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.
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