To the Editor:

Recently, Awad et al.1 presented a meta-analysis comparing peginterferon alfa-2a and peginterferon alfa-2b for the treatment of hepatitis C virus (HCV) infection. The authors conclude: “Current evidence suggests that peginterferon alpha-2a is significantly superior to peginterferon alfa-2b regarding benefits (SVR, which is clearance of the virus from the blood)”. After a careful revision of the article by Awad et al. and the original articles included in the meta-analysis, the conclusion they reach must be interpreted with caution. A main principle of meta-analysis deals with the homogeneity of the trials that will be analyzed together, in both aspects: population under study and methodological issues.2, 3 In addition, the quality of individual trials is important. However, these principles are not completely satisfied in the work of Awad et al.:

  • 1
    Two of the studies cited in Awad et al. (Sinha et al.4 and Kolakowska et al.5) were published as abstracts, without peer review.
  • 2
    Three of the articles used a stratified randomization. Two of them (Ascione et al.6 and Rumi et al.7) used a stratified randomization by genotype, and in the study by McHutchison et al.8, randomization was stratified by level of HCV and race.
  • 3
    Whereas most of the trials included treatment-naive patients, Laguno et al.9 worked with patients coinfected with human immunodeficiency virus and Scotto et al.10 included patients without response to previous treatment.
  • 4
    McHutchison included different races, and although five trials included patients infected with genotype 1 to 4, two trials included patients with genotype 1 (McHutchison et al.8 and Yenice et al.11), and Kolakowska et al. included only patients with genotype 3.
  • 5
    In the meta-analysis, 1016 patients with a lower dose of peginterferon alpha-2b were included.

Simultaneously, Alavian et al.12 presented a very similar article: “The Comparative Efficacy and Safety of Peginterferon Alpha-2a vs. 2b for the Treatment of Chronic HCV Infection: A Meta-Analysis.” Alavian et al. analyzed only five of the eight trials used by Awad et al. Alavian et al. reach nearly the same conclusion, but at the same time stated “A longer duration of maximum serum concentration compared with PEG-IFN-α2b (168 versus 48-72 hours) yields greater SVR and higher neutropenia in PEG-IFN-α2a recipients.” Both authors1, 12 mentioned some awareness about the quality of the meta-analysis and the studies included in it. We think that conclusion must be interpreted both in light of the included trials and considering the effects of other factors, such as baseline HCV level, sex, race, and genotype. We strongly believe more research is needed before it is concluded one peginterferon is better than the other.


  1. Top of page
  • 1
    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: 1176-1184.
  • 2
    Leandro G. Meta-Analysis in Medical Research: The Handbook for the Understanding and Practice of Meta-Analysis. Oxford, UK: Blackwell Publishing Ltd.; 2005.
  • 3
    Kulinskaya E, Morgenthaler S, Staudte RG. Meta Analysis: A Guide to Calibrating and Combining Statistical Evidence. Chichester, UK: John Wiley & Sons Ltd.; 2008.
  • 4
    Sinha S, Gulur P, Patel V, Hage-Nassar G, Tenner S. A randomized prospective clinical trial comparing pegylated interferon alpha 2a/ribavirin versus pegylated interferon alpha 2b/ribavirin in the treatment of chronic hepatitis C [Abstract]. Am J Gastroenterol 2004; 99: 237.
  • 5
    Kolakowska A, Berok H, Wasilewski M, Horbon A. Relevance between fibrosis and response to treatment with peginterferon alf2 vs alfa2b with ribavirin in chronic hepatitis C genotype 3 patients. Randomized open label study [Abstract]. HEPATOLOGY 2008; 48: 1278.
  • 6
    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: 116-122.
  • 7
    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: 108-115.
  • 8
    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: 580-593.
  • 9
    Laguno M, Cifuentes C, Murillas J, Veloso S, Larrousse M, Payeras A, et al. 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 2009; 49: 22-31.
  • 10
    Scotto G, Fazio V, Fornabaio C, Tartaglia A, Di Tullio R, Saracino A, et al. Peg-interferon alpha-2a versus peg-interferon alpha-2b in nonresponders with HCV active chronic hepatitis: a pilot study. J Interferon Cytokine Res 2008; 28: 623-630.
  • 11
    Yenice N, Mehtap O, Gumrah M, Arican N. The efficacy of pegylated interferon alpha 2a or 2b plus ribavirin in chronic hepatitis C patients. Turk J Gastroenterol 2006; 17: 94-98.
  • 12
    Alavian SM, Behnava B, Tabatabaei SV. The comparative efficacy and safety of peginterferon alpha-2a vs. 2b for the treatment of chronic HCV infection: a meta-analysis. Hepat Monthly 2010; 10: 121-131.

David Kershenobich M.D., Ph.D.*, Linda Muñoz†, René Malé‡, Jesús Gaytan§, Francisco Sánchez¶, * Laboratorio de Hígado, Páncreas y Motilidad, Departamento de Medicina Experimental, Facultad de Medicina de la UNAM, Hospital General de México, México DF, México, † Unidad de Hígado, Departamento de Medicina Interna, Hospital Universitario “Dr. José E. González” Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México, ‡ Centro de Enfermedades Digestivas y Hepáticas SC, Instituto de Salud Digestiva y Hepáticas SC, Guadalajara, Jalisco, México, § Hospital de Infectología. Centro Médico Nacional “La Raza”. Instituto Mexicano del Seguro Social, México DF, México, ¶ Departamento de Gastroenterología. Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán,” México DF, México.