Correlation of interferon-induced expression of MxA mRNA in peripheral blood mononuclear cells with the response of patients with chronic active hepatitis C to IFN-alpha therapy

MxA, a protein with selective activity against certain viruses, is an accep ted specific indicator of type I interferon (IFN) activity, We have develop ed an internally controlled quantitative-competitive PCR to measure the amo unts of MxA mRNA expressed in peripheral blood mononuclear cells (PBMC), Th is assay is more sensitive, quantitative, and easily applied to serial clin ical samples than previously described methods, We have applied this assay retrospectively to 27 patients with chronic active hepatitis C given IFN-al pha 2. Most such patients gain no sustained benefit but nevertheless suffer from the side effects, expense, and inconvenience of the treatment. Fourte en of the 27 had been classified on clinical grounds as responders and 13 a s nonresponders at the end of a 6 month treatment period. We measured MxA m RNA in PBMC obtained before and after 8 weeks of IFN-alpha 2 treatment. All the patients expressed some level of mRNA before treatment began, and afte r 8 weeks of treatment, the level rose in 19, This increase was significant (p < 0.001) only in patients classified as responders. This strongly sugge sts that hepatitis C virus (HCV) patients who express increased amounts of MxA mRNA in their PBMC during IFN-alpha treatment are most likely to obtain long-term benefit. If this finding is confirmed in future prospective stud ies, it will provide an extremely important predictive marker for managing IFN-alpha therapy in patients with HCV.