Caracterización epidemiológica y virológica en pacientes con infección crónica por el Virus de la Hepatitis Cimpacto en el tratamiento con antivirales de acción directa

Abstract

Hepatitis C Virus (HCV) infection is an important healthcare problem affecting more than 71 million people worldwide, and can lead to significant morbidity and mortality. Since the approval of Direct Acting Antiviral agents (DAAs), the face of HCV infection has dramatically changed. DAAs combinations are the new standard of treatment for HCV with high sustained virological response (SVR) rates of more than 90%, with a short duration and almost without adverse events. Nevertheless, in the first stages, the high price of these medications has limited the spread of a global treatment to HCV infected patients. This situation was resolved in May 2015 when the Spanish National Health Service published a Strategic Plan that established the criteria for the priorization of new DAAs treatments. Despite the high cure rates associated with new DAAs greater than 90%, there are still a proportion of patients that range between 2-10% who do not reach SVR. Among the different causes associated with the lack of response there are several factors such as the degree of liver fibrosis, prior IFN-based therapy, viral load, viral genotype or the presence of resistant mutations (RASs) located in viral genome regions which are therapeutic targets of DAAs (like NS5A). Indeed, RASs are usually associated with therapeutic failure when they appear together with other factors related to lower rates of SVR. All of these factors must be taken into account to optimize treatment choice and treatment duration, in order to ensure the best patient response. In this context, the objectives of this study were, at first, to characterize the chronic HCV infection profile in the healthcare area of A Coruña, and to evaluate the impact of the Spanish Strategic Plan in the treatment of this population. Secondly, the objectives were to assess the prevalence of baseline RASs in NS5A in patients with genotypes 1a (G1a) and 3 (G3), and to evaluate the benefits of performing a resistance study in order to optimize the current therapeutic strategies. The results obtained in the first study, indicated that the profile of chronic HCV infection in the healthcare area of A Coruña was characterized by a major prevalence of males (76,2%) with a median age of 50 ± 9.5 years, where liver cirrhosis (28.7%) and Human Immunodeficiency Virus (HIV) co-infection (60.9%) were frequent. At virological level, the virus presented high viral loads and the major genotype was 1 (66.1%), subtype 1a 41.5%, followed by G3 (16.8%). During 2015 the 52.7% of patients started treatment with an overall SVR rate higher than 96%. We did not observed significant differences between the SVR and other factors related to worse treatment response such as cirrhosis, HIV co-infection, viral genotype, or prior exposure to treatment. Of patients who initiated treatment, the 72.9% were recognized as priority according to the Spanish Strategic Plan (≥F2, transplanted or with extrahepatic manifestations), indicating that this Plan has been critical for the advance in the cure against HCV in the healthcare area of A Coruña. The results obtained in the second study, described in the healthcare area of A Coruña a low prevalence of RASs in NS5A region in patients with G1a and G3 (5.5% versus 0.0%) as well as a high proportion of patients with other factors related to lower SVR rates (78.9% for G1a and 75.8% for G3). As a result, the rates of patients harboring NS5A RASs in combination with the other factors were low, so in the vast majority of patients (G1a more than 94% and G3 100%) treatment could be optimized. Hence, all of them could be treated with standard treatments of 12 weeks without ribavirin (RBV). In conclusion, resistance studies in specific HCV-infected populations might be useful to optimize current NS5A-based therapies, so it might afford costs to the healthcare systems and it also might avoid the adverse effects related to the use of RBV.