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.
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.
Magdalene M
MM
George
S David
SD
Li
Ayse L
AL
Mindikoglu
Mehdi H
MH
Baluch
Sonu
S
Dhillon
Deborah
D
Farr
David H
DH
Van Thiel
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