Treatment with ribavirin and interferon-alpha reduces interferon-gamma expression in patients with chronic hepatitis C.

Recent studies in vitro and in animals have suggested that ribavirin may potentiate the antihepatitis C virus (HCV) activity of interferon-alpha (IFN-alpha) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-gamma, which play a key role in the cellular immune response against HCV. To study the immune-modulatory mechanisms of ribavirin further, cytokine production by activated T cells and circulating cytokine levels were studied by FACS analysis and ELISA testing in 25 patients with chronic hepatitis C unresponsive to IFN-alpha, before and after treatment with either ribavirin plus IFN-alpha or IFN-alpha alone. After 16 weeks of treatment, both the expression of IFN-gamma by activated T cells and the blood levels of IFN-gamma, were significantly reduced with respect to pretreatment values in patients treated with ribavirin and IFN-alpha but not in those undergoing treatment with IFN-alpha alone. The expression of IFN-gamma was significantly lower in patients that gained normal ALT levels with respect to those that did not. No modification of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in either group of patients. In conclusion, the results of this study do not support up-modulation of IFN-gamma and IL-2 production as the mechanism by which ribavirin potentiates IFN-alpha anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN-gamma-driven T cell activation and liver damage.

Unfavourable effects of colchicine in combination with interferon-alpha in the treatment of chronic hepatitis C.

BACKGROUND: The prognosis of chronic hepatitis depends on the progression of hepatic fibrosis. AIM: To investigate whether the antifibrotic drug colchicine, in combination with interferon-alpha has a role in the treatment of chronic hepatitis C. METHODS: Sixty-five HCV-RNA positive patients with chronic hepatitis were randomized to receive interferon-alpha, 6 MU t.i.w. for 6 months followed by 3 MU t.i.w. for further 6 months, with or without the adjunct of colchicine, 1 mg o.d., 6 days a week, for 3 years. We report an interim analysis after the first 18 months. RESULTS: Thirty-four patients received interferon-alpha and 31 received interferon-alpha and colchicine. The two groups were comparable for baseline data, including HCV-RNA levels, genotypes and histological grading/staging. Drop-outs and side-effects were similar. The proportion of patients who achieved alanine transaminase normalization or undetectable HCV-RNA at month 6 was higher in the interferon-alpha (68% and 47%, respectively) than in the interferon-alpha plus colchicine group (32% and 23%, P=0.004 and P=0. 04, respectively). End-of-treatment biochemical and virological response occurred in 41% and 29% of the interferon-alpha and 19% and 10% of the combination group, respectively (P=0.05 and P=0.05). Sustained biochemical response occurred in 26% of the interferon-alpha and 6% of the interferon-alpha plus colchicine group (P=0.03), corresponding percentages of sustained HCV-RNA loss being 21% and 3% (P=0.04). CONCLUSIONS: The combination of colchicine and interferon-alpha worsens the effectiveness of interferon-alpha alone in HCV chronic hepatitis. These alarming findings prompted us to interrupt the trial at this stage.

Cholesterol levels in Italian school children: results of an opportunistic survey.

BACKGROUND AND AIMS: A high prevalence of elevated serum total cholesterol (TC) levels has been described among Italian children. Universal screenings for TC have been suggested, though present recommendations are in favour of more selective and opportunistic surveys. Aim of the study was to assess TC distribution among 13-year-old schoolchildren in Central Italy. Further aim was to evaluate the indications for universal, selective or opportunistic screenings for TC. METHODS AND RESULTS: Children were examined opportunistically within a permanent screening programme for Mediterranean anemia carried out in the Lazio Region. TC was measured by dry chemistry in 3734 boys and 3644 girls aged 13 years from 77 schools in 37 municipalities. Results were grouped for 8 geographically and demographically similar areas. Mean TC was 137.6 mg/dl in boys and 144.3 mg/dl in girls. Desirable levels (< 170 mg/dl) were observed in about 90% of the children and fewer than 2% displayed levels indicative of genetic hypercholesterolemia (> 200 mg/dl). However, in two areas mainly populated by descendants from Northern Italy mean TC was remarkably high (158.7 and 152.2 mg/dl in boys and 164.5 and 160.0 in girls) and the percentage with desirable levels dropped to 68.6% and 74.7%. CONCLUSIONS: Our results show average good TC levels among Italian schoolchildren in Central Italy. This is probably due to their traditional Mediterranean diet. It can thus be suggested that only selective and/or opportunistic screenings for TC are indicated. However, in some areas where fewer children have desirable levels and almost 30% require dietary education, large-scale screenings are highly recommended.