YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Drugs for the Treatment of Viral Hepatitis

바이러스성 간질환 치료약

  • Kim, Choong Sup (ReSeat Program, Korea Institute of Science and Technology Information)
  • 김충섭 (한국과학기술 정보연구원)
  • Received : 2012.11.06
  • Accepted : 2013.02.25
  • Published : 2013.02.28
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Abstract

Viral hepatitis is the inflammation of liver cells caused by viruses, and still one of the major health-care problems worldwide. A number of viruses to cause hepatitis are type A, B, C, D, E or G. Among these viruses leading to hepatitis, B and C are more troublesome being more prone to chronic illness which can cause the potentially fatal conditions of hepatocellular carcinoma (HCC) and/or liver failure. If immediate treatment is not initiated, liver transplant is the only option left. Over the past few decades there has been remarkable progress in diagnose and monitor all hepatitis virus infections for treatment and prevention. Nonetheless, important challenges remain to develop more effective and safe vaccines for prevention as well as antiviral agents to reduce viremia/viral load by inhibiting viral replication. The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years has heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus. The introduction of Direct Acting Antivirals (DDAs) for the treatment of HBV carriers has permitted the long term use of these compounds for the continuous suppression of viral replication. This review aims to summarize the current status and development approaches of antiviral drugs for the treatment of viral hepatitis and future perspectives.

Keywords

References

  1. HB El-Serag : Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 142, 1264 (2012). https://doi.org/10.1053/j.gastro.2011.12.061
  2. Karayiannis, P. : Direct Acting Antivirals for the treatment of chronic viral hepatitis. Scientifica Review 1 (2012).
  3. European Pharmacopoeia 5.0, (2005), Hepatitis A Vaccine (inactivated, adsorbed).
  4. Pevion Biotech Ltd., Website: www.pevion.com/images/content/pevion_virosomesheet_vaccines_Oct4.pdf, :Virosomal Vaccine Plaftforms. Oct. 2012.
  5. Christian Moser, Ian C Metcalfe and Jean-Franois Viret : Virosomal adjuvant antigen delivery systems. Expert Reviews Vaccine 2, 189 (2003). https://doi.org/10.1586/14760584.2.2.189
  6. Valrie D'Acremont, Christian Herzog and Blaise Genton : Immunogenicity and safety of a virosomal hepatitis A vaccine ($Epaxal^{(R)}$) in the elderly. J. of Travel Medicine 13, 78 (2006). https://doi.org/10.1111/j.1708-8305.2006.00001.x
  7. Steven G. Reed, Sylvie Bertholet, Rhea N. Coler and Martin Friede : New horizons in adjuvants for vaccine development. Trends in Immunology 30, 23 (2009). https://doi.org/10.1016/j.it.2008.09.006
  8. GamaSTAN Website http://www.talecris-pi.info/inserts/gamastans-d.pdf, "Immune globulin (Human)", April. 2012.
  9. 박상훈 : A형간염 : 과거와 현재. J. Kor. Med. Assoc. 52, 996 (2009). https://doi.org/10.5124/jkma.2009.52.10.996
  10. 정숙향 : A형 간염백신. Hanyang Medical Rewiew 28, 16 (2008).
  11. 이응준 : 최근 2년간 발생한 급성 A형간염의 임상특성에 관한 연구. 대한소화기학회지 52, 298 (2008).
  12. Moon, H. W., Cho, J. H., Hur, M., Yun, Y.-M., Choe, W. H., Kwon, S. Y. and Lee, C. H. : Laboratory characteristics of recent hepatitis A in Korea : Ongoing epidemiological shift. World J. Gastroenterol. 16, 1115 (2010). https://doi.org/10.3748/wjg.v16.i9.1115
  13. Lee, H., Cho, H. K., Kim, J. H. and Kim, K. H. : Seroepidemiology of Hepatitis A in Korea : Changes over the Past 30 Years. J. Korean Med. Sci. 26, 791 (2011). https://doi.org/10.3346/jkms.2011.26.6.791
  14. Barakat, A. B., Shoman, A. S., Dina, N. and Alfarouk, O. R. : Antiviral activity and mode of action of Dianthus caryophyllus L. and Lupinus termes L. seed extracts against in vitro herpes simplex and hepatitis A viruses infection. J. Microb. & Antimicrobials 2, 23 (2010).
  15. Dandri, M. and Locarnini, S. : New insight in the pathobiology of hepatitis B virus infection. Gut 61, i6 (2012). https://doi.org/10.1136/gutjnl-2012-302056
  16. D. Shouval, Hepatitis B vaccines. Journal of Hepatology 39, S70 (2003). https://doi.org/10.1016/S0168-8278(03)00152-1
  17. Dynavax Website, http://www.dynavax.com/hepatitis_bv.html.
  18. Marcellin, P., Chang, T. T., Lim, S. G., Tong, M. J., Sievert, W., Shiffman, M. L., Jeffers, L., Goodman, Z., Wulfsohn, M. S., Xiong, S., Fry, J. and Brosgart, C. L. : Adefovir Dipivoxil 437 Study Group. : Adefovir dipivoxil for the treatment of hepatitis Be antigen-positive chronic hepatitis B. N. Engl. J. Med. 348, 8081 (2003).
  19. Sims, K. A. and Woodland, A. M. : Entecavir a new nucleoside analog for the treatment of chronic hepatitis B infection. Pharmacotherapy 269, 1745 (2006).
  20. Lai, C. L., Gane, E., Liaw, Y. F. and Hsu, C. W. : Pharmacokinetics and dosing recommendation of tenofovir disoproxil fumarate in hepatic or renal impairment. Clin. Pharmacokinet. 45, 11151 (2006).
  21. Lai, C. L., Gane, E., Liaw, Y. F. and Hsu, C. W. : Telbivudine versus lamivudine in patients with chronic hepatitis B. N. Eng. J. Med. 257, 2576 (2007).
  22. Yuen, M. F. and Lai, C. L. : Current and future antiviral agents for chronic hepatitis B. J. Antimicrobial Chemotherapy 51, 481 (2003). https://doi.org/10.1093/jac/dkg122
  23. Lee, K., Chang, S. and Su, Y. : Clinical and virologic outcomes after switch to tenoforvir/lamibudine of HIV infected patients with hepatitis B virus (HBV) resitance to lamibudine in an hyperendemic area for HBV infection, 52nd Intersci. Conference on Antimicrobial Agents and Chemotherapy, San Francisco, Abstract H-218 (2012).
  24. Perrillo, R. P. and Marcellin, P. : Effect of newer oral antiviral agents on future therapy of chronic hepetitis B. Antiviral Therapy 15, 13 (2010). https://doi.org/10.3851/IMP1482
  25. Woo, G., Tomlinson, G., Nishikawa, Y., Kowgier, M., Sherman, M., Wong, D. K., Pham, B., Ungar, W. J., Einarson, T. R., Heathcote, E. J. and Krahn, M. : Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: A systematic review and bayesian meta-analyses. Gastroenterology 139, 1218 (2010). https://doi.org/10.1053/j.gastro.2010.06.042
  26. Lee, H. S., Chung, Y. H., Lee, K., Byun, K. S., Paik, S. W., Han, J. Y., Yoo, K., Yoo, H. W., Lee, J. H. and Yoo, B. C. : A 12-week clevudine therapy showed potent and durable antiviral activity in HBeAg- positive chronic hepatitis B. Hepatology 43, 982 (2006). https://doi.org/10.1002/hep.21166
  27. Lau, G. K. and Leung, N. : Forty-eight weeks treatment with clevudine 30 mg qd versus lamivudine 100 mg qd for chronic hepatitis B infection: a double-blind randomized study. Korean J. Hepatol. 16, 315 (2010). https://doi.org/10.3350/kjhep.2010.16.3.315
  28. Yuen, M. F., Han, K. H., Um, S. H., Yoon, S. K., Kim, H. R., Kim, J., Kim, C. R. and Lai, C. L. : Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease. Hepatology 51, 767 (2010). https://doi.org/10.1002/hep.23462
  29. Brunelle, M. N., Lucifora, J., Neyts, J., Holy, V. A., Trepo, C. and Zoulim, F. : In vitro activity of 2,4-diamino-6-[2-(phosphomethoxy) ethoxy]pyrimidine against multidrug resistant hepatitis B virus mutants. Antimicrob Agents Chemotherapy 51, 2240 (2007). https://doi.org/10.1128/AAC.01440-06
  30. Balzarini, J., Pannecouque, C., Naesens, L., Andrei, G., Snoeck, R., Clercq, E. D. and Hockova, D. : A 6-[2-phosphonomethoxy) alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity. Nucleotides Nucleic Acids 23, 1321 (2004). https://doi.org/10.1081/NCN-200027573
  31. Kim, S. H. : HBV neutralizing human monoclonal antibody (GC1102) for liver transplantation & chronic hepatitis B treatment. 한국생물공학회 학술대회 초록, p. 91 (2010).
  32. Grimm, D., Thimme, R. and Blum, H. E. : HBV life cycle and novel drug target. Hepatol. Int. 5, 644 (2011). https://doi.org/10.1007/s12072-011-9261-3
  33. Ryu, D.-K., Ahn, B.-Y. and Ryu, W.-S. : Proximity between the cap and 5' ${\varepsilon}$ stemploop structure is critical for the suppression of pgRNA translation by the hepatitis B viral polymerase.Virology 406, 56 (2010). https://doi.org/10.1016/j.virol.2010.07.005
  34. Chou, L. : Hepatitis B Drugs i9n Development. TAG 2010 Pipe Line Report, pp. 70-76 (2010).
  35. Seto, W. K., Fung, J., Yuen, M. F. and Lai, C. L. : Future prevention and treatment of chronic hepatitis B infection. J. Clin. Gastroenterol. 46, 725 (2012). https://doi.org/10.1097/MCG.0b013e3182610191
  36. Hofmann, W. P. and Zeuzem, S. A. : New standard of care for the treatment of chronic HCV infection. Nature Reviews Gastroenterology & Hepatology 8, 257 (2011). https://doi.org/10.1038/nrgastro.2011.49
  37. Jason Grebely, Gail V. Matthews and Gregory J. Dore : Treatment of acute HCV infection. Nat. Rev. Gastroenterol. and Hepatol. 8, 265 (2011). https://doi.org/10.1038/nrgastro.2011.32
  38. Asselah, T. and Marcellin, P. : Direct acting antivirals for the treatment of chronic hepatitis C: one pill a day for tomorrow. Liver International 32, 88 (2012). https://doi.org/10.1111/j.1478-3231.2011.02699.x
  39. Owsianka, A. M., Tarr, A. W. and Keck, Z. Y. : Broadly neutralizing human monoclonal antibodies to the hepatitis C virus E2 glycoprotein. J. Gen. Virol. 89, 6536 (2008).
  40. Giang, E., Dorner, M. and Prentoe, J. C. : Human broadly neutralizing antibodies to the envelope glycoprotein complex of hepatitis C virus. PNAS 109, 6205 (2012). https://doi.org/10.1073/pnas.1114927109
  41. Kong, L., Giang, E. and Robbins, J. B. : Structural basis of hepatitis C virus neutralization by broadly neutralizing antibody HCV1. Proc. Natl. Acad. Sci. USA 109, 9499 (2012). https://doi.org/10.1073/pnas.1202924109
  42. Barnes, E., Folgori, A., Capone, S., Swadling, L. and Aston, S. : Novel adenovirus-based vaccines induce broad and sustained T cell responces to HCV in man. Sci. Transl. Med. 4, 115ra1 (2012).
  43. Greenhill, Hepatitis: HCV vaccine is successful in phase I study in healthy volunteers. Nat. Rev. Gastroenterol Hepatol. 9, 126 (2012).
  44. Harrison, Viral disease: Steps towards an HCV vaccine. Nat. Rev. Drug Discov. 11, 187 (2012). https://doi.org/10.1038/nrd3687
  45. Sharma SD, Hepatitis C virus: Molecular biology and current therapeutic options. Indian J. Med. Res. 131, 17 (2010).
  46. Leung, D., Abbenante, G. and Fairlie, D. P. : Protease inhibitors: Currenr status and future prospects. J. Med. Chem. 43, 305 (2000). https://doi.org/10.1021/jm990412m
  47. Hofmann, W. P. and Zeuzem, S. : A new standard of care for the treatment of chronic HCV infection. Nat. Rev. Gastroenterol. and Hepatol. 8, 257 (2011). https://doi.org/10.1038/nrgastro.2011.49
  48. Proceedings of the 5th Paris Hepatitis Conference. International Conference of the Management of Patients with Viral Hepatitis: Special Edition Hepatitis C. Liver International 32, 1 (2012).
  49. Jana Schuetter : New drugs hit the target. Nature 474, 55 (2011).
  50. Rice : New insights into HCV replication: potential antiviral targets. Topics in Antiviral Med. 19, 117 (2011).
  51. Manja : New Immunomodulators. 1st Global Work Shop on HCV Therapy Advances, 119-10, Oct. 2011, Madrid, Spain.
  52. www.hcvdrug.com. : Hepatitis C New Drug Pipeline; Clayden : Hepatitis C drug development goes from pony ride to rocket launch, TAG 2012 Pipeline Report, pp. 137-184 (2012).
  53. Jean-Michel Pawlotsky : New Antiviral Agents for Hepatitis C, F1000 Biology Reports 2012, 4:5.
  54. Muir, A. J., Shiffman, M. L., Zaman, A. and Yoffe, B. : Phase 1b study of pegylated interferon lambda 1 with or without ribavirin in patients with chronic genotype 1 hepatitis C virus infection. Hepatology 52, 822 (2010). https://doi.org/10.1002/hep.23743
  55. Guidance for Industry, Chronic Hepatitis C Virus Infection: Developing Directing-Acting Antiviral Agents for treatment, U.S. FDA, Center for Drug Evaluation and Research.
  56. Pham, L. V., Ngo, H. T., Lim, Y. S. and Hwang, S. B. : Hepatitis C virus non-structural 5B protein interacts with cyclin A2 and regulates viral propagation. Journal of Hepatology 57, 960 (2012). https://doi.org/10.1016/j.jhep.2012.07.006
  57. Park, J., Kang, W., Ryu, S.-W., Kim, W.-I., Chang, D.-Y. and Lee, D. H. : Hepatitis C virus infection enhances TNF-${\alpha}$ induced cell death via suppression of NF-${\kappa}B$. Hepatology 56, 831 (2012). https://doi.org/10.1002/hep.25726
  58. Jeong : CD11b+GDr1+bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice. Hepatology, Accepted manuscript online: 27 APR (2012).
  59. Eskandar Hajiani, Seyed Mohammad Alavi : A review on epidemiology, diagnosis and treatment of hepetitis D virus infection. Jundishapur J. of Microbiology 4, s1 (2011).
  60. V Chandra, S Taneja, M Kalia : Molecular biology and pathogenesis of hepatitis E virus. J. Biosci. 33, 451 (2008). https://doi.org/10.1007/s12038-008-0064-1
  61. Feng-Cai Zhu, Jun Zhang, Xue-Feng Zhang, Cheng Zhou : Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. The Lancet 376, 895 (2010). https://doi.org/10.1016/S0140-6736(10)61030-6
  62. Shrestha, M. P., Scott, R. Mc., Joshi, D. M., Mammen, M. P., Welsch1, C. and Jesudian, A. : Safety and efficacy of a recombinant hepatitis E vaccine. N. Engl. J. Med. 356, 895 (2007). https://doi.org/10.1056/NEJMoa061847
  63. Fellay, G. D. : Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 46, 399 (2009).
  64. Kimer, N., Dahl, E. K., Gluud, L. L. and Krag, A. : Antiviral therapy for prevention of hepatocellular carcinoma. BMJ Open 2 (2012).
  65. Jahan, S., Ashfa, U. A., Qasim, M., Khaliq, S., Saleem and Nadeem, M. J. : Hepatitis C virus to hepatocellular carcinoma. Infectious Agents and Cancer 7:2 (2012). https://doi.org/10.1186/1750-9378-7-2
  66. Tran, G. : The role of hepatitis C virus in the pathogenesis of hepatocellular carcinoma. BioscienceHorizones 1, 167 (2008).
  67. Welsch, C., Jesudian, A. and Zeuzem, S. : New directacting antiviral agents for the treatment of hepatitis C virus infection and perspectives. Gut 61, i36 (2012). https://doi.org/10.1136/gutjnl-2012-302144