The objective of this study is to identify a simplified rapid screening and linkage-to-care model for HCV among PWUD.
The study stems from a collaborative project bringing together two local Italian ...Centers for Drug Addiction and the Hepatology-Infectious Diseases Department of Lazzaro Spallanzani. A research physician analyzed the available medical records seeking to identify HCV and HIV infected patients in care in the addiction centers. Between March 2018 and January 2020 subjects were selected from among a cohort of 720 PWUD in the two Centers' care. The study comprises three steps: first, screening for HCVAb; second, the linkage to care; third, clinical assessment to treatment. The research physician recruited patients for the first two steps directly in their local addiction center. The third step was conducted in the Spallanzani. The characteristics of those subjects who adhered to the three-step study program were then compared to those of the non-adhering PWUD.
194 were known HCVAb positive patients. Of the 505 PWUD in the care of the two Centers eligible for screening, 364 were enrolled in the study. 144 resulted HCVAb positive. 269 were tested for HCVRNA. 101 underwent a full assessment. 96 patients started antiviral therapy with DAA. Patients who refused first step screening were older patients and mainly heroin users; in the second step, almost all the HIV/HCV co-infected patients agreed to a viremia test; in the third step all the HIV/HCV co-infected patients refused HCV treatment.
The study suggests an on-site specialist approach conducted directly in the addiction centers themselves starting from screening; it can bring the goal of HCV PWUD microelimination closer.
•The liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype, independently from HCV infection.•An enrichment of PD-1+Vγ9Vδ2 T-cells was observed both in the peripheral blood ...and in the liver of HCVpos patients.•HCV induced a dysregulation in IFN-γ production by intrahepatic Vγ9Vδ2 T-cells by mantaining their anti-HCV activity.
Hepatitis C virus (HCV) persistence results from inefficiencies of both innate and adaptive immune responses to eradicate the infection. A functional impairment of circulating Vγ9Vδ2 T-cells was described but few data are available on Vγ9Vδ2 T-cells in the liver that, however, represents the battlefield in the HCV/host interaction.
Aim of this work was to compare circulating and intrahepatic Vγ9Vδ2 T-cells in chronic HCV-infected patients (HCVpos) and in HCV-negative (HCVneg) subjects. Phenotypic and functional analysis was performed by flow cytometry. Anti-HCV activity was analyzed by using an in vitro autologous liver culture system.
Independently from HCV infection, the liver was enriched of Vγ9Vδ2 T-cells expressing an effector/activated phenotype. In contrast, an enrichment of PD-1 expressing Vγ9Vδ2 T-cells was observed both in the peripheral blood and in the liver of HCVpos patients, probably due to a persistent antigenic stimulation. Moreover, a lower frequency of IFN-γ producing Vγ9Vδ2 T-cells was observed in the liver of HCVpos patients, suggesting a functional impairment in the cytokine production in HCVpos liver. Despite this hypo-responsiveness, intrahepatic Vγ9Vδ2 T-cells are able to exert an anti-HCV activity after specific stimulation.
Altogether, our data show that HCV infection induced a dysregulation of intrahepatic Vγ9Vδ2 T cells that maintain their anti-HCV activity after specific stimulation. A study aimed to evaluate the mechanisms of the antiviral activity may be useful to identify new pathways able to improve Vγ9Vδ2 T-cells intrahepatic function during HCV infection.
Summary
What is known and objective
The second‐generation direct‐acting antivirals represented the first major turning point for the eradication of HCV infection in almost all settings of patients. ...However, no data were available on use in gastro‐resected patients.
Case description
We report on a gastrectomized patient with chronic hepatitis C infection. She was treated with sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks, with measurement of blood levels of the drugs. She obtained sustained virological response at week 12 and 24 without dose adjustment.
What is new and conclusion
This case report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating actual SOF/LDV bioavailability.
We describe the first reported case of treatment with direct antiviral agents in a gastrotomized patient. This report can provide information useful for clinical practice in this set of patients and can open new perspectives in evaluating Sofosbuvir/Ledipasvir bioavailability.
Objectives
HIV‐positive people have increased risk of infection‐related malignancies (IRMs) and infection‐unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on ...future IRM and IURM incidence.
Methods
People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence.
Results
A total of 15 648 people contributed 95 033 person‐years of follow‐up, of whom 610 developed 643 malignancies IRMs: 388 (60%); IURMs: 255 (40%). After adjustment, a higher IRM incidence was associated with a lower CD4 count adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL, independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5‐year period from 3.1 (95% CI 1.5–5.9) per 1000 person‐years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person‐years over the same period.
Conclusions
Demographic and HIV‐related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV‐infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV‐infected populations.
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