Skip to main content
Top
Published in: Journal of Gastroenterology 9/2012

01-09-2012 | Original Article—Liver, Pancreas, and Biliary Tract

Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients

Authors: Shiho Miyase, Katsuki Haraoka, Yoshihiro Ouchida, Yuko Morishita, Shigetoshi Fujiyama

Published in: Journal of Gastroenterology | Issue 9/2012

Login to get access

Abstract

Background

Pegylated interferon (PegIFN) plus ribavirin is the standard therapy for patients with chronic hepatitis C genotype 1. Although several randomized clinical trials have compared PegIFNα-2a with PegIFNα-2b, these 2 regimens have not been directly compared in Asian patients. We, therefore, compared the safety and antiviral efficacy of these agents in Japanese patients.

Methods

A total of 201 PegIFN-naïve, chronic hepatitis C patients were randomly assigned to once-weekly PegIFNα-2a (180 μg) or PegIFNα-2b (60–150 μg) plus ribavirin. We compared the sustained virological response (SVR) rates between the 2 regimens and analyzed their effects in relation to baseline characteristics, including single nucleotide polymorphisms (SNPs) near the interleukin-28B (IL28B) gene (rs8099917).

Results

PegIFNα-2a was associated with a higher SVR rate than PegIFNα-2b (65.3 vs. 51.0%, P = 0.039). PegIFNα-2a and SNPs near IL28B independently predicted SVR (odds ratio 2.36; 95% confidence interval [CI] 1.19–15.50, and odds ratio 7.31; 95% CI 3.45–4.68, respectively) in logistic regression analysis. PegIFNα-2a was more effective than PegIFNα-2b (81.8 vs. 62.7%, P = 0.014) in IL28B TT genotype patients, despite similarly low SVR rates in patients with TG or GG genotypes (36.4 vs. 35.9%). Patients weighing <60 kg, women, and patients aged >60 years had significantly higher SVR rates with PegIFNα-2a than with PegIFNα-2b (63.9, 61.3, and 67.3% vs. 43.8, 43.3,and 39.2%, respectively).

Conclusions

PegIFNα-2a plus ribavirin resulted in higher SVR rates than PegIFNα-2b plus ribavirin in Japanese patients. PegIFNα-2a-based treatment should therefore be the preferred choice for women, older or low-weight patients, and those with the IL28B TT genotype.
Literature
1.
go back to reference World Health Organization. Global surveillance and control of hepatitis C. J Viral Hepat. 1999;6:35–47.CrossRef World Health Organization. Global surveillance and control of hepatitis C. J Viral Hepat. 1999;6:35–47.CrossRef
2.
go back to reference Izumi N, Nishiguchi S, Hino K, Suzuki F, Kumada H, Itoh Y, et al. Management of hepatitis C: report of the Consensus Meeting at the 45th Annual Meeting of the Japan Society of Hepatology. Hepatol Res. 2010;40:347–68.CrossRef Izumi N, Nishiguchi S, Hino K, Suzuki F, Kumada H, Itoh Y, et al. Management of hepatitis C: report of the Consensus Meeting at the 45th Annual Meeting of the Japan Society of Hepatology. Hepatol Res. 2010;40:347–68.CrossRef
3.
go back to reference Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Gonçales 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, Gonçales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347:975–82.PubMedCrossRef
4.
go back to reference Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355:2444–51.PubMedCrossRef Hoofnagle JH, Seeff LB. Peginterferon and ribavirin for chronic hepatitis C. N Engl J Med. 2006;355:2444–51.PubMedCrossRef
5.
go back to reference Yoshida H, Tateishi R, Arakawa Y, Sata M, Fujiyama S, Nishiguchi S, et al. Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C. Gut. 2004;53:425–30.PubMedCrossRef Yoshida H, Tateishi R, Arakawa Y, Sata M, Fujiyama S, Nishiguchi S, et al. Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C. Gut. 2004;53:425–30.PubMedCrossRef
6.
go back to reference 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
7.
go back to reference Rumi MG, Aghemo A, Prati GM, D’Ambrosio R, Donato MF, Soffredini R, et al. Randomized study of peginterferon-α2a plus ribavirin vs peginterferon-α2b plus ribavirin in chronic hepatitis C. Gastroenterology. 2010;138:108–15.PubMedCrossRef Rumi MG, Aghemo A, Prati GM, D’Ambrosio R, Donato MF, Soffredini R, et al. Randomized study of peginterferon-α2a plus ribavirin vs peginterferon-α2b plus ribavirin in chronic hepatitis C. Gastroenterology. 2010;138:108–15.PubMedCrossRef
8.
go back to reference Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology. 2010;138:116–22.PubMedCrossRef Ascione A, De Luca M, Tartaglione MT, Lampasi F, Di Costanzo GG, Lanza AG, et al. Peginterferon alfa-2a plus ribavirin is more effective than peginterferon alfa-2b plus ribavirin for treating chronic hepatitis C virus infection. Gastroenterology. 2010;138:116–22.PubMedCrossRef
9.
go back to reference Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.PubMedCrossRef Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–93.PubMedCrossRef
10.
go back to reference Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:462–8.CrossRef Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, et al. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Am J Physiol Endocrinol Metab. 2005;288:462–8.CrossRef
11.
go back to reference Ito K, Higami K, Masaki N, Sugiyama M, Mukaide M, Saito H, et al. The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B. J Clin Microbiol. 2011;49:1853–60.PubMedCrossRef Ito K, Higami K, Masaki N, Sugiyama M, Mukaide M, Saito H, et al. The rs8099917 polymorphism, when determined by a suitable genotyping method, is a better predictor for response to pegylated alpha interferon/ribavirin therapy in Japanese patients than other single nucleotide polymorphisms associated with interleukin-28B. J Clin Microbiol. 2011;49:1853–60.PubMedCrossRef
12.
go back to reference Ohnishi Y, Tanaka T, Ozaki K, Yamada R, Suzuki H, Nakamura Y. A high-throughput SNP typing system for genome-wide association studies. J Hum Genet. 2001;46:471–7.PubMedCrossRef Ohnishi Y, Tanaka T, Ozaki K, Yamada R, Suzuki H, Nakamura Y. A high-throughput SNP typing system for genome-wide association studies. J Hum Genet. 2001;46:471–7.PubMedCrossRef
13.
go back to reference Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials. Hepatology. 2010;51:1176–84.PubMedCrossRef Awad T, Thorlund K, Hauser G, Stimac D, Mabrouk M, Gluud C. Peginterferon alpha-2a is associated with higher sustained virological response than peginterferon alfa-2b in chronic hepatitis C: systematic review of randomized trials. Hepatology. 2010;51:1176–84.PubMedCrossRef
14.
go back to reference Oze T, Hiramatsu N, Yakushijin T, Kurokawa M, Igura T, Mochizuki K, et al. Pegylated interferon alpha-2b (Peg-IFN alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-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 alpha-2b) affects early virologic response dose-dependently in patients with chronic hepatitis C genotype 1 during treatment with Peg-IFN alpha-2b plus ribavirin. J Viral Hepat. 2009;16:578–85.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference Toyoda H, Kumada T. Pharmacotherapy of chronic hepatitis C virus infection—the IDEAL trial: ‘2b or not 2b (=2a), that is the question’. Expert Opin Pharmacother. 2009;10:2845–57.PubMedCrossRef Toyoda H, Kumada T. Pharmacotherapy of chronic hepatitis C virus infection—the IDEAL trial: ‘2b or not 2b (=2a), that is the question’. Expert Opin Pharmacother. 2009;10:2845–57.PubMedCrossRef
17.
go back to reference Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, et al. Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. J Med Virol. 2007;79:1686–95.PubMedCrossRef Akuta N, Suzuki F, Kawamura Y, Yatsuji H, Sezaki H, Suzuki Y, et al. Predictors of viral kinetics to peginterferon plus ribavirin combination therapy in Japanese patients infected with hepatitis C virus genotype 1b. J Med Virol. 2007;79:1686–95.PubMedCrossRef
18.
go back to reference Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, et al. Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. J Gastroenterol. 2010;45:656–65.PubMedCrossRef Nakagawa M, Sakamoto N, Ueyama M, Mogushi K, Nagaie S, Itsui Y, et al. Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection. J Gastroenterol. 2010;45:656–65.PubMedCrossRef
19.
go back to reference Fellay J, Thompson AJ, Ge D, Gumbs CE, Urban TJ, Shianna KV, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature. 2010;464:405–8.PubMedCrossRef Fellay J, Thompson AJ, Ge D, Gumbs CE, Urban TJ, Shianna KV, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature. 2010;464:405–8.PubMedCrossRef
20.
go back to reference El-Shamy A, Nagano-Fujii M, Sasase N, Imoto S, Kim SR, Hotta H. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology. 2008;48:38–47.PubMedCrossRef El-Shamy A, Nagano-Fujii M, Sasase N, Imoto S, Kim SR, Hotta H. Sequence variation in hepatitis C virus nonstructural protein 5A predicts clinical outcome of pegylated interferon/ribavirin combination therapy. Hepatology. 2008;48:38–47.PubMedCrossRef
21.
go back to reference 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
22.
go back to reference 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
23.
go back to reference Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.PubMedCrossRef Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401.PubMedCrossRef
24.
go back to reference 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
25.
go back to reference Melis R, Fauron C, McMillin G, Lyon E, Shirts B, Hubley LM, et al. Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response. J Mol Diagn. 2011;13:446–51.PubMedCrossRef Melis R, Fauron C, McMillin G, Lyon E, Shirts B, Hubley LM, et al. Simultaneous genotyping of rs12979860 and rs8099917 variants near the IL28B locus associated with HCV clearance and treatment response. J Mol Diagn. 2011;13:446–51.PubMedCrossRef
26.
go back to reference Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350:2265–71.PubMedCrossRef Muir AJ, Bornstein JD, Killenberg PG, Atlantic Coast Hepatitis Treatment Group. Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites. N Engl J Med. 2004;350:2265–71.PubMedCrossRef
27.
go back to reference Okanoue T, Itoh Y, Hashimoto H, Yasui K, Minami M, Takehara T, et al. Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study. J Gastroenterol. 2009;44:952–63.PubMedCrossRef Okanoue T, Itoh Y, Hashimoto H, Yasui K, Minami M, Takehara T, et al. Predictive values of amino acid sequences of the core and NS5A regions in antiviral therapy for hepatitis C: a Japanese multi-center study. J Gastroenterol. 2009;44:952–63.PubMedCrossRef
Metadata
Title
Randomized trial of peginterferon α-2a plus ribavirin versus peginterferon α-2b plus ribavirin for chronic hepatitis C in Japanese patients
Authors
Shiho Miyase
Katsuki Haraoka
Yoshihiro Ouchida
Yuko Morishita
Shigetoshi Fujiyama
Publication date
01-09-2012
Publisher
Springer Japan
Published in
Journal of Gastroenterology / Issue 9/2012
Print ISSN: 0944-1174
Electronic ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-012-0560-9

Other articles of this Issue 9/2012

Journal of Gastroenterology 9/2012 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.