The hepatitis C virus (HCV) treatment landscape has rapidly changed over recent years. The development of direct-acting antiviral (DAA) agents that specifically target various steps in the HCV lifecycle has revolutionized therapeutic options for patients with HCV, with the development of highly effective and well-tolerated oral interferon-free (IFN-free) regimens.
There are several DAAs that have been approved and others that are currently in development, targeting different nonstructural HCV or host proteins that are essential for HCV replication. Data on virological response in different HCV genotypes and patients subgroups are well established in the literature, while results on clinical outcome are much more limited.
In this thesis, I will describe real-life virological and clinical outcome with DAA therapy in a large cohort of patients with HCV treated in clinical practice in the Veneto Region. For this purpose, we have used the NAVIGATORE web-platform that is recording and monitoring all HCV-DAA based treatments in the Veneto region and we have assessed virological and clinical outcomes of DAAs treatment in 3 subgroups of patients: 1) HCV infected cirrhotics (both
compensated and decompensated) to clarify drugs efficacy and clinical outcomes, including long term benefits of treatment, 2) Patients with extrahepatic manifestations due to HCV and 3) patients with HCV aged > 70 years.
Our analysis has been based on a cohort of 2946 cirrhotic patients. DAAs were safe and efficacious in these patients, including those with advanced, or decompensated cirrhosis. SVR rates for most genotypes were excellent, but the initially used Sofosbuvir plus Ribavirin regimens were suboptimal in HCV-1 and HCV-3 infected patients. Efficacy was not significantly affected by common comorbidities but it was reduced in patients with Child B cirrhosis. Severe adverse event were unusually: tolerability and safety were excellent in patients with Child A cirrhosis, while were reduced in Child B patients, particularly when treated with Ribavirin containing regimens. Patients with decompensated cirrhosis often showed an improvement in Child scores and patients with compensated cirrhosis showed a reduced incidence of complications, compared to the expected rates in the natural history of untreated disease. The “de novo” incidence of HCC was also reduced during and after DAA and the incidence of HCC recurrence not increased during and after DAAs. A subgroup of patients developed an aggressive type of HCC during therapy, and this was more frequent in non-responders, an
observation that certainly deserves further evaluation. Extrahepatic manifestations of HCV infection also improved with successful antiviral therapy. Moreover, a sub-analysis in a group of patients over 70 years, the “elderly group”, confirmed excellent safety and efficacy of DAAs also in this setting.