Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results

Bruce R. Bacon, Mitchell L. Shiffman, Flavia Mendes, Reem Ghalib, Tarek Hassanein, Giuseppe Morelli, Shobha Joshi, Kenneth Rothstein, Paul Kwo, Norman Gitlin

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75 Scopus citations

Abstract

Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/ RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 μg/day and RBV, and 242 received CIFN 15 μg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 μg group and 10.7% (26/242) in the 15 μg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log10 decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 μg group and 23% (7/31) in the 15 μg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/ 192) in the 9 μg group and 13.1% (23/175) in the 15 μg group. In this same group of patients (F0-F3), if a >2-log10 decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 μg and 15 μg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated. Conclusion: Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.

Original languageEnglish (US)
Pages (from-to)1838-1846
Number of pages9
JournalHepatology
Volume49
Issue number6
DOIs
StatePublished - Jun 1 2009

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ASJC Scopus subject areas

  • Hepatology

Cite this

Bacon, B. R., Shiffman, M. L., Mendes, F., Ghalib, R., Hassanein, T., Morelli, G., Joshi, S., Rothstein, K., Kwo, P., & Gitlin, N. (2009). Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results. Hepatology, 49(6), 1838-1846. https://doi.org/10.1002/hep.22871