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Improved Sustained Virological Response Following Treatment with Pegylated-Interferon Alpha-2b Compared with Alpha-2a, Both with Ribavirin, for Chronic Hepatitis C Infection with Genotypes 2 and 3

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DOI: 10.4236/ijcm.2014.53019    2,767 Downloads   4,084 Views  

ABSTRACT

Purpose: The optimal formulation of pegylated interferon a (PEG-IFa) as a part of combination therapy with ribavirin (RBV) is uncertain for patients infected with hepatitis C Genotypes 2 and 3. Methods: A multivariate analysis of prospectively collected treatment data from two tertiary centres on 351 treatment na?ve HCV Genotype 2 or 3 patients who received PEG-IFa-2a or b plus ribavirin. Results: Univariate analyses demonstrate that PEG-IFa-2b based on regimens achieved a higher sustained virological response (SVR) than PEG-IFa-2a (77.9% versus 62.0%, P = 0.0012). On multivariate analyses, PEG-IFa-2b appeared superior to PEG-IFa-2a with an odds ratio (OR) and 95% confidence interval (CI95) for SVR of 2.19 (CI95 1.35-3.52, P = 0.0005). Genotype was a significant predictor of outcome in the multivariate model with 80% of Genotype 2 but only 67.7% of Genotype 3 subjects achieving SVR (OR 2.66 [CI95 1.35-5.92]). Increasing age was negatively associated with SVR (OR 0.97 [CI95 0.94-0.99]). Some of the differences in SVR are explained by higher relapse rates with PEG-IFa-2a (P = 0.009). Conclusions: PEG-IFa-2b and RBV achieve higher SVR rates than PEG-IFa-2a and RBV in Genotypes 2 and 3 chronic HCV infections. There is less relapse with PEG-IFa-2b. Genotype 2 infections are considerably easier to cure. SVR is higher in younger patients. These findings should influence a choice of PEG-IFa in the era of direct acting anti-viral drugs in therapy of Genotypes 2 and 3.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

L. Mollison, L. Manning, S. Miczkova and W. Cheng, "Improved Sustained Virological Response Following Treatment with Pegylated-Interferon Alpha-2b Compared with Alpha-2a, Both with Ribavirin, for Chronic Hepatitis C Infection with Genotypes 2 and 3," International Journal of Clinical Medicine, Vol. 5 No. 3, 2014, pp. 111-117. doi: 10.4236/ijcm.2014.53019.

References

[1] D. Lavanchy, “The Global Burden of Hepatitis C. Liver International,” Official Journal of the International Association for the Study of the Liver, Vol. 29, Suppl. 1, 2009, pp. 74-81.
[2] Digestive Health Foundation, “Facts about Hepatitis C,” The Gastroenterological Society of Australia, 2007.
[3] World Health Organization (WHO), “Hepatitis C fact sheet,” World Health Organization, Geneva, 2011.
[4] J. H. Hoofnagle, K. D. Mullen, D. B. Jones, V. Rustgi, A. Di Bisceglie, M. Peters, J. G. Waggoner, Y. Park and E. A. Jones, “Treatment of Chronic Non-A, Non-B Hepatitis with Recombinant Human Alpha Interferon. A Preliminary Report,” The New England Journal of Medicine, Vol. 315, No. 25, 1986, pp. 1575-1578.
http://dx.doi.org/10.1056/NEJM198612183152503
[5] J. G. McHutchison, S. C. Gordon, E. R. Schiff, M. L. Shiffman, W. M. Lee, V. K. Rustgi, Z. D. Goodman, M.-H. Ling, S. Cort and J. K. Albrecht, for the Hepatitis Interventional Therapy Group, “Interferon Alfa-2b alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C. Hepatitis Interventional Therapy Group,” The New England Journal of Medicine, Vol. 339, No. 21, 1998, pp. 1485-1492.
http://dx.doi.org/10.1056/NEJM199811193392101
[6] T. Poynard, P. Marcellin, S. S. Lee, C. Niederau, G. S., Minuk, G. Ideo, et al., “Randomised 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,” International Hepatitis Interventional Therapy Group (IHIT),” Lancet, Vol. 352, No. 9138, 1998, pp. 1426-1432. http://dx.doi.org/10.1016/S0140-6736(98)07124-4
[7] K. L. Lindsay, C. Trepo, T. Heintges, M. L. Shiffman, S. C. Gordon, J. C. Hoefs, E. R. Schiff, Z. D. Goodman, M. Laughlin, R. Yao and J. K. Albrecht, “A Randomized, Double-Blind Trial Comparing Pegylated Interferon Alfa2b to Interferon alfa-2b as Initial Treatment for Chronic Hepatitis C,” Hepatology, Vol. 34, No. 2, 2001, pp. 395-403. http://dx.doi.org/10.1053/jhep.2001.26371
[8] M. Simin, J. Brok, D. Stimac, C. Gluud and L. L. Gluud, “Cochrane Systematic Review: Pegylated Interferon plus Ribavirin vs. Interferon plus Ribavirin for Chronic Hepatitis C,” Alimentary Pharmacology & Therapeutics, Vol. 25, No. 10, 2007, pp. 1153-1162.
http://dx.doi.org/10.1111/j.1365-2036.2007.03294.x
[9] M. P. Manns, J. G. McHutchison, S. C. Gordon, V. K. Rustgi, M. Shiffman, R. Reindollar, 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, Vol. 358, 9286, 2001, pp. 958-965.
http://dx.doi.org/10.1016/S0140-6736(01)06102-5
[10] M. W. Fried, M. L. Shiffman, K. R. Reddy, C. Smith, G. Marinos, F. L. Goncales, Jr., D. Häussinger, M. Diago, G. Carosi, D. Dhumeaux, A. Craxi, A. Lin, J. Hoffman and J. Yu, “Peginterferon Alfa-2a plus Ribavirin for Chronic Hepatitis C Virus Infection,” The New England Journal of Medicine, Vol. 347, No. 13, 2002, pp. 975-982.
http://dx.doi.org/10.1056/NEJMoa020047
[11] S. Zeuzem, T. Berg, B. Moeller, H. Hinrichsen, S. Mauss, H. Wedemeyer, C. Sarrazin, D. Hueppe, E. Zehnter and M. P. Manns, “Expert Opinion on the Treatment of Patients with Chronic Hepatitis C,” Journal of Viral Hepatitis, Vol. 16, No. 2, 2009, pp. 75-90.
http://dx.doi.org/10.1111/j.1365-2893.2008.01012.x
[12] J. H. Hoofnagle, “A Step forward in Therapy for Hepatitis C,” The New England Journal of Medicine, Vol. 360, No. 18, 2009, pp. 1899-1901.
http://dx.doi.org/10.1056/NEJMe0901869
[13] D. M. Jensen, “A New Era of Hepatitis C Therapy Begins,” The New England Journal of Medicine, Vol. 364, No. 13, 2011, pp. 1272-1274.
http://dx.doi.org/10.1056/NEJMe1100829
[14] H. Ochi, C. N. Hayes, H. Abe, Y. Hayashida and T. Uchiyama, N. Kamatani, Y. Nakamura and K. Chayama, “Toward the Establishment of a Prediction System for the Personalized Treatment of Chronic Hepatitis C,” The Journal of Infectious Diseases, Vol. 205, No. 2, 2012, pp. 204-210. http://dx.doi.org/10.1093/infdis/jir726
[15] European Association for the Study of the Liver, “EASL Clinical Practice Guidelines: Management of Hepatitis C Virus Infection,” Journal of Hepatology, Vol. 55, No. 2, 2011, pp. 245-264.
http://dx.doi.org/10.1016/j.jhep.2011.02.023
[16] T. Awad, K. Thorlund, G. Hauser, D. Stimac, M. Mabrouk and C. Gluud, “Peginterferon Alpha-2a Is Associated with Higher Sustained Virological Response than Peginterferon Alfa-2b in Chronic Hepatitis C: Systematic Review of Randomized Trials,” Hepatology, Vol. 51, No. 4, 2010, pp. 1176-1184.
http://dx.doi.org/10.1002/hep.23504
[17] P. Bedossa and T. Poynard, “An Algorithm for the Grading of Activity in Chronic Hepatitis C. The METAVIR Cooperative Study Group,” Hepatology, Vol. 24, No. 2, 1996, pp. 289-293.
http://dx.doi.org/10.1002/hep.510240201
[18] R Development Core Team, “R: A Language and Environment for Statistical Computing,” R Foundation for Statistical Computing, Vienna, 2012.
[19] J. Honaker, G. King and M. Blackwell, “Amelia II: A Program for Missing Data,” Journal of Statistical Software, Vol. 45, No. 7, 2011, pp. 1-47.
[20] D. Ge, J. Fellay, A. J. Thompson, J. S. Simon, K. V. Shianna, T. J. Urban, E. L. Heinzen, P. Qiu, A. H. Bertelsen, A. J. Muir, M. Sulkowski, J. G. McHutchison and D. B. Goldstein1, “Genetic Variation in IL28B Predicts Hepatitis C Treatment-Induced Viral Clearance,” Nature, Vol. 461, No. 7262, 2009, pp. 399-401.
http://dx.doi.org/10.1038/nature08309
[21] V. Suppiah, M. Moldovan, G. Ahlenstiel, T. Berg, M. Weltman, M. L. Abate, M. Bassendine, U. Spengler, G. J Dore, E. Powell, S. Riordan, D. Sheridan, A. Smedile, V. Fragomeli, T. Müller, M. Bahlo, G. J. Stewart, D. R. Booth and J. George for the Hepatitis C Study, “IL28B Is Associated with Response to Chronic Hepatitis C Interferon-Alpha and Ribavirin Therapy,” Nature Genetics, Vol. 41, No. 10, 2009, pp. 1100-1104.
http://dx.doi.org/10.1038/ng.447
[22] Y. Tanaka, N. Nishida, M. Sugiyama, M. Kurosaki, K. Matsuura, N. Sakamoto, et al., “Genome-Wide Association of IL28B with Response to Pegylated InterferonAlpha and Ribavirin Therapy for Chronic Hepatitis C,” Nature Genetics, Vol. 41, No. 10, 2009, pp. 1105-1109.
http://dx.doi.org/10.1038/ng.449
[23] J. G. McHutchison, E. J. Lawitz, M. L. Shiffman, AJ Muir, GW Galler, J McCone, L. M. Nyberg, W. M. Lee, R. H. Ghalib, E. R. Schiff, J. S. Galati, B. R. Bacon, M. N. Davis, P. Mukhopadhyay, K. Koury, S. Noviello, L. D. Pedicone, C. A. Brass, J. K. Albrecht and M. S. Sulkowski for the IDEAL Study Team, “Peginterferon alfa-2b or alfa-2a with Ribavirin for Treatment of Hepatitis C infection,” The New England Journal of Medicine, Vol. 361, No. 6, 2009, pp. 580-593.
http://dx.doi.org/10.1056/NEJMoa0808010
[24] S. M. Alavian, B. Behnava and S. V. Tabatabaei, “The Comparative Efficacy and Safety of Peginterferon Alpha-2a vs. 2b for the Treatment of Chronic HCV infection: A Meta-Analysis,” Hepatitis Monthly, Vol. 10, No. 2, 2010, pp. 121-131.
[25] D. Kershenobich, L. Munoz, R. Male, J. Gaytan and F. Sanchez, “Proceed with Caution: Peginterferon Alpha-2a versus peginterferon alfa-2b in Chronic Hepatitis C. A Systematic REVIEW of Randomized trials,” Hepatology, Vol. 52, No. 6, 2010, pp. 2240-2241.
http://dx.doi.org/10.1002/hep.24025
[26] A. Kolakowska, H. Berok, M. Wasilewski and A. Horbon, “Relevance between Fibrosis and Response to Treatment with Peginterferon Alfa2a vs Alfa2b with Ribavirin in Chronic Hepatitis C Genotype 3 Patients. Randomized open label study,” Hepatology [ABSTRACT], Vol. 48, 2008, p. 1278.
[27] M. Laguno, C. Cifuentes, J. Murillas, S. Veloso, M. Larrousse, A. Payeras, L. Bonet, F. Vidal4, A. Milinkovic1, A. Bassa, C. Villalonga, I. Pérez, C. Tural, M. Martínez-Rebollar, M. Calvo, J. L. Blanco, E. Martínez, J. M. Sánchez-Tapias, J. M. Gatell and J. Mallolas, “Randomized Trial Comparing Pegylated Interferon Alpha-2b versus Pegylated Interferon Alpha-2a, Both plus Ribavirin, to Treat Chronic Hepatitis C in Human Immunodeficiency virus Patients,” Hepatology, Vol. 49, No. 1, 2009, pp. 22-31. http://dx.doi.org/10.1002/hep.22598
[28] G. Scotto, V. Fazio, C. Fornabaio, A. Tartaglia, R. Di Tullio, A. Saracino and G. Angarano, “Peg-Interferon Alpha-2a versus Peg-Interferon Alpha-2b in Nonresponders with HCV Active Chronic Hepatitis: A Pilot Study,” Journal Interferon and Cytokine Research, Vol. 28, No. 10, 2008, pp. 623-629.
http://dx.doi.org/10.1089/jir.2007.0116
[29] M. G. Rumi, A. Aghemo, G. M. Prati, R. D’Ambrosio, MF Donato, R Soffredini, E. Del Ninno, A. Russo and M. Colombo, “Randomized Study of Peginterferon-Alpha2a plus Ribavirin vs Peginterferon-alpha2b plus Ribavirin in Chronic Hepatitis C,” Gastroenterology, Vol. 138, No. 1, 2010, pp. 108-115.
http://dx.doi.org/10.1053/j.gastro.2009.08.071
[30] A. Ascione, M. De Luca, M. T. Tartaglione, F. Lampasi, G. G. Di Costanzo, A. G. Lanza, F. P. Picciotto, G. Marino-Masrsilia, L. Fontanella and G. Leandro, “Peginterferon Alfa-2a plus Ribavirin Is More Effective than Peginterferon Alfa-2b plus Ribavirin for Treating Chronic Hepatitis C virus Infection,” Gastroenterology, Vol. 138, No. 1, 2010, pp. 116-122.
http://dx.doi.org/10.1053/j.gastro.2009.10.005
[31] A. Escudero, F. Rodriguez, M. A. Serra, J. A. Del Olmo, F. Montes and J. M. Rodrigo, “Pegylated α-Interferon-2a Plus Ribavirin Compared with Pegylated α-Interferon-2b Plus Ribavirin for Initial Treatment of Chronic Hepatitis C Virus: Prospective, Non-Randomized Study,” Journal of Gastroenterology and Hepatology, Vol. 23, No. 6, 2008, pp. 861-866.
http://dx.doi.org/10.1111/j.1440-1746.2008.05397.x
[32] D. C. Malone, T. T. Tran and F. F. Poordad, “Cost-Efficacy Analysis of Peginterferon Alfa-2b Plus Ribavirin Compared with Peginterferon Alfa-2a Plus Ribavirin for the Treatment of Chronic Hepatitis C,” Journal of Managed Care Pharmacy, Vol. 11, No. 8, 2005, pp. 687-694.
[33] K. R. Reddy, M. L. Shiffman, T. R. Morgan, S. Zeuzem, S. Hadziyannis, F. M. Hamzeh, T. L. Wright and M. Fried, “Impact of Ribavirin Dose Reductions in Hepatitis C Virus Genotype 1 Patients Completing Peginterferon Alfa-2a/Ribavirin Treatment,” Clinical Gastroenterology and Hepatology, Vol. 5, No. 1, 2007, pp. 124-129.
http://dx.doi.org/10.1016/j.cgh.2006.10.008
[34] S. Zopf, C. Herold, E. G. Hahn and M. Ganslmayer, “Peginterferon Alfa-2a Relapse Rates Depend on Weight-Based Ribavirin Dosage in HCV-Infected Patients with Genotype 1: Results of a Retrospective Evaluation,” Scandinavian Journal of Gastroenterology, Vol. 44, No. 4, 2009, pp. 486-490.
http://dx.doi.org/10.1080/00365520802647400
[35] C. Dhalluin, A. Ross, W. Huber, P. Gerber, D. Brugger, B. Gsell and H. Senn, “Structural, Kinetic, and Thermodynamic Analysis of the Binding of the 40 kDa PEG-Interferon-α2a and Its Individual Positional Isomers to the Extracellular Domain of the Receptor IFNAR2,” Bioconjugate Chemistry, Vol. 16, No. 3, 2005, pp. 518-527.
http://dx.doi.org/10.1021/bc049780h
[36] M. Silva, J. Poo, F. Wagner, M. Jackson, D. Cutler, M. Grace, R. Bordens, C. Cullen, J. Harvey and M. Laughlin, “A Randomised Trial to Compare the Pharmacokinetic, Pharmacodynamic, and Antiviral Effects of Peginterferon Alfa-2b and Peginterferon Alfa-2a in Patients with Chronic Hepatitis C (COMPARE),” Journal of Hepatology, Vol. 45, No. 2, 2006, pp. 204-213.
http://dx.doi.org/10.1016/j.jhep.2006.03.008
[37] M. O. Silva, “Compare Trial: Updated Data,” Journal of Hepatology, Vol. 49, No. 2, 2008, pp. 288-289.
http://dx.doi.org/10.1016/j.jhep.2008.05.009
[38] C. Sarrazin, S. Susser, A. Doehring, C. M. Lange, T. Muller, C. Schlecker, E. Herrmann, J. Lötsch and T. Berg, “Importance of IL28B Gene Polymorphisms in Hepatitis C Virus Genotype 2 and 3 Infected Patients,” Journal of Hepatology, Vol. 54, No. 3, 2011, pp. 415-421.
http://dx.doi.org/10.1016/j.jhep.2010.07.041
[39] J. G. McHutchison, M. Manns, K. Patel, T. Poynard, K. L. Lindsay, C. Trepo, J. Dienstag, W. M. Lee, C. Mak, J. J. Garaud and J. K. Albrecht, “Adherence to Combination Therapy Enhances Sustained Response in Genotype-1-Infected Patients with Chronic Hepatitis C,” Gastroenterology, Vol. 123, No. 4, 2002, pp. 1061-1069.
http://dx.doi.org/10.1053/gast.2002.35950

  
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