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...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 phaseⅡstudy. 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.Themolecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well tolerated.An early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over time.Conversely,ketoprofen plus PEG- IFN 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.展开更多
文摘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 phaseⅡstudy. 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.Themolecular study of IFN-dependent signal transduction was conducted in 9 patients from each group. RESULTS:The combination of ketoprofen and PEG- IFN with or without ribavirin was safe and well tolerated.An early activation of STAT1 was observed in ke-toprofen-treated patients,but this activation was less sustained over time.Conversely,ketoprofen plus PEG- IFN 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.
