  Background: Highly effective direct-acting antiviral (DAA) regimens (90%
efficacy) are becoming available for hepatitis C virus (HCV) treatment. This
therapeutic revolution leads us to consider possibility of eradicating the
virus. However, for this, an effective cascade of care is required. Methods: In
the context of the incoming DAAs, we used a dynamic individual-based model
including a model of the people who inject drugs (PWID) social network to
simulate the impact of improved testing, linkage to care, and adherence to
treatment, and of modified treatment recommendation on the transmission and on
the morbidity of HCV in PWID in France. Results: Under the current incidence
and cascade of care, with treatment initiated at fibrosis stage $\ge$F2, the
HCV prevalence decreased from 42.8% to 24.9% [95% confidence interval
24.8%--24.9%] after 10 years. Changing treatment initiation criteria to treat
from F0 was the only intervention leading to a substantial additional decrease
in the prevalence, which fell to 11.6% [11.6%--11.7%] at 10 years. Combining
this change with improved testing, linkage to care, and adherence to treatment
decreased HCV prevalence to 7% [7%--7.1%] at 10 years and avoided 15.3%
[14.0%-16.6%] and 29.0% [27.9%--30.1%] of cirrhosis complications over 10 and
40 years respectively. Conclusion: A high decrease in viral transmission occurs
only when treatment is initiated before liver disease progresses to severe
stages, suggesting that systematic treatment in PWID, where incidence remains
high, would be beneficial. However, eradication will be difficult to achieve.
