Despite major progresses have been made in the treatment of chronic hepatitis C, patients should always be managed with caution to avoid the side effects of therapy. Currently the choice of DAAs should be made according to viral genotypes and treatment history to avoid cross-resistance issues [8, 13]. As more safety and efficacy data are becoming available in compensated cirrhosis, antiviral therapy should be considered a priority in these patients and treatment should also be started based on possible adverse reactions and therefore related clinical implications according to age and possible pre-existing factors. In this context, all relevant clinical conditions prior of antiviral treatment should also be careful evaluated being possibly correlated to the onset of adverse events during treatment. For instance, the management of decompensated cirrhotic, could result to be more difficult to manage and to be predictable in its complications as only a few studies of DAA combinations are available [9, 12]. Despite these patients should be treated in an urgent manner, on the other hand they should be managed with caution as at now only few safety data are available for DAAs in real life on the above mentioned clinical condition. Same consideration should also be done for possible cardiovascular system adverse events in those patients having cardiac diseases, since the new antivirals seem to be related to the onset of cardiotoxicity, particularly in elder population [13, 14]. In fact, according to our results on adverse events and some literature evidences [13, 14], all patients, particularly those over 65 years, should be referred to a reference centre in case of rapid clinical deterioration. The same caution applies in the pre- and post-transplant setting where drug-to-drug interactions, kidney function and many other factors should be taken into consideration [13]. In our study, we have found a high rate of a total ADR in enrolled patients compared to previous report, particularly we had higher serious adverse events in patients undergoing Sofosbuvir/Ledipasvir, Daclatasvir/Sofosbuvir compared to those reported in published clinical trials [15] particularly in those aged over 65 years. It is of note that in those latter subjects we had the most critical ADR requiring in four cases treatment suspension due to major severe adverse events, life threatening, related to heart function (submitted papers as clinical report). Regarding common adverse events, they have been previously reported to range from 10 to 50% in several clinical trials [15]. In our study of real life we have found a percentage of about 50% with some relevant clinical condition related to mood alterations during Daclatasvir/Sofosbuvir schedule not previously reported in common adverse events at our knowledge. It also should be said that our findings on all reported adverse drug reactions could also be strictly correlated to the presence of a surveillance network based on clinician and pharmacist cooperation. Indeed, one of the most interesting results of our study is mainly the usefulness of that kind of approach to the follow-up based on a network between clinician and pharmacist. Indeed this approach may also justify the evidence of a wider and more detailed assessment of adverse reaction that patients may experience compared to other previous reported paper [12]. Further, it seems also to be really interesting and effectiveness the use of a simple survey as alerting system for clinician and therefore pharmacist for a wide understanding of possible unrecognized adverse events. Certainly, it is our opinion that without this network and that kind of approach, in a real life setting, it would be really hard to identify minor adverse events related to these antivirals that could have important impact on patients. According to previous evidences and our results on possible cardiovascular system adverse events [14–16], a well defined approach and management to this new treatment focusing on ADR according to our network may really be useful for future strategies in treatment schedule in particular setting of patients as our findings on over 65 years old seem to suggest.