Abstract :
The plasma of patients with hepatitis C contains chromosome-damaging substances,
the so-called “clastogenic factors” (CFs), as this is the case for other chronic inflammatory
diseases and after radiation exposure. These endogenous clastogens, formed
as a consequence of increased superoxide production by inflammatory cells, can be
detected with cytogenetic methods, as they are used for exogenous clastogens. The
long-lived, autosustained DNA-damaging effects of CFs are risk factors for the development
of cancer and leukemia. In hepatitis C, the highest clastogenic scores has been
observed in patients with hepatocellular carcinoma. In agreement with the link to
inflammation, clastogenic score are correlated with necro-inflammatory scores in
liver biopsies. Antioxidant therapy with a powerful superoxide scavenger resulted in
normalization of clastogenic scores and significant decreases in aminotransferase levels,
but did not influence the virus load. Preliminary results of our study on a limited
number of patients suggest that pre-treatment with antioxidants may improve the
outcome of interferon/ribavirin treatment. A comparison of a three-month treatment
with either interferon alone or the antioxidant alone, yielded similar results for reduction
of ALT levels, but only complete normalization of clastogenic scores for the
antioxidant. Further studies have to be conducted to see whether a combination of
an antiviral agent with an appropriate antioxidant would allow to reduce interferon
and its side effects.Combination of antioxidants with IFN/RIBA was also reported by
other authors with discordant results. The CF-test can be useful in clinical trials for the
choice of the appropriate antioxidant.
