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.
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 naïve patients were studied. Nine were treated with pegylated IFN alfa-2a (PEG-IFN alpha-2a) plus ribavirin and rofecoxib; nine were treated with PEG-IFN alpha-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 alpha-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 < 0.001). These data suggest that: (1) a COX II inhibition is associated with an increase in the platelet count despite a reduction in the TPO level; (2) human IL-8 and human IL-13 but not hs-P-selectin levels decline in those who experience an early virologic response.
George
Magdalene M
MM
Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Loyola University Medical Center, Stritch School of Medicine, 2160 South First Avenue, Maywood, IL 60153, USA.
Li
S David
SD
Mindikoglu
Ayse L
AL
Baluch
Mehdi H
MH
Dhillon
Sonu
S
Farr
Deborah
D
Van Thiel
David H
DH
D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D018793:Interleukin-13 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008565:Membrane Proteins; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004337:Drug Carriers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D018793:Interleukin-13; D016209:Interleukin-8; D008565:Membrane Proteins; D019007:P-Selectin; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C100416:peginterferon alfa-2a