Treatment of chronic virus hepatitis with acetylsalicylic acid
Heinrich, D.; Maier, K.P.
Schweizerische Medizinische Wochenschrift 125(15): 755-757
1995
ISSN/ISBN: 0036-7672 PMID: 7740291 Document Number: 454609
The treatment of chronic hepatitis B and C with recombinant interferon (IFN) has only poor durable response rates. In the past only the lack of any prior effective therapy regimen could justify the use of this expensive agent. Dose escalating or prolonged treatment courses did not enhance the rate of sustained remissions. Pre- or cotreatment with antiviral (e.g. acyclovir, ribavirin, isoprenosin) or immunomodulating (e.g. prednisone, gamma IFN) drugs have not influenced the resistance to exogenous IFN of many patients. The mechanisms underlying resistance to this drug remain unknown. Some hypotheses focus on IFN antibodies, down regulation of IFN receptors or defects in the postreceptor response of cells to IFN. In 1991 Hannigan and Williams (Science 1991; 251: 204-207) described a synergistic signal transduction effect in human fibroblasts after exposure to IFN. Arachidonic acid (AA) activation from membrane phospholipid pools is common to many receptors and can be followed by metabolization of AA by cyclooxygenase to prostanoids, thromboxanes and eicosanoids and by lipoxygenase to leukotrienes; inhibition of these AA oxidation pathways by addition of inhibitors of these enzymes (e.g. indomethacin) resulted in marked amplification of the IFN signal, possibly by using the epoxygenase enzyme family as an alternative pathway. Our data are taken from the pretreatment part of a current study for evaluation of pre- and combination treatment with acetylsalicylic acid (ASA) as cyclooxygenase inhibitor and IFN in chronic hepatitis C. 27 patients with histologically proven chronic active hepatitis C were divided into two groups. Group A (16 patients,) were treated with a daily dose of 100 mg ASA orally, and the 11 patients in group B served as untreated controls. After 6 months of ASA monotherapy there was no improvement of hepatitis activity of the treatment group compared with the controls. Completion of our study will show whether patients pre- or cotreated with ASA and IFN have a better response rate and long term efficacy of therapy.