Direct acting antivirals can cure chronic hepatitis C virus (HCV) infection but whether they will reduce global liver disease burden is uncertain. Most chronic infections are undiagnosed and transmission has increased in recent years. The first trial of a preventive vaccine is now underway in humans at risk for HCV infection. It will test the novel hypothesis that T cell-mediated immunity alone can prevent persistent HCV infection. Another vaccine that elicits neutralizing antibodies is at an advanced stage of development. Attention is turning to the understudied question of whether direct acting antiviral (DAA) cure of chronic infection restores HCV immunity. If not, it will be important to determine if preventive vaccines can also act therapeutically to reverse immune dysfunction and protect from re-infection.
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