Hepatitis C virus elimination: So close, so far?

The advent of highly effective direct-acting antivirals (DAAs) has transformed hepatitis C virus (HCV) infection into a curable disease, with cure rates exceeding 95% across viral genotypes and clinical settings. Along with simplified, short-course treatment regimens and significant advancements in diagnostic technologies, these therapeutic breakthroughs have made eliminating HCV as a public health concern, as defined by the World Health Organization, a realistic goal. However, despite this progress, global advances toward elimination have fallen short of expectations. This review examines why HCV elimination appears to be within reach yet remains elusive. First, the molecular virology of HCV and the pharmacological rationale underlying modern DAA combination therapies are summarized to highlight how complementary antiviral mechanisms and high genetic barriers to resistance enable definitive virological cure. Then, the key factors limiting the translation of individual-level cures into population-level impact are analyzed. Persistent transmission in high-risk and marginalized populations, including people who inject drugs, incarcerated individuals, and men who have sex with men, continues to drive new infections. Incomplete case identification, losses along the care cascade, reinfection in the absence of protective immunity, and the lack of a prophylactic vaccine further constrain treatment-based prevention strategies. Structural and systemic barriers, including stigma, criminalization, inequitable access to diagnostics and treatment, fragile health systems, and uneven political commitment, exacerbate these challenges, particularly in low- and middle-income countries. Eliminating HCV will require sustained political commitment, equitable scaling up of testing and treatment, integration of care into primary and community-based services, robust harm reduction interventions, and coordination.