Moreover, the IFNa-induced reduction of thymic function and its probable consequences on naïve T-cell diversity may contribute to the higher infectious risk associated with IFNa therapy, in particular observed in older patients [15, 16, 44] . There are multiple sources for circulating IL-7 during viral infections including lymphoid organs, epithelial cells and recently the liver was identified as a major source of IL-7. Moreover, increased plasma IL-7 levels can also be observed during viral infection in non-lymphopenic individuals ( [33] and unpublished data), suggesting a role in the development of immune responses. Indeed, this cytokine participates to T-cell homing in various lymphoid and non-lymphoid tissues through stimulation of local chemokine productions [45] . Increased IL-7 plasma levels in lymphopenic individuals is likely due to reduced consumption [46] yet augmented production to counteract lymphopenia cannot be excluded [33] . The recent identification of the liver as an IL-7 producing tissue upon TLR stimulation [47] makes it tempting to speculate that HCV-infection can also, through TLR activation, stimulate IL-7 production by the liver. Indeed, non-lymphopenic HCV-infected patients demonstrate similar IL-7 plasma levels than lymphopenic HIV-infected individuals [33, 48] suggesting that most of the IL-7 production in untreated HCV-infected patients was not linked to circulating T-cell counts. The reduction of IL-7 plasma levels while lymphocytopenia establishes under IFNa therapy, the absence of a correlation between IL-7 plasma levels and CD127 expression and the concomitance of decreases in IL-7 plasma levels and HCV viral load under therapy suggest that viremia might be driving IL-7 production before initiation of therapy. Our data suggest that, before initiation of IFNa therapy, actively replicating HCV leads to the overproduction of IL-7. Subsequent reduction of IL-7 production upon initiation of therapy probably reflects the elimination of IL-7 producing HCV-infected hepatocytes. This sudden reduction of IL-7 plasma levels may lead to diminished thymopoiesis. The fact that IL-7 plasma levels did not reach normal levels when HCV became undetectable may suggest that, after the initial decline that follows the drop in viremia, IL-7 plasma levels were regulated, as in HIVinfected patients [33] and in IFNa-treated SIV-infected rhesus macaques [30] , as a consequence of lymphocytopenia through either reduced consumption or increased production in lymphoid organs [49] . Future studies with a longer follow-up period, in particular after the end of IFNa therapy and recovery from lymphocytopenia are required to further elucidate this point.