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Sacchi P.,University of Pavia | Cima S.,University of Pavia | Corbella M.,University of Pavia | Comolli G.,Molecular and Virology Unit | And 12 more authors.
Digestive and Liver Disease | Year: 2015

Background: Liver fibrosis is accelerated in patients co-infected with human immunodeficiency virus and hepatitis C viruses. Aims: We investigated the correlation between liver fibrosis, immune activation and microbial translocation. Methods: This cross-sectional study included patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) mono-infections, HIV/HCV co-infection, and healthy controls (20 subjects/group). Peripheral blood was analysed to determine the levels of Forkhead box 3 (Foxp3) T cells, TGF-β1, CD14 (soluble and surface isoforms), IL-17 and bacterial translocation products. These measurements were correlated to the severity of liver fibrosis, measured with the FIB-4 score and transient elastography. Results: Foxp3T cell levels were significantly elevated in HIV mono-infected and co-infected groups (p<. 0.0005). FIB-4 and liver stiffness values inversely correlated with TGF-β1 (p= 0.0155 and p= 0.0498). Bacterial DNA differed significantly in the HIV-positive compared to the other groups: HIV/HCV co-infected subjects had significantly higher serum levels of bacterial translocation products, CD14, and IL-17 levels (p<. 0.001). Conclusions: Fibrosis stage in HIV/HCV co-infection may be influenced by immune activation due either by viral infections or to bacterial translocation. © 2014 Editrice Gastroenterologica Italiana S.r.l. Source

Di Maio V.C.,University of Rome Tor Vergata | Cento V.,University of Rome Tor Vergata | Di Paolo D.,University of Rome Tor Vergata | Aragri M.,University of Rome Tor Vergata | And 46 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2016

Objectives: This study aims to evaluate the reliability and clinical utility of NS3 sequencing in hepatitis C virus (HCV) 1-infected patients who were candidates to start a PI-containing regimen. Methods: NS3 protease sequencing was performed by in-house-developed HCV-1 subtype-specific protocols. Phylogenetic analysis was used to test sequencing reliability and concordance with previous genotype/subtype assignment by commercial genotyping assays. Results: Five hundred and sixty-seven HCV plasma samples with quantifiable HCV-RNA from 326 HCV-infected patients were collected between 2011 and 2014. Overall, the success rate of NS3 sequencing was 88.9%. The success rate between the two subtype protocols (HCV-1a/HCV-1b) was similarly high for samples with HCV-RNA > 3 log IU/mL (>92% success rate), while it was slightly lower for HCV-1a samples with HCV-RNA ≤ 3 log IU/mL compared with HCV-1b samples. Phylogenetic analysis confirmed the genotype/subtype given by commercial genotyping assays in 92.9% (303/326) of cases analysed. In the remaining 23 cases (7.1%), 1 was HCV-1g (previously defined as subtype 1a), 1 was HCV-4d (previously defined as genotype 1b) and 1 was HCV-1b (previously defined as genotype 2a/2c). In the other cases, NS3 sequencing precisely resolved the either previous undetermined/discordant subtype 1 or double genotype/subtype assignment by commercial genotyping assays. Resistance-associated variants (RAVs) to PI were detected in 31.0% of samples. This prevalence changed according to PI experience (17.1% in PI-naive patients versus 79.2% in boceprevir/telaprevir/simeprevir-failing patients). Among 96 patients with available virological outcome following boceprevir/telaprevir treatment, a trend of association between baseline NS3 RAVs and virological failure was observed (particularly for HCV-1a-infected patients: 3/21 failing patients versus 0/22 achieving sustained virological response; P = 0.11). Conclusions: HCV-NS3 sequencing provides reliable results and at the same time gives two clinically relevant pieces of information: A correct subtype/genotype assignment and the detection of variants that may interfere with the efficacy of PI. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Fogh I.,Kings College London | D'Alfonso S.,The Interdisciplinary Center | Gellera C.,Unit of Genetics of Neurodegenerative and Metabolic Diseases | Ratti A.,University of Milan | And 15 more authors.
Neurobiology of Aging | Year: 2011

We have attempted to replicate a recently reported association of polymorphism rs10260404, in the Dipeptidyl-peptidase 6 gene (DPP6), with susceptibility to amyotrophic lateral sclerosis (ALS) in a large independent Italian cohort of 904 cases and 1036 controls. Minor allele frequency was 0.38 in cases and 0.39 in controls and no evidence of association with ALS was observed (P= 0.638). Our negative results agree with those recently reported in additional Polish and Italian cohorts. © 2009 Elsevier Inc. Source

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