DOI QR코드

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Virological Response to Conventional Interferon Therapy Combined with Ribavirin against Various HCV Genotypes in Khyber Pakhtunkhwa, Pakistan

  • 발행 : 2016.05.01

초록

Background: Response to antiviral therapy has been linked to different genotypes and this impacts on clinical management. Data on general responses to standard interferon (IFN) against HCV infection exists but little is known regarding HCV genotype specific responses. Purpose: Therefore, we attempted to determine genotype specific responses of chronic HCV patients, having different HCV genotypes, to standard IFN and ribavirin combination therapy administered for a period of six months in Kybher Pakhtunkhwa province of Pakistan. Materials and Methods: HCV genotype was determined for all serum samples. Each patient received standard IFN combination therapy with ribavirin administered at dose of 3 MIU three times a week and 800-1200 mg/day, respectively, for a period of six months. After completion of this therapy, PCR was performed for all course completed subjects. Results: Out of total 51 selected patients the most abundant genotypes were 3a (49.0%) and 1a (21.6%) followed by 3b (9.8%), 1b (7.84%), 2a (7.84%) and untypable (3.94%). Moast responsive genotypes were 2a followed by 3a, with end of treatment responses of 77.7%, and 72.2%. Responses for 3b, 1b and untypable were 66.7%, 33.3% and 0%, respectively. Conclusions: IFN response is efficient in case of 2a and 3a genotypes while in case of untypable genotypes, further categorization is required to know about genomic sequences and to adopt some new regimes against these genotypes.

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참고문헌

  1. Alessandra M, Angelo A, (2010). Tailoring the length of antiviral treatment for hepatitis C. Gut, 59, 1-5. https://doi.org/10.1136/gut.2009.179606
  2. Alter M J (1997). The epidemiology of acute and chronic hepatitis C. Clin Liver Disease, 1, 559-68. https://doi.org/10.1016/S1089-3261(05)70321-4
  3. Amoroso P, Rapicetta M, Tosti M E, et al (1998). Correlation between virus genotype and chronicity rate in acute hepatitis C. J Hepatol, 28, 939-944. https://doi.org/10.1016/S0168-8278(98)80340-1
  4. Berg T, Von W M, Hinrichsen H, et al (2003). Comparison of 48 or 72 weeks of treatment with peginterferon alfa-2a (40KD) (Pegasys) plus ribavirin (Copegus) in treatment-naive patients with chronic hepatitis C infected with HCV genotype 1. Hepatology, 38, 317A. https://doi.org/10.1016/S0270-9139(03)80371-3
  5. Bukh J, Miller RH, Purcell RH (1995). Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. Semin Liver Disease, 15, 41-63. https://doi.org/10.1055/s-2007-1007262
  6. Buti M, Valdes A, Sanchez-Avila F, et al (2003). Extending combination therapy with peginterferon alfa-2b plus ribavirin for genotype 1 chronic hepatitis C late responders: a report of 9 cases. Hepatology, 37, 1226-7. https://doi.org/10.1053/jhep.2003.50107
  7. Charlton M (2001). Hepatitis C infection in liver transplantation. Am J Transplant, 1, 197-203. https://doi.org/10.1034/j.1600-6143.2001.001003197.x
  8. Dalgard O, Bjoro K, Ring-Larsen H, et al (2008). PEGylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology, 47, 35-42.
  9. Enomoto N, Sakuma I, Asahina Y, et al (1996). Mutations in the nonstructural protein 5A gene and response to interferon in patients with chronic hepatitis C virus 1b infection. New Engl J Med, 334, 77-81. https://doi.org/10.1056/NEJM199601113340203
  10. Fried M W, Shiffman M L, Reddy K R, et al (2002). Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. New Engl J Med, 347, 975-82. https://doi.org/10.1056/NEJMoa020047
  11. Hadziyannis S J, Sette H, Morgan T R, et al (2004). Peginterferon 2a and ribavirin combination therapy in chronic hepatitis C: A randomized study of treatment duration and ribavirin dose. Ann Int Med, 140, 346-55. https://doi.org/10.7326/0003-4819-140-5-200403020-00010
  12. Hasan F, Asker H, Al-Khaldi J, et al (2004). Peg interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4. Am J Gastroenterol, 99, 1733-1737. https://doi.org/10.1111/j.1572-0241.2004.40077.x
  13. Idrees M, Riazuddin S (2008). Frequency distribution of hepatitis C virus genotypes in different geographical regions of Pakistan and their possible routes of transmission. BMC Infectious Diseases, 8, 69. https://doi.org/10.1186/1471-2334-8-69
  14. Iqbal M, (2003). An update on the management of hepatitis C. J Coll Physicians Surgeon Pakistan, 13, 477-482.
  15. Latif R, Imtiaz K, Aqib I, et al (2011). Active hepatitis C infection and HCV genotypes prevalent among the IDUs of Khyber Pakhtunkhwa. Virology J, 8, 327. https://doi.org/10.1186/1743-422X-8-327
  16. Lindsay KL, Trepo C, Heintges T, et al (2001). A randomized, double-blind trial comparing pegylated interferon alfa-2b to interferon alfa-2b as initial treatment for chronic hepatitis C. Hepatology, 34, 395-403.
  17. Manns M P, McHutchison J G, Gordon SC, et al (2001). Peg interferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet, 358, 958-65. https://doi.org/10.1016/S0140-6736(01)06102-5
  18. Martinot-Peignoux M, Marcellin P, Pouteau M et al (1995). Pretreatment serum hepatitis C virus RNA levels and hepatitis C virus genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology, 22, 1050-60.
  19. McHutchison J G, Gordon SC, Schiff ER, et al, (1998). Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. New Engl J Med, 339, 1485-92. https://doi.org/10.1056/NEJM199811193392101
  20. Mitchell L. Shiffman, M.D., Fredy S, et al (2007). Peg interferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. New Engl J Med, 357, 124-13. https://doi.org/10.1056/NEJMoa066403
  21. Moribe T, Hayashi N, Kanazawa Y, et al (1995). Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy. Gastroenterology, 108, 789-95. https://doi.org/10.1016/0016-5085(95)90452-2
  22. Neumann AU, Lam NP, Dahari H, et al (2000). Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J Infectious Dis, 182, 28-35. https://doi.org/10.1086/315661
  23. Ohno T, Mizokami M, Wu R, (1997): New hepatitis C virus genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Microbiol, 35, 201-207.
  24. Okada S, Akahane Y, Suzuki H, et al (1992). The degree of variability in the amino terminal region of the E2/NS1 protein of hepatitis C virus correlates with responsiveness to interferon therapy in viremia patients. Hepatology, 16, 619-24. https://doi.org/10.1002/hep.1840160302
  25. Pawlotsky J M (2002). Use and interpretation of virological tests for hepatitis C. Hepatology, 36, 65-73. https://doi.org/10.1002/hep.1840360709
  26. Poynard T, Marcellin P, Lee S S, et al (1998). Randomized trial of interferon alpha2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alpha2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet, 352, 1426-32. https://doi.org/10.1016/S0140-6736(98)07124-4
  27. Puro V, Petrosillo N, Ippolito G (1995). Occupational Hepatitis C virus infection in Italian health care workers. Am J Public Health, 85, 1272-5. https://doi.org/10.2105/AJPH.85.9.1272
  28. Sarwar S, Butt AK, Khan AA (2006). Serum alanine aminotransferase level and response to Interferon-Ribavirin combination therapy in patients with chronic hepatitis C. J Coll Physicians Surgeon Pakistan, 16, 460-463.
  29. Shi PY (2012). Molecular Virology and Control of Flaviviruses. Caister Academic Press. ISBN: 978-1-904455-92-9.
  30. Simmonds P (1999). Viral heterogeneity of the hepatitis C virus. J Hepatol, 31, 54-60. https://doi.org/10.1016/S0168-8278(99)80375-4
  31. Wasley A, Alter MJ (2000). Epidemiology of hepatitis C: geographic differences and temporal trends. Semin Liver Disease, 20, 1-16. https://doi.org/10.1055/s-2000-9506
  32. Yu ML, Chuang WL (2009), Treatment of chronic hepatitis C in Asia: when East meets west. J Gastroenterol Hepatol, 24, 336-45. https://doi.org/10.1111/j.1440-1746.2009.05789.x
  33. Zein N N, Rakela J, Krawitt E L, et al (1996). Hepatitis C virus genotypes in the United States: epidemiology, pathogenicity, and response to interferon therapy. Ann Int Med, 125, 634-9. https://doi.org/10.7326/0003-4819-125-8-199610150-00002
  34. Zeuzem S, Feinman S V, Rasenack J, et al (2000). Peg interferon alfa-2a in patients with chronic hepatitis C. New Engl J Med, 343, 1666-72. https://doi.org/10.1056/NEJM200012073432301
  35. Zeuzem S, Herrmann E, Lee J H, et al (2001). Viral kinetics in patients with chronic hepatitis C treated with standard or peginterferon alpha2a. Gastroenterology, 120, 1438-47. https://doi.org/10.1053/gast.2001.24006