 382:207.
  49. Karayiannis P, Saldanha J, Jackson AM, et al. Partial control of hepatitis delta virus superinfection by immunisation of woodchucks (Marmota monax) with hepatitis delta antigen expressed by a recombinant vaccinia or baculovirus. J Med Virol 1993; 41:210.
  50. Eckart MR, Dong C, Houghton M, et al. The effects of using recombinant vaccinia viruses expressing either large or small HDAg to protect woodchuck hepadnavirus carriers from HDV superinfection. Prog Clin Biol Res 1993; 382:201.
  51. Bergmann KF, Casey JL, Tennant BC, Gerin JL. Modulation of hepatitis delta virus infection by vaccination with synthetic peptides: a preliminary study in the woodchuck model. Prog Clin Biol Res 1993; 382:181.