 In spite of the positive prospect regarding response rates to DAAs, there are a number of questions to be answered as soon as possible. On the one hand, the information on efficacy and safety of the DAAs available to date is derived from clinical trials that do not reflect the circumstances of the clinical practice. In this context, clinical trials usually include a considerably low proportion of patients with certain characteristics, such as cirrhotics. Data from the French cohort CUPIC reveal that this subgroup shows a lower tolerability of TVR or BOC than that reported in pivotal clinical trials. In fact, data obtained from this cohort resulted in a change of treatment guidelines for HCV monoinfected patients published by the Spanish Agency of Medicines. On the contrary, there is evidence based on observations made within the expanded access program study HEP3002 that individuals with advanced fibrosis show a efficacy and safety profile when treated with triple therapy that is more similar to that observed in clinical trials than within the CUPIC cohort. Nevertheless, in this study, exclusion criteria and follow-up were comparable to what is applied in clinical trials. Therefore, the study population may not reflect exactly the patient profile seen in real-life. 