Direct‐acting antivirals (DAAs) have transformed traditional treatment options for hepatitis C virus (HCV) infection. DAA combinations have been shown to be highly effective in reducing the burden of chronic HCV infection in clinical trials and have been recommended by the European Association for the Study of the Liver (EASL) treatment guidelines. This review examines the results of second‐generation DAA combinations in real‐life clinical practice in patients with genotypes 1‐3 and in those co‐infected with HIV (real‐world data in genotypes 4‐6 are rare). Second generation DAAs (sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir, sofosbuvir plus velpatasvir, glecaprevir plus pibrentasvir, grazoprevir plus elbasvir) have very high SVR rates and good safety profiles, higher resistance barriers and are more convenient. Real‐world data in all 3 genotypes generally support the EASL guidelines and high overall sustained virological response rates are reported with recommended regimens. However, real‐world data are only available for sofosbuvir plus daclatasvir, sofosbuvir/ledipasvir, ombitasvir/paritaprevir/ritonavir plus dasabuvir. Furthermore, because of the existing level of evidence, it is difficult to define optimal regimens based on real‐world data (ie, treatment duration, when to include ribavirin and options for patients with cirrhosis). The real‐life challenges of managing HIV‐coinfected patients are also discussed showing the additional burden of avoiding drug–drug interactions between DAAs and antiretrovirals.
direct‐acting antiviral, hepatitis C, real‐world, sustained virological response