Infección por el Virus de la Hepatitis C en la era de los antivirales de acción directaoptimización del diagnóstico, tratamiento y progresión de la enfermedad

Abstract

Hepatitis C Virus (HCV) infection is a major worldwide health problem with more than 71 million infected people around the world. HCV infection is characterized by progressive liver fibrosis accumulation leading to cirrhosis and hepatocellular carcinoma development in end-stages of the disease. Direct-acting antivirals (DAAs) has represented a remarkable milestone in the history of HCV treatment, since they have allowed to reach more than 90% of sustained viral response (SVR) and therefore, making more plausible the HCV global eradication. Nonetheless, in this new therapeutic scenario, it is still necessary to optimize not only the treatments and their monitoring, but also the seek for markers which allows the identification of high-risk populations. Moreover, it is important to highlight that even the high efficacy rates of DAAs, it has been estimated that approximately 80% of worldwide infected-patients are not aware of their diagnose. Thus, it is necessary to implement and optimize active screening programs in order to identify this kind of populations. In this context, the objectives of this study have been, firstly, to characterize and evaluate the impact of European mitochondrial DNA haplogroups in the outcome of HCV infection. Secondly, to analyze and describe viral dynamics and its usefulness for the optimization of treatment monitoring and duration. Finally, the last objective has been to develop a screening program that allows identifying non-diagnosed HCV infections in the city of A Coruña, and evaluating the HCV seroprevalence in this area. The results obtained showed an association between hepatic fibrosis and European haplogroups of mitochondrial DNA, thus highlighting their possible usefulness as markers for liver damage progression. According to the viral dynamics in regimens based on DAAs, a biphasic decline of HCV viral load was observed. It was characterized by a rapid decrease during first days of treatment. In addition, although the proportion of patients with undetectable viral loads at week 4 and 8 was low, all of them reached SVR. These results suggest the need of re-evaluatig viral load monitoring rules, as well as their duration in the context of new therapies with DAAs. Finally, screening program implementation showed that the seroprevalence of HCV infection in subjects born between 1960-1969 was 2.05%, and that only 29.8% of the population had been serologically tested. The prevalence of HCV infection in people who did not know their serological status was 0.26%. The results obtained have allowed an improvement in the knowledge of HCV-infection epidemiology in the city of A Coruña, and it should be considered when implementing future screening strategies in the search for the eradication of HCV infection in Spain.