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
T. Oze
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
These authors contributed equally to this work.
Search for more papers by this authorN. Hiramatsu
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
These authors contributed equally to this work.
Search for more papers by this authorT. Yakushijin
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorM. Kurokawa
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Igura
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Mochizuki
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Imanaka
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan
Search for more papers by this authorH. Hagiwara
Higashiosaka City Central Hospital, Higashiosaka, Osaka, Japan
Search for more papers by this authorE. Mita
National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan
Search for more papers by this authorY. Inui
Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
Search for more papers by this authorT. Hijioka
National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan
Search for more papers by this authorE. Hayashi
Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Hyogo, Japan
Search for more papers by this authorM. Kato
National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
Search for more papers by this authorY. Yoshida
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Tatsumi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Ohkawa
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorS. Kiso
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Kanto
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorA. Kasahara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Takehara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorN. Hayashi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Oze
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
These authors contributed equally to this work.
Search for more papers by this authorN. Hiramatsu
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
These authors contributed equally to this work.
Search for more papers by this authorT. Yakushijin
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorM. Kurokawa
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Igura
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Mochizuki
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Imanaka
Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Osaka, Japan
Search for more papers by this authorH. Hagiwara
Higashiosaka City Central Hospital, Higashiosaka, Osaka, Japan
Search for more papers by this authorE. Mita
National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan
Search for more papers by this authorY. Inui
Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, Hyogo, Japan
Search for more papers by this authorT. Hijioka
National Hospital Organization Osaka Minami Medical Center, Kawachinagano, Osaka, Japan
Search for more papers by this authorE. Hayashi
Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Itami, Hyogo, Japan
Search for more papers by this authorM. Kato
National Hospital Organization Minami Wakayama Medical Center, Tanabe, Wakayama, Japan
Search for more papers by this authorY. Yoshida
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Tatsumi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorK. Ohkawa
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorS. Kiso
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Kanto
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorA. Kasahara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorT. Takehara
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorN. Hayashi
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan
Search for more papers by this authorAbstract
Summary. Chronic hepatitis C (CH-C) genotype 1 patients who achieved early virologic response have a high probability of sustained virologic response (SVR) following pegylated interferon (Peg-IFN) plus ribavirin therapy. This study was conducted to evaluate how reducing drug doses affects complete early virologic response (c-EVR) defined as hepatitis C virus (HCV) RNA negativity at week 12. Nine hundred eighty-four patients with CH-C genotype 1 were enrolled. Drug doses were evaluated independently on a body weight base from doses actually taken. From multivariate analysis, the mean dose of Peg-IFN α-2b during the first 12 weeks was the independent factor for c-EVR (P = 0.02), not ribavirin. The c-EVR rate was 55% in patients receiving ≥1.2 μg/kg/week of Peg-IFN, and declined to 38% at 0.9–1.2 μg/kg/week, and 22% in patients given <0.9 μg/kg/week (P < 0.0001). Even with stratified analysis according to ribavirin dose, the dose-dependent effect of Peg-IFN on c-EVR was observed, and similar c-EVR rates were obtained if the dose categories of Peg-IFN were the same. Furthermore, the mean dose of Peg-IFN during the first 12 weeks affected HCV RNA negativity at week 24 (P < 0.0001) and SVR (P < 0.0001) in a dose-dependent manner. Our results suggest that Peg-IFN was dose-dependently correlated with c-EVR, independently of ribavirin dose. Thus, maintaining the Peg-IFN dose as high as possible during the first 12 weeks can yield HCV RNA negativity and higher c-EVR rates, leading to better SVR rates in patients with CH-C genotype 1.
References
- 1 Hayashi N, Takehara T. Antiviral therapy for chronic hepatitis C: past, present, and future. J Gastroenterol 2006; 41: 17–27.
- 2 Manns MP, McHutchison JG, Gordon SC 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: 958–965.
- 3 Fried MW, Shiffman ML, Reddy KR et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002; 347: 975–982.
- 4 Hadziyannis SJ, Sette H Jr, Morgan TR 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: 346–355.
- 5 Zeuzem S, Hultcrantz R, Bourliere M 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: 993–999.
- 6 Hiramatsu N, Hayashi N, Kasahara A et al. Improvement of liver fibrosis in chronic hepatitis C patients treated with natural interferon alpha. J Hepatol 1995; 22: 135–142.
- 7 Kasahara A, Hayashi N, Mochizuki K 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: 1394–1402.
- 8 Ikeda K, Saitoh S, Arase Y 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: 1124–1130.
- 9 Kasahara A, Tanaka H, Okanoue T 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 Hepatitis 2004; 11: 148–156.
- 10 Imai Y, Kasahara A, Tanaka H et al. Interferon therapy for aged patients with chronic hepatitis C: improved survival in patients exhibiting a biochemical response. J Gastroenterol 2004; 39: 1069–1077.
- 11 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.
- 12 McHutchison JG, Manns M, Patel K et al. Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 2002; 123: 1061–1069.
- 13 Shiffman ML, Ghany MG, Morgan TR et al. Impact of reducing peginterferon alfa-2a and ribavirin dose during retreatment in patients with chronic hepatitis C. Gastroenterology 2007; 132: 103–112.
- 14 Reddy KR, Shiffman ML, Morgan TR et al. Impact of ribavirin dose reductions in hepatitis C virus genotype 1 patients completing peginterferon alfa-2a/ribavirin treatment. Clin Gastroenterol Hepatol 2007; 5: 124–129.
- 15 Shiffman ML, Salvatore J, Hubbard S et al. Treatment of chronic hepatitis C virus genotype 1 with peginterferon, ribavirin, and epoetin alpha. Hepatology 2007; 46: 371–379.
- 16 Paterson DL, Swindells S, Mohr J et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133: 21–30.
- 17 Strader DB, Wright T, Thomas DL, Seeff LB. Diagnosis, management, and treatment of hepatitis C. Hepatology 2004; 39: 1147–1171.
- 18 Dienstag JL, McHutchison JG. American Gastroenterological Association medical position statement on the management of hepatitis C. Gastroenterology 2006; 130: 225–230.
- 19 Poynard T, Marcellin P, Lee SS 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 1998; 352: 1426–1432.
- 20 McHutchison JG, Gordon SC, Schiff ER et al. Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. Hepatitis Interventional Therapy Group. N Engl J Med 1998; 339: 1485–1492.
- 21 Davis GL, Esteban-Mur R, Rustgi V et al. Interferon alfa-2b alone or in combination with ribavirin for the treatment of relapse of chronic hepatitis C. International Hepatitis Interventional Therapy Group. N Engl J Med 1998; 339: 1493–1499.
- 22 Hiramatsu N, Kasahara A, Nakanishi F et al. The significance of interferon and ribavirin combination therapy followed by interferon monotherapy for patients with chronic hepatitis C in Japan. Hepatol Res 2004; 29: 142–147.
- 23 Bronowicki JP, Ouzan D, Asselah T et al. Effect of ribavirin in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2a plus ribavirin. Gastroenterology 2006; 131: 1040–1048.
- 24 Hiramatsu N, Oze T, Yakushijin T, et al. Ribavirin dose reduction raises relapse rate dose-dependently in genotype 1 patients with hepatitis C responding to pegylated interferon alfa-2b plus ribavirin. J Viral Hepat 2009; In press.
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