Integrated Hepatitis C Care for People Who Inject Drugs (Heplink): Protocol for a Feasibility Study in Primary Care (Preprint)

Background: Hepatitis C virus (HCV) infection is a major cause of chronic liver disease and death. Drug use remains the significant cause of new infections in the European Union, with estimates of HCV antibody prevalence among people who inject drugs ranging from 5% to 90% in 29 European countries. In Ireland and the European Union, primary care is a key area to focus efforts to enhance HCV diagnosis and treatment among people who inject drugs. Objective: The Heplink study aims to improve HCV care outcomes among opiate substitution therapy (OST) patients in general practice by developing an integrated model of HCV care and evaluating its feasibility, acceptability, and likely efficacy. Methods: The integrated model of care comprises education of community practitioners, outreach of an HCV-trained nurse into general practitioner (GP) practices, and enhanced access of patients to community-based evaluation of their HCV disease (including a novel approach to diagnosis, that is, Echosens FibroScan Mini 430). A total of 24 OST-prescribing GP practices were recruited from the professional networks and databases of members of the research consortium. Patients were eligible if they are aged ≥18 years, on OST, and attend the practice for any reason during the recruitment period. Baseline data on HCV care processes and outcomes were extracted from the clinical records of participating patients. Results: This study is ongoing and has the potential to make an important impact on patient care and provide high-quality evidence to help GPs make important decisions on HCV testing and onward referral. Conclusions: A substantial proportion of HCV-positive patients on OST in general practice are not engaged with specialist hospital services but qualify for direct-acting antiviral drugs treatment. The Heplink model has the potential to reduce HCV-related morbidity and mortality. Registered Report Identifier: RR1-10.2196/904

HEPCARE EUROPE- A Case study of a Service Innovation Project Aiming at Improving the Elimination of HCV in Vulnerable Populations in Four European Cities

OBJECTIVES: Hepatitis C Virus (HCV) is an important cause of chronic liver disease. Among at-risk populations, access to diagnosis and treatment is challenging. We describe an integrated model of care, Hepcare Europe, developed to address this challenge. METHODS: Using a case-study approach, we describe the cascade of care outcomes at all sites. Costing analyses estimated the cost per person screened and linked to care. RESULTS: A total of 2608 participants were recruited across 218 clinical sites. HCV antibody test results were obtained for 2568(98.5%), 1074(41.8%) were antibody-positive, 687(60.5%) tested positive for HCV-RNA, 650(60.5%) were linked to care and 319(43.5%) started treatment. 196(61.4%) of treatment initiates achieved a Sustained Viral Response (SVR) at dataset closure, 108(33.9%) were still on treatment, 8(2.7%) defaulted from treatment, and 7(2.6%) had a virologic failure or died. The cost per person screened varied from Є194 to Є635, while cost per person linked to care varied from Є364 to Є2035. CONCLUSIONS: Hepcare enhanced access to HCV treatment and cure, costs were affordable in all settings, offering a framework for scale-up and reproducibility

Effects of host defense peptides B2RP, Brevinin-2GU, D-Lys-Temporin, Lys-XT-7 and D-Lys-Ascaphin-8 on peripheral blood mononuclear cells: Preliminary study

© 2017 Croatian Society of Natural Sciences. All rights reserved. Background and purpose: Host defense peptides have considerable therapeutic potential. One of the limitations for their therapeutic use is insufficient selectivity of some peptides, i.e. toxicity for eukaryotic cells. In this study, we have investigated effect of two naturally occurring and three analogs of frog skin-derived peptides on viability/proliferation of resting peripheral blood mononuclear cells and activated lymphocytes. Materials and Methods: Effect of tested peptides was assessed using MTT colorimetric assay. Concanavalin A was used as lymphocyte mitogen. Results: Brevinin-2GU induced cell death only in the highest tested concentration, whereas other peptides were not cytotoxic to resting peripheral blood mononuclear cells. Moreover, high concentrations of B2RP, DLys-Ascaphin-8 and Lys-XT-7 induced cell proliferation and this effect was more prominent in lymphocytes (p<0.05). Tested peptides had opposite effect on activated lymphocytes inhibiting proliferative response to Concanavalin A (Brevinin-2GU, B2RP and D-Lys-Temporin p<0.05). Conclusions: Tested peptides (with exception of Brevinin-2GU) didn’t show cytotoxicity toward peripheral blood mononuclear cells. Moreover, they have potential to modulate immune response by inducing proliferation of resting peripheral blood mononuclear cells and limiting proliferative response to the activation stimulus. Regarding their potent antimicrobial and low hemolytic activity this makes them good candidates for therapeutic use

Chronic hepatitis C: Conspectus of immunological events in the course of fibrosis evolution

© 2019 Baskic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. In chronically infected HCV patients emergence and evolution of fibrosis, as a consequence of virus persistence, can be considered as an indicator of disease advancement. Therefore the aim of this study was to correlate alterations of immune response in chronic HCV patients with liver histopathology. Sera cytokine levels and frequency of circulating and liver infiltrating cells were evaluated using 13plex Kit Flow Cytomix, flow cytometry and immuno-histochemistry. We found that the number of circulating T lymphocytes (including CD4+, CD8+ and Treg) and B lymphocytes, as well as DCs, was higher in patients with no fibrosis than in healthy subjects. In patients with fibrosis frequency of these cells decreased, and contrarily, in the liver, number of T and B lymphocytes gradually increased with fibrosis. Importantly, in patients with advanced fibrosis, liver infiltrating regulatory T cells and DC-SIGN+ mononuclear cells with immunosuppressive and wound-healing effector functions were abundantly present. Cytokine profiling showed predominance of proinflammatory cytokines in patients with no fibrosis and a tendency of decline in level of all cytokines with severity of liver injury. Lower but sustained IL-4 production refers to Th2 predominance in higher stages of fibrosis. Altogether, our results reveal graduall alterations of immunological parameters during fibrosis evolution and illustrate the course of immunological events through disease progression