Boceprevir in the treatment of chronic hepatitis C virus infection

1Hepatology-Liver Transplantation Unit, Digestive Medicine Service, Hospital Universitari La Fe, and National Network Center for Hepatology and Gastroenterology Research, instituto de Salud Carlos iii, CiBeReHD Spain; 2CSiSP, Center for Public Health Research, Public Health Department, Generalitat Valenciana and Microbioloy Department/ institut Cavanilles, University of Valencia, Valencia, Spain; 3National Network Center for Biomedical Research in epidemiology and Public Health, instituto de Salud Carlos iii, CiBeReSP Spain

Indoor Air Quality including Respiratory Viruses

The detection of SARS-CoV-2 in indoor environments is a cause of increasing concern. In this study, three sampling methodologies have been used in order to collect SARS-CoV-2 and 17 other respiratory viruses in indoor air, combined with a new analytical process to analyze respiratory viruses. Different areas of an ophthalmological hospital were investigated for the presence of these airborne viruses. Moreover, indoor air quality (IAQ) parameters (carbon dioxide, CO2; carbon monoxide, CO; nitrogen dioxide, NO2; volatile organic compounds, VOCs; formaldehyde, HCHO; and particulate matter, PM) have been examined to study the relationship between IAQ and airborne viruses. All indoor air and sur…

New developments in the management of hepatitis C virus infection: focus on boceprevir

Chronic hepatitis C virus infection is an important public health problem, and the standard treatment (combination of pegylated interferon-α and ribavirin) has an effectiveness rate of only 40%-50%. Novel virus-specific drugs have recently been designed, and multiple compounds are under development. The approval for the clinical use of direct-acting antivirals in 2011 (boceprevir [BOC] and telaprevir, viral NS3 protease inhibitors) has increased recovery rates by up to 70%. Therefore, a highly effective treatment has been envisioned for the first time. This paper focuses on BOC and the implementation of new BOC-based treatment regimes.

Clinical relevance of genetic heterogeneity in HCV

Infection by HCV affects an estimated 170 million people worldwide and it represents one of the major causes of liver transplantation and a heavy burden to healthcare systems. As with many other RNA viruses, HCV is characterized by very high levels of genetic variation, which have been associated to differences in disease progression and efficiency of antiviral treatment. Studies show many contradictory results and little consensus on such associations. Nevertheless, some general guidelines translating research results to clinical practice have been postulated. Here, we review the main research results obtained on HCV variation so far and explore the reasons for their lack of congruence und…

Benchmark of thirteen bioinformatic pipelines for metagenomic virus diagnostics using datasets from clinical samples

AbstractMetagenomic sequencing is increasingly being used in clinical settings for difficult to diagnose cases. The performance of viral metagenomic protocols relies to a large extent on the bioinformatic analysis. In this study, the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS) initiated a benchmark of metagenomic pipelines currently used in clinical virological laboratories.MethodsMetagenomic datasets from 13 clinical samples from patients with encephalitis or viral respiratory infections characterized by PCR were selected. The datasets were analysed with 13 different pipelines currently used in virological diagnostic laboratories of participating ENNGS members. The…

A population-based screening for hepatitis C antibodies and active infection using a point-of-care test in a low prevalence area

Background Data on the true prevalence of hepatitis C virus (HCV) infection in the general population is essential. We evaluated a program implementing free universal HCV screening using a non-invasive point-of-care test (POCT) (OraQuick-HCV rapid test) in oral fluid in an urban area in Valencia, South-Eastern Spain. Methods A cross-sectional study was performed during 2015–2017. Free HCV screening was offered by regular mail to 11,500 individuals aged 18 and over, randomly selected from all census residents in the Health Department. All responding participants filled in a questionnaire about HCV infection risk factors and were tested in their tertiary Hospital. In those with a positive POC…

Overcoming drug resistance in HSV, CMV, HBV and HCV infection.

Although vaccination has provided as a very efficient preventive tool, antiviral therapy is still needed to control viral infections not avoidable by prophylaxis with vaccines; those caused by viruses for which a vaccine is available, but vaccination is not universally implemented or does not result in complete, long-term protection; and in immunocompromised individuals with reduced immune control of viral replication. After more than 50 years of the first licensing for an antiherpetic drug, novel compounds for herpes-simplex viruses and human cytomegalovirus will open new strategies for better control and management of these two recurrent viral infections. Besides, the development and use…

Genetic variability of hepatitis C virus non-structural protein 3 and virus-specific CD8+ response in patients with chronic hepatitis C.

Hepatitis C virus (HCV) variation in specific T-cell epitopes may represent a mechanism of viral persistence in chronic infection. We examined the HCV non-structural protein 3 (NS3), including the immunologically relevant epitopes HCV NS3-2 KLVALGINAV (human leukocyte antigen [HLA]-A2-restricted) and HCV NS3-1391 LIFCHSKKK (HLA-A3-restricted), in 22 HLA-A2+ patients with chronic infection. Significant amino acid variation was found in HCV NS3-2 epitope sequences when compared to the HCV-1 prototype virus. Six of the nine different HCV NS3-2 peptide variants were identified in patients with HCV NS3-2-specific CD8+ cells, detected with an HLA-A2 tetramer made with the HCV-1 prototype peptide.…

Hepatitis C virus resistance to new specifically-targeted antiviral therapy: A public health perspective

Until very recently, treatment for chronic hepatitis C virus (HCV) infection has been based on the combination of two non-viral specific drugs: pegylated interferon-α and ribavirin, which is effective in, overall, about 40%-50% of cases. To improve the response to treatment, novel drugs have been designed to specifically block viral proteins. Multiple compounds are under development, and the approval for clinical use of the first of such direct-acting antivirals in 2011 (Telaprevir and Boceprevir), represents a milestone in HCV treatment. HCV therapeutics is entering a new expanding era, and a highly-effective cure is envisioned for the first time since the discovery of the virus in 1989. H…

Cytomegalovirus reactivation in liver transplant recipients due to hepatitis C cirrhosis is associated with higher cardiovascular risk - an observational, retrospective study.

The association between cytomegalovirus (CMV) reactivation and cardiovascular risk has been reported in solid organ transplant populations; however, it has yet to be assessed in liver transplantation (LT). We aim to evaluate whether CMV reactivation is associated with cardiovascular events (CVE) in HCV-LT patients. LT patients (2010 and 2014) due to HCV cirrhosis were included. Clinically significant CMV (CS-CMV) was defined as viral load (VL) >5000 copies/ml, need of therapy or CMV disease. Baseline variables and endpoint measures (CVE, survival, severe recurrent hepatitis C, de novo tumors, and diabetes) were collected. One hundred and forty patients were included. At LT, a history of AHT…

Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6.

ABSTRACTThere is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. I…

Hepatitis C virus viral kinetics during α-2a or α-2b pegylated interferon plus ribavirin therapy in liver transplant recipients with different immunosuppression regimes

Abstract Background Predictors of sustained virological response (SVR) to antiviral therapy post-liver transplantation (LT) for chronic hepatitis C are needed. In non-transplanted patients, viral kinetics can predict SVR. Objectives To determine the early viral kinetics in LT recipients with different immunosuppression (tacrolimus – Tac- vs. cyclosporine – CsA-) during treatment with peg-IFN + RBV. Study design Prospective pilot study in HCV-1b infected patients: (LT CsA n = 8; Tac n = 8; non-LT n = 4), treated with IFN α-2a vs. α-2b (180 μg or 1.5 μg/kg, respectively) once weekly plus weight-based RBV. Median CsA or Tac baseline trough levels were 141 and 7.70 ng/mL, respectively. HCV-RNA …

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the co…

Trends for genetic variation of Hepatitis C Virus quasispecies in Human Immunodeficiency virus-1 coinfected patients

Chronic infection by Hepatitis C Virus (HCV) causes liver fibrosis, which is accelerated by unknown mechanisms in patients with HIV-1 coinfection. The evolution of HCV quasispecies in this setting of coinfection is not fully understood. To compare HCV quasispecies between HIV-HCV coinfection and HCV monoinfection, we sequenced 340 HCV clones from the HVR-1 and NS3 regions at two different time points in two groups of treatment-naive patients with HCV-1a infection: (1) HIV-HCV positive (n=6); and (2) HIV negative-HCV positive (n=3). In HCV/HIV coinfection, we found a trend for reduced HCV genetic complexity and diversity, and a trend towards reduced dN/dS ratios in the HVR-1 region, especial…

Generalized Linear Model (GLM) framework for the association of host variables and viral strains with liver fibrosis in HCV/HIV coinfected patients

Chronic hepatitis C virus (HCV) infection is the main cause of advanced and end-stage liver disease world-wide, and an important factor of morbidity and mortality in Human Immunodeficiency virus-1 (HIV-1) co-infected individuals. Whereas the genetic variability of HCV has been studied extensively in monoinfected patients, comprehensive analyses of both patient and virus characteristics are still scarce in HCV/HIV co-infection. In order to find correlates for liver damage, we sought to analyze demographic, epidemiological and clinical features of HCV/HIV co-infected patients along with the genetic makeup of HCV (viral subtypes and lineage studied by nucleotide sequencing and phylogenetic ana…

Genetic characterization of influenza viruses from influenza-related hospital admissions in the St. Petersburg and Valencia sites of the Global Influenza Hospital Surveillance Network during the 2013/14 influenza season

Abstract Background Continuous surveillance for genetic changes in circulating influenza viruses is needed to guide influenza prevention and control. Objectives To compare intra-seasonal influenza genetic diversity of hemagglutinin in influenza A strains isolated from influenza hospital admissions collected at two distinct sites during the same season. Study design Comparative phylogenetic analysis of full-length hemagglutinin genes from 77 isolated influenza A viruses from the St. Petersburg, Russian Federation and Valencia, Spain sites of the Global Influenza Hospital Surveillance Network (GIHSN) during the 2013/14 season. Results We found significant variability in A(H3N2) and A(H1N1)pdm…

Genomic medicine reaches HCV-related liver transplantation: Hopes and clinical and public health implications

Retrospective screening for SARS-CoV-2 among influenza-like illness hospitalizations: 2018-2019 and 2019-2020 seasons, Valencia region, Spain

Este artículo se encuentra disponible en la siguiente URL: https://onlinelibrary.wiley.com/doi/epdf/10.1111/irv.12899 En este artículo de investigación también participan: Juan Mollar-Maseres, Germán Schwarz-Chavarri, Sandra García-Esteban, Joan Puig-Barberà, Javier Díez-Domingo y F. Xavier López-Labrador. On 9 March 2020, the World Health Organization (WHO) Global Influenza Programme (GIP) asked participant sites on the Global Influenza Hospital Surveillance Network (GIHSN) to contribute to data collection concerning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We re-analysed 5833 viral RNA archived samples collected prospectively from hospital admissions for influenza-lik…