Hépatite C

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hepatitis C virus infection impacts work productivity and fatigue: An epidemiologic real-life study

Introduction and Objective: Hepatitis C virus (HCV) infection and treatment impact the patient's daily life and work productivity. Until recently, treatments were associated with side effects and insufficient virologic and hepatic results.This study evaluated fatigue, work productivity, and treatment modalities in patients with HCV infection. Materials and methods: This cross-sectional, non-interventional, multicenter study was conducted in real-life settings between March and December 2015 at 109 sites in France. Results: Data from 1269 patients were evaluable. The mean patient age was 55.8 ± 12.5 years; 53.3% (676) patients were male. A total of 80.1% (1015) of patients were Caucasian and 62.3% (791) had a genotype 1 infection, 34.2% (433) had at least one comorbidity and 15.6% (198) had ≥1 clinical sign/symptom. Illicit drug use was the main route of HCV transmission and accounted for 36.8% (466) of all infections. Fibrosis stage F0/F1 was reported in 41.4% (525) of patients. A majority of patients (60.4%, 764) had never been treated. In patients previously treated, 85.8% (430) received ribavirin and pegylated interferon and only 13.4% (67) direct-acting antivirals.The mean percent of global impairment due to health was highest (34.8 ± 30.9%) in patients 18–45 years of age. The prevalence of active employed patients with a total fatigue score ≥ its median value (45/160) was 38.6%. The mean percent work time missed due to health was 9.6 ± 23.6% for working patients of 18–45 years of age and 7.3 ± 21.8% for working patients of 45–65 years of age. The mean overall prevalence of employed patients with impairment due to health issues was 21.8 ± 26.8%. The prevalence of patients with a reduced work activity of ≥50% due to their health status was 32.1%. Conclusion: These data reinforce the request for improved disease management in France, allowing patients with HCV infection to increase work productivity, reduce fatigue, and, hopefully, cure their disease

Impact de l'Hépatite Delta sur la fibrose hépatique mesurée par élastométrie impulsionnelle

Date du colloque&nbsp;: 10/2008</p

Impact of co infection with B+Delta viruses on liver fibrosis measured by transient elastography or FibroMeter

Date du colloque&nbsp;: 03/2009</p

Impact of B+Delta viruses co infection on the liver stiffness measurement (LSM) by transient elastography

Date du colloque&nbsp;: 04/2008</p

FIG4 is a hepatitis C virus particle-bound protein implicated in virion morphogenesis and infectivity with cholesteryl ester modulation potential

There is growing evidence that virus particles also contain host cell proteins, which provide viruses with certain properties required for entry and release. A proteomic analysis performed on double-gradient-purified hepatitis C virus (HCV) from two highly viraemic patients identified the phosphatidylinositol 3,5-bisphosphate 5-phosphatase FIG4 (KIAA0274) as part of the viral particles. We validated the association using immunoelectron microscopy, immunoprecipitation and neutralization assays in vitro as well as patient-derived virus particles. RNA interference-mediated reduction of FIG4 expression decreased cholesteryl ester (CE) levels along with intra- and extracellular viral infectivity without affecting HCV RNA levels. Likewise, overexpressing FIG4 increased intracellular CE levels as well as intra- and extracellular viral infectivity without affecting viral RNA levels. Triglyceride levels and lipid droplet (LD) parameters remained unaffected. The 3,5-bisphosphate 5-phosphatase active site of FIG4 was found to strongly condition these results. Whilst FIG4 was found to localize to areas corresponding to viral assembly sites, at the immediate vicinity of LDs in calnexin-positive and HCV core-positive regions, no implication of FIG4 in the secretory pathway of the hepatocytes could be found using either FIG4-null mice, in vitro morphometry or functional assays of the ERGIC/Golgi compartments. This indicates that FIG4-dependent modulation of HCV infectivity is unrelated to alterations in the functionality of the secretory pathway. As a result of the documented implication of CE in the composition and infectivity of HCV particles, these results suggest that FIG4 binds to HCV and modulates particle formation in a CE-related manner

Efficacy and tolerance of a combination of tenofovir disoproxil fumarate plus emtricitabine in patients with chronic hepatitis B: A European multicenter study

Background and aims: The combination of tenofovir disoproxil fumarate (TDF) plus emtricitabine (FTC) is used extensively to treat HIV infection and also has potent activity against hepatitis B virus (HBV) infection. The aim of this study was to assess the efficacy and tolerance of TDF + FTC in patients with chronic hepatitis B (CHB). Methods: Seventy eight consecutive CHB patients from five European centers were included. All started a TDF + FTC combination between October 2005 and March 2010. Virological, biochemical, and clinical data were recorded during follow-up. Tolerance was also monitored. Patients were classified into either treatment simplification (TS), where efficacy of the previous treatment was obtained at TDF + FTC initiation, and treatment intensification (TI), where the previous line of therapy had failed. Results: TDF + FTC was given as a TI to 54 patients (69%) and as a TS to 24(31%). Among patients with TI, 83% were males. The median baseline HBV-DNA was 4.4 log(10) IU/mL, and median alanine-transaminase (ALT) was 1.10 x ULN. Sixty percent were HBeAg positive, 47% had significant fibrosis ( Conclusions: After a median follow-up of >76 weeks, the TDF + FTC combination showed encouraging antiviral efficacy and a good safety profile in all patients with CHB. TDF + FTC may represent an interesting clinical option to simplify therapy and increase the barrier to resistance, which should be assessed in the long term. (C) 2011 Elsevier B.V. All rights reserved

Long-term Efficacy of Interferon-Free Antiviral Treatment Regimens in Patients With Hepatitis C Virus-Associated Cryoglobulinemia Vasculitis

In small-size and short-term studies of hepatitis C virus-associated cryoglobulinemia vasculitis (HCV-CryoVas), patients had a higher rate of response and tolerance to direct-acting antiviral (DAA) agents than interferon-containing regimens. We collected follow-up data from a clinical trial to determine the long-term effectiveness and tolerance of all-oral, interferon-free DAA regimens in patients with CryoVas

Efficacy and Safety of Sofosbuvir plus Daclatasvir for Treatment of HCV-associated Cryoglobulinemia Vasculitis.

International audienceCirculating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in about 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct acting antiviral drugs in these patients. We performed open-label, prospective, multi-center study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 years; 53.6% women) were recruited from hospitals in Paris, France from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n=32) or 24 weeks (n=9) and evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks' therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56±0.18 at baseline to 0.21±0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low memory B cells, CD4+CXCR5+ IL21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 months), no patients had a serious adverse event or relapse of vasculitis