Pretreatment expression of the perforin gene by circulating CD8(+) T lymphocytes predicts biochemical response to interferon-alpha in patients with chronic hepatitis C

It would be of great value to be able to predict, before the initiation of treatment, which patients with hepatitis C virus-induced chronic hepatitis will be cured by interferon-alpha (IFN-alpha), Competitive RT-PCR was used to evaluate spontaneous expression of the perforin gene, a marker of cytoto xic cell activation, by circulating mononuclear cells in 17 patients underg oing IFN-alpha treatment, IFN-alpha increased perforin gene expression (p < 0.003), but this was not correlated with outcome. In contrast, pretreatmen t perforin gene expression levels were higher in the 8 patients with a sust ained biochemical response after treatment than in the 9 non-responsive pat ients (p = 0.01). This factor predicted favorable clinical outcome with a s ensitivity of 75% and a specificity of 89%, Thus, pretreatment immunologica l status has a major influence on the ability of IFN-alpha to cure chronic hepatitis C, and the evaluation of perforin gene expression may help to sel ect patients that will benefit from IFN-alpha treatment.