Scientific journal
European Journal of Natural History
ISSN 2073-4972

THE USE OF INTERFERONS IN CHRONIC VIRAL LIVER DISEASES

Parakhonsky A.P., Tsyganok S.S.
The increased disease a chronic hepatitis and low efficiency of treatment causes necessity of profound their studying immunopathogenesis and development of new methods of therapy. The broad effects of intercellular actions of interferons (IFN) can be roughly divided into: a) antiviral, b) anticancer, c) immunomodulatory. IFN are not produced constantly, so that their concentration in normal tissues is minimal or undetectable. However, after stimulating factors, esp. infections, their level in tissues highly increases, as a result of the activation of immunocompetent cells; later IFN bind to their specific receptors.

The strongest antiviral action exerts IFN-α. It influences all the stages of viral replication, but most important is inhibition of the genome translation, what makes defective the synthesis of viral proteins (kinases phosphorylate). The second mechanism of translation inhibition is the induction of 2´5´-oligosynthetase which degrades viral RNA. Both mechanisms omit healthy cells in their inhibitory actions. Furthermore, antiviral effect is achieved also by the increased expression of histocompatibility antigens and stimulation of the immune response. Interferons are now produced in the recombinant form, what enhanced their broader use. They are offered for treatment of adult patients and children with a chronic hepatitis. However, IFN-α is most widely used for the treatment of chronic viral hepatitis B and C.

We report results of treatment of 184 children, mostly with chronic aggressive type B hepatitis, HBsAg and HBeAg positive. Treatment consisted of 3 weekly, doses of 3 MU recombinant IFN-a, mean: 4.51 MU/m2 for 16 weeks (ca. 3 months). In the evaluation one year post IFN: 12% of children proved to be complete responders [HBsAg(-), eAg(-)], 53% of children partial responders [HBsAg(+), but eAg(-)], and 35% - nonresponders [HBsAg(+), eAg(+)]. The treatment was quite well tolerated; but such side effects as fever, loss of appetite, headaches, muscle and joint aches were noted in over 10% of children. The reference (unrelated) group consisted of 77 children (53 boys and 24 girls). During the same period, 2.6% of them became complete responders, 22.1% - partial responders and 75.3% remained nonresponders.

Moreover, in part of the treated children (n-23) we have determined pretreatment prognostic factors, by measuring HBeAg, HBsAg and HBV-DNA quantitatively, in addition to ALT and clinical chemistry. We have found differences between arithmetic means of these parameters, but because of big range of results, the statistically significant differences were obtained only in relation to age of children and HBeAg concentrations. We have shown, that low initial level of HBeAg, HBsAg, low level of HBV-DNA, as well as relatively high ALT value, together with rather low age of children were connected with the good prognosis for response. With regard to chronic hepatitis C - female gender, lower level of HVC-RNA, and lower age, but elevated baseline ALT were associated with good prognosis for response to INF-α therapy.

However, monotherapy with INF-α would give sustained response (persistent normalization of transaminases and negative HCV-RNA) in only ca. 20% of patients after 2 years of follow-up. In adults, interferon combined with ribavirin may raise the effectiveness about 2 times. Our current project in children concentrates on the inhibition of metabolites of arachidonic acid formed during the INF therapy. These metabolites, including prostaglandins (PGE2) and tromboxanes could be suppressed by inhibiting cycloxygenase with indomethacin.

The article is admitted to the International Scientific Conference " Priorities of Science and Technology Development: Educational Technologies "; Greece (Athens - Argolida - Delphi - Meteora - Athens), 2007, March 23-30; came to the editorial office on 13.03.07