AIM: To asses the expression of myeloid dendritic cells (CD11c+) subset during acute HCV hepatitis and its possible involvement in natural history of the infection.METHODS: We enrolled 11 patients with acute hepatitis C (AHC) (Group A), 10 patients with acute hepatitis A (AHA) (as infective control-Group B) and 10 healthy donors (group C) in this study. All patients underwent selective flow cytometry gating strategies to assess the peripheral number of the myeloid dendritic cells (mDCs)to understand the possible role and differences during acute hepatitis.RESULTS: Eight of 11 patients with acute HCV hepatitis did not show any increase of mDCs compared to healthy individuals, while a significant decrease of mDCs was found in absolute cell count (z=-2.37; P＜0.05) and percentage (z=-2.30; P＜0.05) as compared with AHA.On the contrary, The remaining three patients of the group A had a higher mDCs number and percentage as occur in group B. Interestingly, after six months, those patients did not show any increase of mDCs subset were chronically infected. while the three subjects with an increase of peripheral mDCs, as in HAV acute infection,resolved the illness.CONCLUSION: The lack of increase of mDCs during acute hepatitis C might be an important factor involved in chronicization of the infection.