RESPONSE OF DIFFERENT HCV GENOTYPES TO INTERFERON THERAPY IN DIFFERENT AGE GROUPS OF CHRONIC HEPATITIS-C PATIENTS
AbstractBackground: Although new Pegylated Interferon is available, yet the conventional Interferon with the combination of Ribavirin is still the therapy of choice to treat the Hepatitis C patients. This study was conducted to investigate the response of different HCV genotypes in different age groups of chronic Hepatitis C patients treated with conventional Interferonα-2b (IFNα-2b) plus Ribavirin (RBV). Methods: In this cross sectional observational study a total of 520 Hepatitis C patients infected with different HCV genotypes meeting the study criteria were included from August 2010 to January 2013. End of treatment response (ETR), sustained virological response (SVR) and the association of patient’s age with treatment response were evaluated. ETR and SVR were defined as absence of HCV RNA and normal ALT level at the end of therapy and 12 months after the termination of therapy respectively. Results: Out of 520 cases 388 (74.62%) showed ETR. The SVR was observed in 290 (89.23%) out of 325 ETR responders. ETR was higher in males (76.14%) than females (72.77%) while the SVR was almost same in both sex. The highest ETR was noted in genotype 3 (81.15%). The old patients exhibited lower ETR and SVR than youngers in the present study. Conclusions: The properly managed conventional Interferon therapy was effective for Hepatitis C patients infected with genotype 2 and 3 with age <40 years as compared to those patients infected with genotype-1 and 4 or had age >40 years.Keywords: Chronic Hepatitis C, Interferon plus Ribavirin, ETR, SVR
Sarasin-Filipowicz M, Oakeley EJ, Duong FH, Christen V, Terracciano L, Filipowicz W, et al. Interferon signaling and treatment outcome in chronic Hepatitis C. Proc Natl Acad Sci U S A 2008;105:7034–9.
Manns MP, McHutchison LG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. PegInterferon alfa-2b plus Ribavirin compared with Interferon alfa-2b plus Ribavirin for initial treatment of chronic Hepatitis C: a randomised trial. Lancet 2001;358:958–65.
Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. PegInterferon alfa-2a plus Ribavirin for chronic Hepatitis C virus infection. N Engl J Med 2002;347:975–82.
Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, et al. PegInterferon-alpha2a and Ribavirin combination therapy in chronic Hepatitis C: a randomized study of treatment duration and Ribavirin dose. Ann Intern Med 2004;140:346–55.
Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC Jr, Perrillo RP, et al. Treatment of chronic Hepatitis C with recombinant Interferon alpha. A multi-center randomized, controlled trial. Hepatitis interventional therapy group. N Engl J Med 1989;321:1501–6.
Davis GL, Wong JB, McHutchison JG, Manns MP, Harvey J, Albrecht J. Early virologic response to treatment with pegInterferon alfa-2b plus Ribavirin in patients with chronic Hepatitis C. Hepatology 2003;38:645–52.
Vigani AG, Goncales ES, Pavan MH, Genari F, Tozzo R, Lazarini MS, et al. Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3. Braz J Infect Dis 2012;16:232–6.
Hadziyannis SJ, Cheinquer H, Morgan T. Peg Interferon alpha-2a (40 KD) in combination with Ribavirin efficacy and safety results from phase 3, randomized double blind, multicenter study examining effect of duration and Ribavirin dose. J Hepatol 2002;36(1):3–14.
Karayiannis P. The Hepatitis C virus NS3/4A protease complex interferes with pathways of the innate immune response. J Hepatol 2005;43:743–5.
Zuberi BF, Zuberi FF, Memon SA, Qureshi MH, Ali SZ, Afsar S. Sustained virological response based on rapid virological response in genotype-3 chronic Hepatitis C treated with standard Interferon in the Pakistani population. World J. Gastroenterol 2008;14:2218–21.
Peribanez-Gonzalez M, da Silva MH, Vilar FC, Seixas-Santos Nastri AC, Ferriera PA, Focaccia R, Correa MCM. Response predictors and clinical benefits of hepatitis C retreatment with pegylated interferon and ribavirin in HIV/HCV coinfection. Ann Hepatol 2013;12:228–35.
Idrees M, Riazuddin S. A study of best positive predictors for sustained virologic response to Interferon alpha plus Ribavirin therapy in naive chronic Hepatitis C patients. BMC Gastroenterol 2009;9:5.
Iqbal S, Rehman K, Dogar ZH, Bashir S, Akhtar MS. Sustained biochemical and virological response of different HCV genotypes to Interferon-alpha plus Ribavirin combination therapy. Pharmacologyonline 2010;2:161–9.
de Careaga BO. Predictive factors for response to treatment of chronic Hepatitis C. Ann Hepatol 2006;5:S24–8.
Hofmann WP, Zeuzem S, Sarrazin C. Hepatitis C virus resistance mechanisms to Interferon- α based antiviral therapy. J Clin Virol 2005;32:86–91.
Zeuzem S, Diago M, Gane E, Reddy KR, Pockros P, Prati D, et al. PegInterferon alfa-2a (40 kilodaltons) and Ribavirin in patients with chronic Hepatitis C and normal aminotransferase levels. Gastroenterology 2004;127:1724–32.
Ohno T, Mizokami M, Saleh MM, Ohba K, Orito E, Mukaide M, et al. New Hepatitis C virus (HCV) genotyping system that allows for identification of HCV genotypes 1a, 1b, 2a, 2b, 3a, 3b, 4, 5a, and 6a. J Clin Micro 1997;35:201–7.
McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic Hepatitis C. Gastroenterol 2002;123:1061–9.
Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Costelnau C, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic Hepatitis C and sustained response to Interferon-alpha treatment. Ann Intern Med 1997;127:875–81.
Ahmed W, Arif A, Qureshi H, Alam SE, Ather R, Fariha S, et al. Factors influencing the response of Interferon therapy in chronic Hepatitis C patients. J Coll Physicians Surg Pak 2011;21:69–73.
Shaikh WM, Shaikh MA, Solangi GA, Zuberi BF. Role of Interferon and Interferon plus Ribavirin in the management of chronic Hepatitis C. J Coll Physicians Surg Pak 2002;12:609–12.
Farooqi JI, Farooqi RJ. Efficacy of conventional Interferon alpha-2b plus Ribavirin combination in the treatment of chronic Hepatitis C naive patients. Rawal Med J 2005;30:9–11.
Manns MP, Wedemeyer H, Cornberg M. Treating viral Hepatitis C: efficacy, side effects and complications. Gut 2006;55:1350–9.
Herrine SK, Rossi S Navarro VJ. Management of patients with chronic Hepatitis C infection. Clin Exp Med 2006;6:20–6.
Nadeem A, Hussain MM, Aslam M, Hussain T, Butt IF, Ali Khan S, et al. Association of response to combined Interferon alpha-2b and Ribavirin therapy in patients of chronic Hepatitis C with serum alanine aminotransferase levels and severity of the disease on liver biopsy. J Ayub Med Coll Abbottabad 2009;21(2):103–6.
Mahsud I, Khan RD, Khan M, Hameed K. Response of Hepatitis C patients to alpha Interferon and Ribavirin combination therapy. Gomal J Med Sci 2008;6(2):65–8.
Khokhar N. Late relapse in chronic hepatitis C after sustained viral response to interferon and Ribavirin. J Gastroenterol Hepatol 2004;19:471–2.
Jadoon SM, Jadoon S, Muhammad I. Response to standard Interferon a2b and Ribavirin combination therapy in chronic Hepatitis C treatment naive patients. J Ayub Med Coll Abbottabad 2010;22(4):164–6.
Bhutta S, Wasimuddin, Muzamil J. Short duration therapy with standard Interferon and Ribavirin in chronic Hepatitis C genotype 3a patients. Is it too short? Ann Pak Inst Med Sci 2011;7(2):86–9.
Marcellin P, Boyer N, Gervais A, Martinot M, Pouteau M, Castelnau C, et al. Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic Hepatitis C and sustained response to Interferon-alpha therapy. Ann Int Med 1997;127:875–81.
Kalantari H, Kazemi F, Minakari M. Efficacy of triple therapy with Interferon alpha-2b, Ribavirin and Amantadine in the treatment of naive patients with chronic Hepatitis C. J Res Med Sci 2007;12:178–85.
Muhammad N, Jan MA, Rahman N. Outcome of combine interferon-ribavirin in the treatment of chronic Hepatitis C. J Coll Physicians Surg Pak 2004; 14:651-653.
Lai MY, Kao JH, Yang PM, Wang JT, Chen PJ, Chan KW, et al. Long term efficacy of Ribavirin plus Interferon alpha in the treatment of chornic Hepatitis C. Gastrointerology 1996;111:1307–12.
John M, Flexman J, French MA. Hepatitis C virus-associated Hepatitis following treatment of HIV-infected patients with HIV protease inhibitors: an immune restoration disease. AIDS 1998;12:2289–93.
Idrees M, Riazuddin S. Frequency distribution of Hepatitis C virus genotypes in different geographical regions of Pakistan and their possible routes of transmission. BMC Infect Dis 2008;8:69.
Ahmad W, Ijaz B, Javed FT, Jahan S, Shahid I, Khan FM, et al. HCV genotype distribution and possible transmission risks in Lahore, Pakistan. World J Gastroenterol 2010;16:4321–8.
Iqbal S, Ahmad R, Yousaf MH, Mumtaz A, Amine D, Rasool G, et al. Assessment of major genotypes and subtypes of Hepatitis C virus. Professional Med J 2007;14:266–71.
Burguete-Garcia AI, Conde-Gonzlez CJ, Jimenez-Mendez R, Juarez-Diaz Y, Meda-Monzon E, Torres-Poveda K, et al. Hepatitis C sero-prevalence and correlation between viral load and viral genotype among primary care clients in Mexico. Salud Publica Mex 2011;53(Suppl 1):S7–12.
Eriksen MB, Jorgensen LB, Krarup H, Laursen AL, Christensen PB, Moller A, et al. Molecular and epidemiological profiles of Hepatitis C virus genotype 4 in Denmark. J Med Virol 2010;82:1869–77.
Haushofer, AC, Kopty C, Hauer R, Brunner H, Halbmayer WM. HCV genotypes and age distribution in patients of Vienna and surrounding areas. J Clin Virol 2001;20(1-2):41–7.
Antonucci G, Angeletti C, Vairo F, Longo MA, Girardi E. Age and prediction of sustained virological response to Hepatitis C virus (HCV) infection treatment based on 28-day decrease in HCV RNA levels. J Infect Dis 2009;200:1484–5.
Shiffman ML, Mihas AA, Millwala F, Sterling RK, Luketic VA, Stravitz RT, et al. Treatment of chronic Hepatitis C virus in African Americans with genotypes 2 and 3. Am J Gastroenterol 2007;102:761–6.
Bakr I, Rekacewicz C, El Hosseiny M, Ismail S, El Daly M, El-Kafrawy S, et al. Higher clearance of Hepatitis C virus infection in females compared with males. Gut 2006;55:1183–7
Shindo M, Arai K, Sokawa Y, Okuno T. Hepatic Hepatitis C virus RNA as a predictor of a long-term response to Interferon-alpha therapy. Ann Intern Med 1995;122:586–91.
Kjaergard LL, Krogsgaard K, Gluud C. Interferon alfa with or without Ribavirin for chronic Hepatitis C: systematic review of randomised trials. BMJ 2001;323:1151–5.
Attaullah S, Khan S, Ali I. Hepatitis C virus genotypes in Pakistan: a systemic review. Virol J 2011;8:433–40.
Chung RT, Monto A, Dienstag JL, Kaplan LM. Mutations in the NS5A region do not predict interferon-responsiveness in american patients infected with genotype 1b hepatitis C virus. J Med Virol 1999;58:353–8.
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.