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The arrival of direct-acting antivirals (DAA) is transforming the way hepatitis C virus (HCV) infection is managed. Continuous HCV replication is associated with extrahepatic manifestations. “Test & treat strategies” for hepatitis C should be encouraged. First-generation DAA will soon be replaced with more potent, safer and convenient drugs. High cost of HCV therapies will result in progressive marginalization of HCV populations.The approval of the first protease inhibitors as treatment for hepatitis C virus (HCV) infection is rapidly transforming the way patients with chronic hepatitis C are managed. Treatment regimens are moving to combinations given for shortened periods, excluding poorly tolerated subcutaneous interferon, and providing rates of cure exceeding 75%. The recognition of HCV infection as a systemic disease, not limited to producing liver damage, in which extrahepatic complications play a major role as the cause of morbidity and mortality, is prompting the treatment of a growing number of HCV-infected individuals. However, new challenges are emerging, including the need to diagnose a substantial proportion of asymptomatic carriers, the risk of potentially harmful drug–drug interactions and the high cost of medications. The future will probably see a progressive marginalization of residual HCV populations, with increasing over-representation of illegal immigrants, alcohol abusers, intravenous drug users and the mentally disabled.