The aim of this study was to analyze, based on changes in multidisciplinary team meetings (MDTs), the changes in the characteristics and therapeutic management of patients with hepatitis C virus (HCV) monoinfections treated with direct-acting antivirals, across the Alsace region. These changes were studied over five successive periods between January 2015 and December 2019 in 1,753 patients. The age of patients and the proportion of those born in France decreased steadily (p<0.001). The frequency of infection through drug use ranged from 27.43% to 41.66% (p<0.001). The frequency of advanced fibrosis dropped from 86.80% to 30.45% between the first two periods, with a plateau below 40% during the subsequent periods (p<0.001). Among care facilities, the University Hospital (CHU) accounted for the majority of cases during all periods; the share of general hospitals decreased by half, and the scope of care gradually expanded to include addiction treatment centers and networks of general practitioners (p<0.001). Overall, the characteristics and management of hepatitis C changed between 2015 and 2019 in line with changes in clinical practice guidelines.