Platelet sparing effect of COX II inhibition used with pegylated interferon alfa-2a for the treatment of chronic hepatitis C: a short term pilot study

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2004-09, Vol.27 (6), p.159-165
• Main Authors: George, Magdalene M, Li, S.David, Mindikoglu, Ayse L, Baluch, Mehdi H, Dhillon, Sonu, Farr, Deborah, Van Thiel, David H
• Format: Article
• Language: English
• Subjects: Antiviral Agents - therapeutic use; Biomarkers; Blood Platelets - metabolism; COX II; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - therapeutic use; Drug Carriers; Drug Therapy, Combination; Hepacivirus - genetics; Hepacivirus - metabolism; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - immunology; Humans; Interferon; Interferon-alpha - therapeutic use; Interleukin-13 - blood; Interleukin-8 - blood; Membrane Proteins; Middle Aged; P-Selectin - blood; Platelets; Polyethylene Glycols - therapeutic use; Prostaglandin-Endoperoxide Synthases - metabolism; Recombinant Proteins; Ribavirin - therapeutic use; Viral Load
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2004.05.005

The role of a cyclooxygenase (COX) II inhibitor in reducing microvascular inflammation and the platelet count associated with interferon (IFN) plus ribavirin therapy of chronic hepatitis C (HCV) was assessed. Three plasma mediators (biomarkers) associated with platelet activation, inflammation and fibrosis were measured. Eighteen IFN naı̈ve patients were studied. Nine were treated with pegylated IFN alfa-2a (PEG-IFN α-2a) plus ribavirin and rofecoxib; nine were treated with PEG-IFN α-2a plus ribavirin. A complete blood count, liver panel and HCV-RNA were assayed weekly. Human soluble P-selectin (hs-P-selectin), human interleukin-8 (IL-8), human interleukin-13 (IL-13) and human thrombopoietin (TPO) were assayed at 4 week intervals. The COX II inhibitor reduced the platelet reduction experienced with PEG-IFN α-2a treatment of HCV despite a reduction in the plasma TPO level. Hs-P-selectin was increased in both groups. In contrast, human IL-8 levels declined to undetectable levels in virologic responders. Similarly, human IL-13 levels declined with therapy ( P