Skip to main content
Erschienen in: Journal of Gastroenterology 7/2011

01.07.2011 | Original Article—Liver, Pancreas, and Biliary Tract

The efficacy of extended treatment with pegylated interferon plus ribavirin in patients with HCV genotype 1 and slow virologic response in Japan

verfasst von: Tsugiko Oze, Naoki Hiramatsu, Takayuki Yakushijin, Kiyoshi Mochizuki, Kazuho Imanaka, Akira Yamada, Masahide Oshita, Akira Kaneko, Hideki Hagiwara, Eiji Mita, Toshifumi Ito, Toshihiko Nagase, Yoshiaki Inui, Taizo Hijioka, Shinji Tamura, Harumasa Yoshihara, Eijiro Hayashi, Yasuharu Imai, Michio Kato, Atsushi Hosui, Takuya Miyagi, Yuichi Yoshida, Hisashi Ishida, Tomohide Tatsumi, Shinichi Kiso, Tatsuya Kanto, Akinori Kasahara, Tetsuo Takehara, Norio Hayashi

Erschienen in: Journal of Gastroenterology | Ausgabe 7/2011

Einloggen, um Zugang zu erhalten

Abstract

Background

Which patients with hepatitis C virus (HCV) genotype 1 can benefit from extended treatment with pegylated interferon (Peg-IFN) plus ribavirin is unknown, although the overall sustained virologic response (SVR) rate has been shown to improve in patients with a late virologic response (LVR), defined as detectable serum HCV RNA at week 12 and undetectable at week 24.

Methods

Among 1163 chronic hepatitis C patients with genotype 1 treated with Peg-IFN plus ribavirin combination therapy, 213 patients with an LVR were examined in this study. In addition, we selected 81 patients of matched sex and age from each of the 48- and 72-week treatment groups, using the propensity score, to compare the efficacy of the two treatment durations.

Results

With 72-week treatment, the timing of HCV RNA disappearance and the hemoglobin level at baseline showed a strong correlation with the SVR on multivariate analysis. Earlier HCV RNA disappearance was associated with a better SVR rate, regardless of the ribavirin dose (HCV RNA disappearance at week 16, 74%; at week 20, 52%; and at week 24, 31%, p = 0.01). The SVR rate with 72-week treatment was higher than that with 48-week treatment, irrespective of age, sex, or the platelet value, and, especially in aged patients (≥65 years old), the SVR rate increased markedly with 72-week treatment (48 weeks, 25% vs. 72 weeks, 56%; p < 0.05).

Conclusions

An earlier response predicts a higher SVR rate in patients with an LVR given 72-week treatment. Extended treatment with Peg-IFN plus ribavirin for patients with an LVR improved the treatment efficacy, even for aged patients.
Literatur
1.
Zurück zum Zitat Poynarl T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–32.CrossRef Poynarl T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet. 1997;349:825–32.CrossRef
2.
Zurück zum Zitat Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990;12:671–5.PubMedCrossRef Kiyosawa K, Sodeyama T, Tanaka E, Gibo Y, Yoshizawa K, Nakano Y, et al. Interrelationship of blood transfusion, non-A, non-B hepatitis and hepatocellular carcinoma: analysis by detection of antibody to hepatitis C virus. Hepatology. 1990;12:671–5.PubMedCrossRef
3.
Zurück zum Zitat Hiramatsu N, Hayashi N, Kasahara A, Hagiwara H, Takehara T, Haruna Y, et al. Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol. 1995;22:135–42.PubMedCrossRef Hiramatsu N, Hayashi N, Kasahara A, Hagiwara H, Takehara T, Haruna Y, et al. Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol. 1995;22:135–42.PubMedCrossRef
4.
Zurück zum Zitat Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology. 1998;27:1394–402.PubMedCrossRef Kasahara A, Hayashi N, Mochizuki K, Takayanagi M, Yoshioka K, Kakumu S, et al. Risk factors for hepatocellular carcinoma and its incidence after interferon treatment in patients with chronic hepatitis C. Osaka Liver Disease Study Group. Hepatology. 1998;27:1394–402.PubMedCrossRef
5.
Zurück zum Zitat Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med. 1999;131:174–81.PubMed Yoshida H, Shiratori Y, Moriyama M, Arakawa Y, Ide T, Sata M, et al. Interferon therapy reduces the risk for hepatocellular carcinoma: national surveillance program of cirrhotic and noncirrhotic patients with chronic hepatitis C in Japan. Ann Intern Med. 1999;131:174–81.PubMed
6.
Zurück zum Zitat Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1, 643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–30.PubMedCrossRef Ikeda K, Saitoh S, Arase Y, Chayama K, Suzuki Y, Kobayashi M, et al. Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1, 643 patients using statistical bias correction with proportional hazard analysis. Hepatology. 1999;29:1124–30.PubMedCrossRef
7.
Zurück zum Zitat Kurokawa M, Hiramatsu N, Oze T, Mochizuki K, Yakushijin T, Kurashige N, et al. Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma with chronic hepatitis. Hepatol Res. 2009;39:432–8.PubMedCrossRef Kurokawa M, Hiramatsu N, Oze T, Mochizuki K, Yakushijin T, Kurashige N, et al. Effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma with chronic hepatitis. Hepatol Res. 2009;39:432–8.PubMedCrossRef
8.
Zurück zum Zitat Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshida K, et al. Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death. J Viral Hepat. 2004;11:148–56.PubMedCrossRef Kasahara A, Tanaka H, Okanoue T, Imai Y, Tsubouchi H, Yoshida K, et al. Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death. J Viral Hepat. 2004;11:148–56.PubMedCrossRef
9.
Zurück zum Zitat Imai Y, Kasahara A, Tanaka H, Okanoue T, Hiramatsu N, Tsubouchi H, et al. Interferon therapy for aged patients with chronic hepatitis C: improved survival in patients exhibiting a biochemical response. J Gastroenterol. 2004;39:1069–77.PubMedCrossRef Imai Y, Kasahara A, Tanaka H, Okanoue T, Hiramatsu N, Tsubouchi H, et al. Interferon therapy for aged patients with chronic hepatitis C: improved survival in patients exhibiting a biochemical response. J Gastroenterol. 2004;39:1069–77.PubMedCrossRef
10.
Zurück zum Zitat Hayashi N, Takehara T. Antiviral therapy for chronic hepatitis C: past, present, and future. J Gastroenterol. 2006;41:17–27.PubMedCrossRef Hayashi N, Takehara T. Antiviral therapy for chronic hepatitis C: past, present, and future. J Gastroenterol. 2006;41:17–27.PubMedCrossRef
11.
Zurück zum Zitat Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–74.PubMedCrossRef Ghany MG, Strader DB, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C: an update. Hepatology. 2009;49:1335–74.PubMedCrossRef
12.
Zurück zum Zitat Manns MP, McHutchison JG, 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.PubMedCrossRef Manns MP, McHutchison JG, 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.PubMedCrossRef
13.
Zurück zum Zitat 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.PubMedCrossRef 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.PubMedCrossRef
14.
Zurück zum Zitat 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.PubMed 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.PubMed
15.
Zurück zum Zitat Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004;40:993–9.PubMedCrossRef Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004;40:993–9.PubMedCrossRef
16.
Zurück zum Zitat McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580–93.PubMedCrossRef McHutchison JG, Lawitz EJ, Shiffman ML, Muir AJ, Galler GW, McCone J, et al. Peginterferon alfa-2b or alfa-2a with ribavirin for treatment of hepatitis C infection. N Engl J Med. 2009;361:580–93.PubMedCrossRef
17.
Zurück zum Zitat Oze T, Hiramatsu N, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Pegylated interferon alpha-2b (Peg-IFN α-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN α-2b plus ribavirin. J Viral Hepat. 2009;16:578–85.PubMedCrossRef Oze T, Hiramatsu N, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Pegylated interferon alpha-2b (Peg-IFN α-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN α-2b plus ribavirin. J Viral Hepat. 2009;16:578–85.PubMedCrossRef
18.
Zurück zum Zitat Hiramatsu N, Oze T, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin. J Viral Hepat. 2009;16:586–94.PubMedCrossRef Hiramatsu N, Oze T, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alpha-2b plus ribavirin. J Viral Hepat. 2009;16:586–94.PubMedCrossRef
19.
Zurück zum Zitat Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130:1086–97.PubMedCrossRef Berg T, von Wagner M, Nasser S, Sarrazin C, Heintges T, Gerlach T, et al. Extended treatment duration for hepatitis C virus type 1: comparing 48 versus 72 weeks of peginterferon-alfa-2a plus ribavirin. Gastroenterology. 2006;130:1086–97.PubMedCrossRef
20.
Zurück zum Zitat 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;46:1688–94.PubMedCrossRef 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;46:1688–94.PubMedCrossRef
21.
Zurück zum Zitat Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology. 2008;47:43–50.PubMedCrossRef Mangia A, Minerva N, Bacca D, Cozzolongo R, Ricci GL, Carretta V, et al. Individualized treatment duration for hepatitis C genotype 1 patients: a randomized controlled trial. Hepatology. 2008;47:43–50.PubMedCrossRef
22.
Zurück zum Zitat Ferenci P, Laferl H, Scherzer TM, Maieron A, Hofer H, Stauber R, et al. Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response. Gastroenterology. 2010;138:503–12.PubMedCrossRef Ferenci P, Laferl H, Scherzer TM, Maieron A, Hofer H, Stauber R, et al. Peginterferon alfa-2a/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 patients with slow virologic response. Gastroenterology. 2010;138:503–12.PubMedCrossRef
23.
Zurück zum Zitat Sanchez-Tapias JM, Diago M, Escartin P, Enriquez J, Romero-Gomez M, Barcena R, et al. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology. 2006;131:451–60.PubMedCrossRef Sanchez-Tapias JM, Diago M, Escartin P, Enriquez J, Romero-Gomez M, Barcena R, et al. Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment. Gastroenterology. 2006;131:451–60.PubMedCrossRef
24.
Zurück zum Zitat Buti M, Lurie Y, Zakharova NG, Blokhina NP, Horban A, Teuber G, et al. Randomized trial of peginterferon alfa-2b and ribavirin for 48 or 72 weeks in patients with hepatitis C virus genotype 1 and slow virologic response. Hepatology. 2010;52:1201–7.PubMedCrossRef Buti M, Lurie Y, Zakharova NG, Blokhina NP, Horban A, Teuber G, et al. Randomized trial of peginterferon alfa-2b and ribavirin for 48 or 72 weeks in patients with hepatitis C virus genotype 1 and slow virologic response. Hepatology. 2010;52:1201–7.PubMedCrossRef
25.
Zurück zum Zitat Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, et al. Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy. J Hepatol. 2011;54:604–11. Oze T, Hiramatsu N, Yakushijin T, Mochizuki K, Oshita M, Hagiwara H, et al. Indications and limitations for aged patients with chronic hepatitis C in pegylated interferon alfa-2b plus ribavirin combination therapy. J Hepatol. 2011;54:604–11.
26.
Zurück zum Zitat Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.PubMedCrossRef Thomas DL, Thio CL, Martin MP, Qi Y, Ge D, O’Huigin C, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature. 2009;461:798–801.PubMedCrossRef
27.
Zurück zum Zitat Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–4.PubMedCrossRef Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41:1100–4.PubMedCrossRef
28.
Zurück zum Zitat Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–9.PubMedCrossRef Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–9.PubMedCrossRef
29.
Zurück zum Zitat Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in Hepatitis C virus-1 patients. Gastroenterology. 2010;139:120–9.PubMedCrossRef Thompson AJ, Muir AJ, Sulkowski MS, Ge D, Fellay J, Shianna KV, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest pretreatment predictor of sustained virologic response in Hepatitis C virus-1 patients. Gastroenterology. 2010;139:120–9.PubMedCrossRef
Metadaten
Titel
The efficacy of extended treatment with pegylated interferon plus ribavirin in patients with HCV genotype 1 and slow virologic response in Japan
verfasst von
Tsugiko Oze
Naoki Hiramatsu
Takayuki Yakushijin
Kiyoshi Mochizuki
Kazuho Imanaka
Akira Yamada
Masahide Oshita
Akira Kaneko
Hideki Hagiwara
Eiji Mita
Toshifumi Ito
Toshihiko Nagase
Yoshiaki Inui
Taizo Hijioka
Shinji Tamura
Harumasa Yoshihara
Eijiro Hayashi
Yasuharu Imai
Michio Kato
Atsushi Hosui
Takuya Miyagi
Yuichi Yoshida
Hisashi Ishida
Tomohide Tatsumi
Shinichi Kiso
Tatsuya Kanto
Akinori Kasahara
Tetsuo Takehara
Norio Hayashi
Publikationsdatum
01.07.2011
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 7/2011
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-011-0403-0

Weitere Artikel der Ausgabe 7/2011

Journal of Gastroenterology 7/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.