Cytogenetic methods for detection of oxidative stress and evaluation of antioxidant therapy in hepatitis C infection.

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.