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

• Published in: Hepatology (Baltimore, Md.) Vol. 49; no. 6; pp. 1838 - 1846
• Main Authors: Bacon, Bruce R., Shiffman, Mitchell L., Mendes, Flavia, Ghalib, Reem, Hassanein, Tarek, Morelli, Giuseppe, Joshi, Shobha, Rothstein, Kenneth, Kwo, Paul, Gitlin, Norman
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.06.2009; Wiley
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; Biological and medical sciences; Drug Administration Schedule; Drug Therapy, Combination; Female; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis C, Chronic - drug therapy; Human viral diseases; Humans; Infectious diseases; Interferon Type I - administration & dosage; Interferon-alpha - therapeutic use; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - therapeutic use; Recombinant Proteins; Retreatment; Ribavirin - administration & dosage; Treatment Failure; Viral diseases; Viral hepatitis; Infection; Interferon alfacon-1; Peptides; Viral disease; Cytokine; Gastroenterology; Nucleoside analog; Digestive diseases; Hepatic disease; Antiviral; Ribavirin; Viral hepatitis C
• ISSN: 0270-9139; 1527-3350; 1527-3350
• DOI: 10.1002/hep.22871

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. (HEPATOLOGY 2009.)