Introduction: Unlike other hepatitis C virus (HCV) genotypes (GTs), patients infected with GT3 are associated with an increased risk of accelerated liver disease progression. Although early immuno-modulator therapies yielded moderate sustained virologic response (SVR) rates, treatment of GT3 patients has proven more challenging in the era of direct-acting antivirals (DAAs). Areas covered: The review provides an overview of the evolution of therapies against GT3 since the approval of the first immunomodulatory agent nearly 30 years ago. Expert opinion: A greater choice of treatment options is now available for HCV GT3-infected patients. In treatment-naïve patients with or without compensated cirrhosis, SVR rates are comparably high approaching 100% irrespective of treatment option. For treatment-experienced patients, choosing the right therapy is important, especially for those with advanced liver disease. For the few patients who fail with multiple persistent highly resistant DAA substitutions, retreatment options are limited. Additional real-world treatment comparisons are required to confirm differences in SVR in these more difficult-to-treat patients. This also includes patients infected with GT3 subtypes such as GT3b where multiple DAA-resistant substitutions occur naturally. In the absence of new drugs with non-overlapping drug-resistant profiles, an interferon-based therapy may still be beneficial in select patient populations with high-level multiple DAA-resistant substitutions.
Keywords: Daclatasvir; HCV genotype 3; NS5A; direct-acting antivirals; interferon; pibrentasvir; resistance; sofosbuvir; sustained virologic response; velpatasvir.