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To the Editor:

We read with great interest the article by Buti et al.1 about the optimum duration of treatment for genotype 1–infected slow responders in the SUCCESS trial; however, we disagree with the authors' conclusion that 48 weeks of therapy with peginterferon and ribavirin, instead of 72 weeks, should remain the standard of care.

Although the trial was multicenter, only 159 slow responders were generated from 133 centers, with an average of 1.2 patients enrolled per site; this weakened the study considerably. Moreover, it is not clear why patients' fibrosis and insulin resistance scores were not reported; disparate numbers of patients with these traits may have skewed response rates. Furthermore, because the authors excluded patients weighing more than 125 kg, the results cannot be extrapolated to these patients either; ironically, these patients are more likely to be slow responders because they are treatment-resistant.

We were likewise disappointed by author misstatements in the discussion. Regarding our randomized trial of slow responders, the authors stated that the majority of our patients were African American. Actually, the majority of our patients were Caucasian. Regarding Ferenci et al.'s trial of slow responders, the authors did not accept the subjects as true slow responders because some were aviremic between weeks 4 and 12. Actually, more than 100 true slow responders were separately analyzed [the sustained virological response (SVR) rates were 29% and 35% for 48 and 72 weeks of treatment, respectively].

It is surprising that a recent analysis from SUCCESS was not discussed: some of the same authors4 demonstrated that patients who achieved a 2- to 3-log drop in their hepatitis C virus RNA levels at 12 weeks benefited from therapy extension (the SVR rates were 47% in the 72-week arm and 25% in the 48-week arm). Sarrazin et al.5 presented an analysis from the individualized treatment strategy according to early viral genetics in hepatitis C virus type 1-infecte patients (INDIV-2 trial), in which slowly responding patients who became aviremic on treatment after week 12 had better SVR with 72 weeks of treatment versus 48 weeks. In fact, the extension strategy may work best if slowly responding patients are treated for a finite time after aviremia is achieved. In a randomized study of extended therapy from Japan,6 the authors determined that the optimal duration of treatment-induced viremia suppression for best effecting an SVR is 44 weeks. Finally, 72 weeks of therapy beat 48 weeks in slowly responding patients with a genotype 1b infection and especially in those with variants in the hepatitis C virus core region.7

Because the SUCCESS trial enrolled a paucity of patients per site, included no African American patients or patients weighing more than 125 kg, and did not report the numbers of patients with insulin resistance and advanced fibrosis, how could its sweeping conclusion be generalizable to all slowly responding patients? We do not believe that the SUCCESS trial has closed the door to therapy prolongation for slow responders and strongly disagree with the authors that the current American Association for the Study of Liver Diseases guidelines, which allow for treatment extension in slowly responding patients, require reevaluation.

References

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  • 1
    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: 1201-1207.
  • 2
    Pearlman BN, Ehleten C, Salfee S. Treatment extension to 72 weeks or pegintuferon and ribairin in hepatitis c genotypes type 1-fected slow responders. HEPATOLOGY 2007; 46: 16881694.
  • 3
    Ferenci P, Laferl H, Scherzer TM, et al. Peginterferon alfa-za/ribavirin for 48 or 72 weeks in hepatitis C genotypes 1 and 4 with slow virologic response. Gastroenkology 2010; 138: 503512.
  • 4
    Buti M, Morozov VG, Rafalskly VV, Wong F, Sumskiene J, Faruqi R, et al. Slow responders benefit from 72 weeks PEG/RBV–Predicting treatment outcome among slow responders: a retrospective analysis of the SUCCESS study [Abstract]. http://www.natap.org/2010/EASL/EASL_55.htm. Accessed August 2010.
  • 5
    Sarrazin C, Schwendy S, Moller B, Dikopoulos N, Buggisch P, Encke J, et al. Completely individualized treatment durations (24, 30, 36, 42, 48, 60 or 72 weeks) with peginterferon-alfa-2b and ribavirin in HCV genotype 1-infected patients [Abstract]. http://www.kenes.com/easl2010/orals/203.htm. Accessed August 2010.
  • 6
    Ide T, Hino T, Ogata K, Miyajima I, Kuwahara R, Kuhara K, et al. A randomized study of extended treatment with peginterferon alfa-2b plus ribavirin based on time to HCV RNA negative-status in patients with genotype 1b chronic hepatitis C. Am J Gastroenterol 2009; 104: 70-75.
  • 7
    Akuta N, Suzuki F, Hirakawa M, Kawamura Y, Yatsuji H, Sezaki H, et al. 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. J Med Virol 2009; 81: 452-458.

Brian L. Pearlman M.D., F.A.C.P.* † ‡, Carole Ehleben Ed.D*, * Center for Hepatitis C Atlanta Medical Center Atlanta, GA, † Medical College of Georgia Augusta, GA, ‡ Emory School of Medicine Atlanta, GA.