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Vol. 53, No. 3, 2010
Issue release date: April 2010
Intervirology 2010;53:188–192
(DOI:10.1159/000289343)

Extending Combination Therapy with Peginterferon plus Ribavirin for Genotype 2 Chronic Hepatitis C Virological Responders: A Pilot Study of 7 Cases

Akuta N.a · Suzuki F.a · Arase Y.a · Hirakawa M.a · Kawamura Y.a · Yatsuji H.a · Sezaki H.a · Suzuki Y.a · Hosaka T.a · Kobayashi M.a · Kobayashi M.b · Saitoh S.a · Ikeda K.a · Kumada H.a
aDepartment of Hepatology and bLiver Research Laboratory, Toranomon Hospital, Tokyo, Japan
email Corresponding Author

Abstract

Objective: In treatment-resistant patients with genotype 2 chronic hepatitis C the suitable treatment duration is still unclear. The aims were to investigate extending combination therapy with peginterferon plus ribavirin for genotype 2. Methods: 7 patients infected with genotype 2 at a high viral load and who did not achieve a sustained virological response (SVR) with the first course of 24-week IFN plus ribavirin were recruited into the study protocol with a total of 48 weeks of peginterferon plus ribavirin therapy. Results: SVR was achieved in 5 of 7 patients (71%). All 4 patients (100%) who were in relapse with the first course achieved SVR. Only 1 of 3 patients (33%) who had a non-virological response (NVR) with the first course achieved SVR. All 4 patients who had an early virological response (EVR) with the first course achieved EVR and SVR. Two of 3 patients who had no EVR with the first course also did not achieve EVR and SVR. One patient who had no EVR or a NVR during the first course achieved EVR and SVR with the second course. Conclusions: Our results suggest that extending combination therapy for genotype 2 chronic hepatitis C might be useful for patients who relapse following 24-week combination therapy.


 goto top of outline Key Words

  • Hepatitis C virus
  • Genotype 2
  • Interferon
  • Ribavirin
  • Combination therapy, extended
  • Early virological response

 goto top of outline Abstract

Objective: In treatment-resistant patients with genotype 2 chronic hepatitis C the suitable treatment duration is still unclear. The aims were to investigate extending combination therapy with peginterferon plus ribavirin for genotype 2. Methods: 7 patients infected with genotype 2 at a high viral load and who did not achieve a sustained virological response (SVR) with the first course of 24-week IFN plus ribavirin were recruited into the study protocol with a total of 48 weeks of peginterferon plus ribavirin therapy. Results: SVR was achieved in 5 of 7 patients (71%). All 4 patients (100%) who were in relapse with the first course achieved SVR. Only 1 of 3 patients (33%) who had a non-virological response (NVR) with the first course achieved SVR. All 4 patients who had an early virological response (EVR) with the first course achieved EVR and SVR. Two of 3 patients who had no EVR with the first course also did not achieve EVR and SVR. One patient who had no EVR or a NVR during the first course achieved EVR and SVR with the second course. Conclusions: Our results suggest that extending combination therapy for genotype 2 chronic hepatitis C might be useful for patients who relapse following 24-week combination therapy.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Simmonds P: Clinical relevance of hepatitis C virus genotypes. Gut 1997;40:291–293.
  2. Haydon GH, Jarvis LM, Blair CS, Simmonds P, Harrison DJ, Simpson KJ, Hayes PC: Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection. Gut 1998;42:570–575.
  3. Akuta N, Suzuki F, Tsubota A, Suzuki Y, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors. J Hepatol 2002;37:831–836.
  4. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling MH, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001;358:958–965.
  5. Fried MW, Shiffman ML, Reddy R, Smith C, Marinos G, Gonçales FL, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–982.
  6. Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A: Peginterferon alfa-2b and ribavirin for 12 versus 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005;352:2609–2617.
  7. Mangia A, Minerva N, Bacca D, Cozzolongo R, Agostinacchio E, Sogari F, Scotto G, Vinelli F, Ricci GL, Romano M, Carretta V, Petruzzellis D, Andriulli A: Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection. Hepatology 2009;49:358–363.
  8. von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S: Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology 2005;129:522–527.
  9. Fujiwara K, Yokosuka O, Komine F, Moriyama M, Kato N, Yoshida H, Tanaka N, Imazeki F, Shiratori Y, Arakawa Y, Omata M; Tokyo Hepatitis Network: Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1. Liver Int 2006;26:520–528.
  10. Akuta N, Suzuki F, Tsubota A, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype 2a low viral load and response to interferon monotherapy. J Med Virol 2003;69:376–383.
  11. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 2a high viral load and virological response to interferon-ribavirin combination therapy. Intervirology 2009;52:301–309.
  12. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–982.
  13. 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;38:645–652.
  14. Chayama K, Tsubota A, Arase Y, Saitoh S, Koida I, Ikeda K, Matsumoto T, Kobayashi M, Iwasaki S, Koyama S, Morinaga T, Kumada H: Genotypic subtyping of hepatitis C virus. J Gastroenterol Hepatol 1993;8:150–156.
  15. Desmet VJ, Gerber M, Hoofnagle JH, Manna M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.
  16. Buti M, Valdés A, Sánchez-Avila F, Esteban R, Lurie Y: Extending combination therapy with peginterferon alfa-2b plus ribavirin for genotype 1 chronic hepatitis C late responders: a report of 9 cases. Hepatology 2003;37:1226–1227.
  17. Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, Zeuzem S: Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 2006;130:1086–1097.
  18. Sánchez-Tapias JM, Diago M, Escartín P, Enríquez J, Romero-Gómez M, Bárcena R, Crespo J, Andrade R, Martínez-Bauer E, Pérez R, Testillano M, Planas R, Solá R, García-Bengoechea M, Garcia-Samaniego J, Muñoz-Sánchez M, Moreno-Otero R; TeraViC-4 Study Group: Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology 2006;131:451–460.
  19. Pearlman BL, Ehleben C, Saifee S: Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology 2007;46:1688–1694.
  20. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response. J Med Virol 2009;81:452–458.
  21. Nousbaum JB, Cadranel JF, Savary O, Legrand MC, Dumouchel P, Gouérou H: Sustained virological response after a short course of treatment with interferon and ribavirin in two chronic hepatitis C patients. J Hepatol 2003;39:655–656.
  22. Dalgard O, Bjøro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H: Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 2004;40:1260–1265.
  23. Nagase Y, Yotsuyanagi H, Okuse C, Yasuda K, Kato T, Koike K, Suzuki M, Nishioka K, Iino S, Itoh F: Effect of treatment with interferon alpha-2b and ribavirin in patients infected with genotype 2 hepatitis C virus. Hepatol Res 2008;38:252–258.
  24. Nomura H, Miyagi Y, Tanimoto H, Ishibashi H: Impact of early viral kinetics on pegylated interferon alpha 2b plus ribavirin therapy in Japanese patients with genotype 2 chronic hepatitis C. J Viral Hepat 2009;16:346–351.
  25. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, Atsumi H, Nakano S, Arakawa T: Eight-week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response. Liver Int 2009;29:120–125.
  26. Murakami T, Enomoto N, Kurosaki M, Izumi N, Marumo F, Sato C: Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection. Hepatology 1999;30:1045–1053.
  27. Akuta N, Suzuki F, Suzuki Y, Sezaki H, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kobayashi M, Kumada H: Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: virological features of IFN-resistant cases with hepatocyte steatosis. J Med Virol 2005;75:550–558.

 goto top of outline Author Contacts

Norio Akuta, MD
Department of Hepatology
Toranomon Hospital
2-2-2 Toranomon, Minato-ku, Tokyo 105-0001 (Japan)
Tel. +81 44 877 5111, Fax +81 44 860 1623, E-Mail akuta-gi@umin.ac.jp


 goto top of outline Article Information

Received: November 2, 2009
Accepted after revision: January 6, 2010
Published online: March 3, 2010
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 1, Number of References : 27


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 53, No. 3, Year 2010 (Cover Date: April 2010)

Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Objective: In treatment-resistant patients with genotype 2 chronic hepatitis C the suitable treatment duration is still unclear. The aims were to investigate extending combination therapy with peginterferon plus ribavirin for genotype 2. Methods: 7 patients infected with genotype 2 at a high viral load and who did not achieve a sustained virological response (SVR) with the first course of 24-week IFN plus ribavirin were recruited into the study protocol with a total of 48 weeks of peginterferon plus ribavirin therapy. Results: SVR was achieved in 5 of 7 patients (71%). All 4 patients (100%) who were in relapse with the first course achieved SVR. Only 1 of 3 patients (33%) who had a non-virological response (NVR) with the first course achieved SVR. All 4 patients who had an early virological response (EVR) with the first course achieved EVR and SVR. Two of 3 patients who had no EVR with the first course also did not achieve EVR and SVR. One patient who had no EVR or a NVR during the first course achieved EVR and SVR with the second course. Conclusions: Our results suggest that extending combination therapy for genotype 2 chronic hepatitis C might be useful for patients who relapse following 24-week combination therapy.



 goto top of outline Author Contacts

Norio Akuta, MD
Department of Hepatology
Toranomon Hospital
2-2-2 Toranomon, Minato-ku, Tokyo 105-0001 (Japan)
Tel. +81 44 877 5111, Fax +81 44 860 1623, E-Mail akuta-gi@umin.ac.jp


 goto top of outline Article Information

Received: November 2, 2009
Accepted after revision: January 6, 2010
Published online: March 3, 2010
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 1, Number of References : 27


 goto top of outline Publication Details

Intervirology (International Journal of Basic and Medical Virology)

Vol. 53, No. 3, Year 2010 (Cover Date: April 2010)

Journal Editor: Liebert U.G. (Leipzig)
ISSN: 0300-5526 (Print), eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Simmonds P: Clinical relevance of hepatitis C virus genotypes. Gut 1997;40:291–293.
  2. Haydon GH, Jarvis LM, Blair CS, Simmonds P, Harrison DJ, Simpson KJ, Hayes PC: Clinical significance of intrahepatic hepatitis C virus levels in patients with chronic HCV infection. Gut 1998;42:570–575.
  3. Akuta N, Suzuki F, Tsubota A, Suzuki Y, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Efficacy of interferon monotherapy to 394 consecutive naive cases infected with hepatitis C virus genotype 2a in Japan: therapy efficacy as consequence of tripartite interaction of viral, host and interferon treatment-related factors. J Hepatol 2002;37:831–836.
  4. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling MH, Albrecht JK: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomized trial. Lancet 2001;358:958–965.
  5. Fried MW, Shiffman ML, Reddy R, Smith C, Marinos G, Gonçales FL, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–982.
  6. Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A: Peginterferon alfa-2b and ribavirin for 12 versus 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005;352:2609–2617.
  7. Mangia A, Minerva N, Bacca D, Cozzolongo R, Agostinacchio E, Sogari F, Scotto G, Vinelli F, Ricci GL, Romano M, Carretta V, Petruzzellis D, Andriulli A: Determinants of relapse after a short (12 weeks) course of antiviral therapy and re-treatment efficacy of a prolonged course in patients with chronic hepatitis C virus genotype 2 or 3 infection. Hepatology 2009;49:358–363.
  8. von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Häussinger D, Herrmann E, Zeuzem S: Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology 2005;129:522–527.
  9. Fujiwara K, Yokosuka O, Komine F, Moriyama M, Kato N, Yoshida H, Tanaka N, Imazeki F, Shiratori Y, Arakawa Y, Omata M; Tokyo Hepatitis Network: Twenty-four weeks of interferon alpha-2b in combination with ribavirin for Japanese hepatitis C patients: sufficient treatment period for patients with genotype 2 but not for patients with genotype 1. Liver Int 2006;26:520–528.
  10. Akuta N, Suzuki F, Tsubota A, Suzuki Y, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Association of amino acid substitution pattern in nonstructural protein 5A of hepatitis C virus genotype 2a low viral load and response to interferon monotherapy. J Med Virol 2003;69:376–383.
  11. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: Association of amino acid substitution pattern in core protein of hepatitis C virus genotype 2a high viral load and virological response to interferon-ribavirin combination therapy. Intervirology 2009;52:301–309.
  12. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales FL Jr, Häussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J: Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975–982.
  13. 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;38:645–652.
  14. Chayama K, Tsubota A, Arase Y, Saitoh S, Koida I, Ikeda K, Matsumoto T, Kobayashi M, Iwasaki S, Koyama S, Morinaga T, Kumada H: Genotypic subtyping of hepatitis C virus. J Gastroenterol Hepatol 1993;8:150–156.
  15. Desmet VJ, Gerber M, Hoofnagle JH, Manna M, Scheuer PJ: Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513–1520.
  16. Buti M, Valdés A, Sánchez-Avila F, Esteban R, Lurie Y: Extending combination therapy with peginterferon alfa-2b plus ribavirin for genotype 1 chronic hepatitis C late responders: a report of 9 cases. Hepatology 2003;37:1226–1227.
  17. Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, Buggisch P, Goeser T, Rasenack J, Pape GR, Schmidt WE, Kallinowski B, Klinker H, Spengler U, Martus P, Alshuth U, Zeuzem S: Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology 2006;130:1086–1097.
  18. Sánchez-Tapias JM, Diago M, Escartín P, Enríquez J, Romero-Gómez M, Bárcena R, Crespo J, Andrade R, Martínez-Bauer E, Pérez R, Testillano M, Planas R, Solá R, García-Bengoechea M, Garcia-Samaniego J, Muñoz-Sánchez M, Moreno-Otero R; TeraViC-4 Study Group: Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology 2006;131:451–460.
  19. Pearlman BL, Ehleben C, Saifee S: Treatment extension to 72 weeks of peginterferon and ribavirin in hepatitis c genotype 1-infected slow responders. Hepatology 2007;46:1688–1694.
  20. Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, Hosaka T, Kobayashi M, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kumada H: A matched case-controlled study of 48 and 72 weeks of peginterferon plus ribavirin combination therapy in patients infected with HCV genotype 1b in Japan: amino acid substitutions in HCV core region as predictor of sustained virological response. J Med Virol 2009;81:452–458.
  21. Nousbaum JB, Cadranel JF, Savary O, Legrand MC, Dumouchel P, Gouérou H: Sustained virological response after a short course of treatment with interferon and ribavirin in two chronic hepatitis C patients. J Hepatol 2003;39:655–656.
  22. Dalgard O, Bjøro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H: Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 2004;40:1260–1265.
  23. Nagase Y, Yotsuyanagi H, Okuse C, Yasuda K, Kato T, Koike K, Suzuki M, Nishioka K, Iino S, Itoh F: Effect of treatment with interferon alpha-2b and ribavirin in patients infected with genotype 2 hepatitis C virus. Hepatol Res 2008;38:252–258.
  24. Nomura H, Miyagi Y, Tanimoto H, Ishibashi H: Impact of early viral kinetics on pegylated interferon alpha 2b plus ribavirin therapy in Japanese patients with genotype 2 chronic hepatitis C. J Viral Hepat 2009;16:346–351.
  25. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Kanamori A, Atsumi H, Nakano S, Arakawa T: Eight-week regimen of antiviral combination therapy with peginterferon and ribavirin for patients with chronic hepatitis C with hepatitis C virus genotype 2 and a rapid virological response. Liver Int 2009;29:120–125.
  26. Murakami T, Enomoto N, Kurosaki M, Izumi N, Marumo F, Sato C: Mutations in nonstructural protein 5A gene and response to interferon in hepatitis C virus genotype 2 infection. Hepatology 1999;30:1045–1053.
  27. Akuta N, Suzuki F, Suzuki Y, Sezaki H, Hosaka T, Someya T, Kobayashi M, Saitoh S, Arase Y, Ikeda K, Kobayashi M, Kumada H: Hepatocyte steatosis is an important predictor of response to interferon (IFN) monotherapy in Japanese patients infected with HCV genotype 2a: virological features of IFN-resistant cases with hepatocyte steatosis. J Med Virol 2005;75:550–558.