| Abstract: | AIM: To evaluate the safety of adding ketoprofen to pegylated-interferon ( PEG-IFN) with or without ribavirin and the effect on viral kinetics, STAT1 activity and expression of 2'-5'-oligoadenylate synthetase (2'-5'OAS) in genotype 1 chronic hepatitis C in a phase Ⅱ study. METHODS: Forty-five patients were studied: fifteen were randomized to PEG-IFN plus ribavirin (PR), 16 to PEGIFN plus ketoprofen and 14 to PR and ketoprofen. The molecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS: The combination of ketoprofen and PEGIFN with or without ribavirin was safe and well tolerated. An early activation of STAT1 was observed in ketoprofen- treated patients, but this activation was less sustained over time. Conversely, ketoprofen plus PEGIFN and ribavirin induced an early and sustained increase of 2'-5'OAS transcription starting 24 h after the first dose until the 36th wk. These data are consistent with the clinical results, showing a better sustained virological response and a lower relapse rate in patients receiving ketoprofen plus PEG-IFN and ribavirin. CONCLUSION: The addition of ketoprofen to the standard therapy of chronic hepatitis C should be explored in larger randomized clinical studies. |
