Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Genotypes of Hepatitis C Virus in Relapsed and Non-respondent Patients and their Response to Anti-Viral Therapy in District Mardan, Khyber Pakhtunkhawa, Pakistan

  • Akhtar, Noreen (Department of Microbiology, Faculty of Life Science, Abasyn University) ;
  • Bilal, Muhammad (Department of Microbiology, Faculty of Life Science, Abasyn University) ;
  • Rizwan, Muhammad (Department of Microbiology, Faculty of Life Science, Abasyn University) ;
  • Khan, Muhammad Asif (Department of Pathology, District Head Quarter Hospital Mardan, KPK) ;
  • Khan, Aurangzeb (Department of Pathology, District Head Quarter Hospital Mardan, KPK)
  • Published : 2015.03.04
Download PDF
⟨ Previous Next ⟩

Abstract

Hepatitis C is a blood-borne infectious disease of liver, caused by a small enveloped, positive-single stranded RNA virus, called the hepatitis C virus (HCV). HCV belongs to the Flaviviridae family and has 6 genotypes and more than 100 subtypes. It is estimated that 185 million people are infected with HCV worldwide and 5% of these are in Pakistan. The study was designed to evaluate different genotypes of HCV circulating in District Mardan and to know about the behavior of these genotypes to different anti-viral regimes. In this study 3,800 patients were exposed to interferon alfa-2a plus Ribavirin treatment for 6-months and subjected to real-time PCR to check the viral response. Among these 3,677 (97%) patients showed no detectable HCV RNA while 123 (3%) patients (non-responders) remained positive for HCV RNA. Genotypes of their analyzed showed that most of them belonged to the 3a genotype. Non-responders (123) and relapsed (5) patients were subjected to PEG-interferon and Ribavirin therapy for next 6 months, which resulted into elimination of HCV RNA from 110 patients. The genotypes of the persisting resistant samples to anti-viral treatment were 3b, 2a, 1a and 1b. Furthermore, viral RNA from 6 patients remained un-typed while 4 patients showed mixed infections. HCV was found more resistant to antiviral therapy in females as compared to mals. The age group 36-45 in both females and males was found most affected by infection. In general 3a is the most prevalent genotype circulating in district Mardan and the best anti-viral therapy is PEG-interferon plus Ribavirin but it is common practice that due to the high cost patients receive interferon alfa-2a plus Ribavirin with consequent resistance in 3% patients given this treatment regime.

Keywords

References

  1. Afridi S, Naeem M, Hussain A, et al (2009). Prevalence of hepatitis C virus (HCV) genotypes in Balochistan. Mol Biol Rep, 36, 1511-4. https://doi.org/10.1007/s11033-008-9342-0
  2. Afridi SQ, Zahid MN, Shabbir MZ, et al (2013). Prevalence of HCV genotypes in district Mardan. Virol J, 10, 10-90. https://doi.org/10.1186/1743-422X-10-10
  3. Ahmad B, Ali S, Ali I, Azam S, Bashir S (2012). Response rates of standard interferon therapy in chronic HCV patients of Khyber Pakhtunkhwa (KPK). Virol J, 9,18. https://doi.org/10.1186/1743-422X-9-18
  4. Ahmad B, Ali S, Ali I et al (2013). Conventional Interferon Therapy Response among Chronic HCV Patients in Khyber Pakhtunkhwa. J Infect Dis Ther, 1,104.
  5. Alter MJ, Margolis HS, Krawczynski K, et al (1992). The natural history of community-acquired hepatitis C in the United States. N Engl J Med, 327, 1899-905. https://doi.org/10.1056/NEJM199212313272702
  6. Alter MJ (2007). Epidemiology of hepatitis C virus infection. World J Gastroenterol, 13, 2436-41. https://doi.org/10.3748/wjg.v13.i17.2436
  7. Arshad A, Arshad M, Pervaiz R, et al (2012). Prevalance of Active Hepatitis-C infection in the general population of district Mardan, Khyber Pakhtunkhwa. Pakistan J Public Health Biological Sci, 1, 3-8.
  8. Butt AA (2005). Hepatitis C virus infection: the new global epidemic. Expert Rev Anti Infect Ther, 3, 241-9. https://doi.org/10.1586/14787210.3.2.241
  9. Bowden DS, Berzsenyi MD (2006). Chronic hepatitis C virus infection: genotyping and its clinical role. Future Microbiol, 1, 103-12. https://doi.org/10.2217/17460913.1.1.103
  10. Castillo I, Bartolome J, Quiroga JA, Barril G, Carreno V (2010). Diagnosis of occult hepatitis C without the need for a liver biops. J Med Virol, 82, 1554-9. https://doi.org/10.1002/jmv.21866
  11. Frank C, Mohamed MK, Strickland GT, et al (2000).The role of parenteral antischistosomal therapy in the spread of hepatitis C virus in Egypt. Lancet, 35, 5887-91.
  12. Fried MW, Shiffman ML, Reddy KR, et al (2002). Peginterferon alfa-2a plus ribavirin for the chronic hepatitis C virus infection. N Engl J Med, 347, 975-82. https://doi.org/10.1056/NEJMoa020047
  13. Friedrich TC, Dodds EJ, Yant LJ, et al (2004). Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nat Med, 10, 275-81. https://doi.org/10.1038/nm998
  14. Ghany MG, Strader DB, Thomas DL, Seeff LB (2009). American association for the study of liver diseases. diagnosis, management, and treatment of hepatitis C: an update. Hepatology, 49, 1335-74. https://doi.org/10.1002/hep.22759
  15. Gretch DR (1997). Diagnostic tests for hepatitis C. Hepatology, 299, 435-75.
  16. Iancu LS (2001). Diagnostic strategies in hepatitis C virus infection. Rev Med Chir Soc Med Nat Iasi, 105, 37-42.
  17. Kanda T, Yokosuka O, Omata M (2013). Hepatitis C Virus and Hepatocellular Carcinoma. Biology, 2, 304-16. https://doi.org/10.3390/biology2010304
  18. Khan MSA, Khalid M, Ayub N, Javed M (2004). Seroprevalence and risk factors of Hepatitis C virus (HCV) in Mardan, N.W.F.P. Rawal Med J, 29, 57-60.
  19. Koziel M, Peters M (2007). Viral hepatitis in HIV infection. N Engl J Med, 356, 1445-54. https://doi.org/10.1056/NEJMra065142
  20. Levrero M (2006). Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene, 25, 3834-47. https://doi.org/10.1038/sj.onc.1209562
  21. Lin C, Lindenbach BD, Pragai BM, McCourt DW, Rice CM (1994). Processingin the hepatitis C virus E2-NS2 region: identification of p7 and two distinct E2-specific products with different C termini. J Virol, 68, 5063-73.
  22. Mangia A, Mottola L (2012). What's new in HCV genotype 2 treatment? Liver Int, 1, 135-40.
  23. Manns MP, McHutchison JG, Gordon SC, et al (2001). Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet, 358, 958-65. https://doi.org/10.1016/S0140-6736(01)06102-5
  24. Martinot-Peignoux M, Stern C, Maylin S, et al (2010). Twelve weeks posttreatment follow-up is as relevant as 24 weeks to determine the sustained virologic response in patients with hepatitis C virus receiving pegylated interferon and ribavirin. Hepatology, 51, 1122-6. https://doi.org/10.1002/hep.23444
  25. Michelin BD, Muller Z, Stezl E, et al (2007). Evaluation of the abbott real time HCV assayfor quantificative detection of hepatitis C virus RNA. J Clin Virol, 38, 96-100. https://doi.org/10.1016/j.jcv.2006.11.007
  26. Munaf A, Memon MS, Kumar P, Ahmed S, Kumar MB (2014). Comparison of viral hepatitis-associated hepatocellular carcinoma due to HBV and HCV - cohort from liver clinics in Pakistan. Asian Pac J Cancer Prev, 15, 7563-7. https://doi.org/10.7314/APJCP.2014.15.18.7563
  27. Munir S, Saleem S, Idrees M, et al (2010). Hepatitis C treatment: current and future perspectives. Virol J, 7, 296. https://doi.org/10.1186/1743-422X-7-296
  28. Reed KE, Rice CM (2000). Overview of hepatitis C virus genome structure, polyprotein processing, and protein properties. Curr. Top. Microbiol Immunol, 242, 55-84.
  29. Rockstroh J, Grint D, Boesecke C, et al (2012). Increases in acute hepatitis C (HCV) incidence across Europe: which regions and patient groups are affected? J Int AIDS Soc, 15, 18116.
  30. Sabato MF, Shiffman ML, Langley MR, et al (2007). Comparison of performance characteristics of three real time reverse transcription-PCR test systems for detection and quantification of hepatitis C virus. J Clin Microbiol, 45, 2529-36. https://doi.org/10.1128/JCM.00058-07
  31. Shepherd J, Brodin H, Cave C, et al (2004). Pegylated interferon alpha-2a and -2b in combination with ribavirin in the treatment of chronic hepatitis C : a systematic review and economic evaluation. Health Technol Assess, 8.
  32. Shev S, Hermodsson S, Lindholm A, et al (1995). Risk factor exposure among hepatitis C virus RNA positive Swedish blood donors the role of parenteral and sexual transmission. Scand J Infect Dis, 27, 99-104. https://doi.org/10.3109/00365549509018987
  33. Tang H, Grise H (2009). Cellular and molecular biology of HCV infection and hepatitis. Clin Sci, 117, 49-65. https://doi.org/10.1042/CS20080631
  34. Tang H, Grise H (2009). Cellular and molecular biology of HCV infection and hepatitis. Clin Sci, 117, 49-65. https://doi.org/10.1042/CS20080631

Cited by

  1. HCV, Interferon Therapy Response, Direct Acting Antiviral Therapy Revolution and Pakistan: Future Perspectives vol.16, pp.13, 2015, https://doi.org/10.7314/APJCP.2015.16.13.5583
  2. Incidence of Active HCV infection amongst Blood Donors of Mardan District, Pakistan vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.235
  3. Prevalence and Treatment of Untypable HCV Variants in Different Districts of Punjab, Pakistan vol.31, pp.6, 2018, https://doi.org/10.1089/vim.2017.0167