Sofosbuvir/Velpatasvir for the treatment of Hepatitis C Virus infection

Hepatitis C Virus (HCV) infection is major health problem worldwide, with 150 million infected people according to recent epidemiologic estimations. The introduction of direct-acting antivirals made a revolutionary change in the management of HCV infected patients with surprisingly high rates of antiviral response, improved tolerability and reduced time of treatment. Sofosbuvir, in combination with different partner drugs, has been the molecule that led this incredible change. The last generation of SOF-based regimens, namely Sofosbuvir/Velpatasvir, represents a single tablet, once a day, pangenotypic and pan-fibrotic combination, demonstrated to be safe and effective in almost all type of HCV infected individuals. This review overviews the main clinical data of SOF/VEL registration trials, underlying the key features of this combination in terms of efficacy, safety and Patients Reported Outcomes obtained in more than 1800 HCV chronically infected subjects

HCV and Lymphoproliferation

Hepatitis C virus (HCV) infection is a serious public health problem because of its worldwide diffusion and sequelae. It is not only a hepatotropic but also a lymphotropic agent and is responsible not only for liver injury—potentially evolving to cirrhosis and hepatocellular carcinoma—but also for a series of sometimes severely disabling extrahepatic diseases and, in particular, B-cell lymphoproliferative disorders. These latter range from benign, but prelymphomatous conditions, like mixed cryoglobulinemia, to frank lymphomas. Analogously with Helicobacter pylori related lymphomagenesis, the study of the effects of viral eradication confirmed the etiopathogenetic role of HCV and showed it is an ideal model for better understanding of the molecular mechanisms involved. Concerning these latter, several hypotheses have been proposed over the past two decades which are not mutually exclusive. These hypotheses have variously emphasized the important role played by sustained stimulation of the immune system by HCV, infection of the lymphatic cells, viral proteins, chromosomal aberrations, cytokines, or microRNA molecules. In this paper we describe the main hypotheses that have been proposed with the corresponding principal supporting data

Association between mixed cryoglobulinemia, translocation (14;18), and persistence of occult HCV lymphoid infection after treatment

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MicroRNA expression in hepatitis C virus-related malignancies: A brief review

Not only is chronic hepatitis C virus (HCV) infection a major public health problem, but also it can cause hepatocellular carcinoma and, more rarely, non-Hodgkin’s lymphoma. These characteristics mean that HCV is the only virus infecting humans that is able to cause two different cancers. The fine pathogenetic and molecular mechanisms by which HCV induces these two malignancies are not completely clear. In the last decade, it has been shown that microRNAs (miRNAs), a class of 21-23-nucleotide molecules modulating post-transcriptional gene expression, make an important contribution to the pathogenesis of several cancers and are also considered highly promising biomarkers. Here, we briefly describe the current knowledge about microRNAs’ involvement in HCV-related molecular oncogenesis. We decided to focus our attention on studies fully conducted on ex vivo samples with this specific etiology, and on cultured cell lines partially or completely expressing the HCV genome. Some of the results reported in this review are controversial, possibly because of methodological issues, differences in sampling size and features, and ethnicity of patients. What is certain is that miRNAs play a remarkable role in regulating gene expression during oncogenetic processes and in viral infection. A clear understanding of their effects is fundamental to elucidating the mechanisms underlying virus-induced malignancies

Hepatitis C virus-related mixed cryoglobulinemia: is genetics to blame?

Mixed cryoglobulinemia (MC) is the extrahepatic manifestation most strictly correlated with hepatitis C virus (HCV) infection; it is a benign autoimmune and lymphoproliferative disorder that evolves to lymphoma in 5%-10% of cases. MC is reputed to be a multistep and multifactorial process whose pathogenicity is still poorly understood. It is still unknown why only some chronically infected HCV patients develop MC and only some of these exhibit systemic symptoms (MC syndrome). Several studies have investigated the pathogenetic basis of MC and the most recent ones suggest that the virus is able to trigger such a disorder only in the presence of genetic factors that are still unknown. Here, we try to clarify the complex relationship between HCV-related MC and the host's genetic background. The data that we report are heterogeneous and sometimes even conflicting. Therefore, large, multicenter studies are clearly needed. The identification of a characteristic genetic signature of cryoglobulinemic patients would be an important step toward a personalized approach in their clinical care. The new wide-ranging genomics technologies will hopefully help to resolve these complex issues