9 research outputs found
Expression of Defective Hepatitis B Virus Particles Derived from Singly Spliced RNA Is Related to Liver Disease
International audienceBackground. Defective hepatitis B virus (HBV) particles, generated from singly spliced HBV RNA, have been detected in chronic carriers of HBV. The present study was designed to quantify the expression of defective HBV (dHBV) and wild-type HBV (wtHBV) genomes in the serum of patients with HBV infection and its relation to the severity of liver disease. Methods. HBV and dHBV loads were determined by quantitative polymerase chain reaction in the serum of 89 untreated HBV-infected patients (31 coinfected with human immunodeficiency virus [HIV] type 1) with liver disease of different stages. The ratio of dHBV DNA to total (wtHBV plus dHBV) HBV DNA (dHBV/HBV ratio) was used to express data independently of the level of viral replication. Results. Despite a global correlation between dHBV and wtHBV load, the dHBV/HBV ratio ranged from 0.001% to 69%. The variation in dHBV/HBV ratio was independent of HIV coinfection, HBV genotype, and precore mutations. The mean dHBV/HBV ratio was higher in patients with severe liver necrosis and fibrosis. Conclusions. Our data indicate that an elevated dHBV/HBV ratio is associated with liver necroinflammation and fibrosis disease, suggesting a regulation of dHBV expression according to the severity of the liver disease. The dHBV/ HBV ratio may help to better define liver disease stage during HBV infection
Alcool : effets sur la santé
Les effets de l’alcool sur la santé constituent aujourd’hui encore un lourdproblème de santé publique. Le Comité francais d’éducation pour la santé(CFES) estime à 5 millions le nombre de personnes ayant en France desproblèmes médicaux, psychologiques ou sociaux en relation avec une consommationexcessive d’alcool.L’intoxication alcoolique chronique est responsable d’un excès de morbiditéet de mortalité par cancer, hépatopathie, atteinte du système nerveux centralou périphérique, maladie cardiovasculaire ou anomalies du développement,chez l’enfant exposé in utero. Les conséquences de l’usage de boissons alcooliquessur la santé dépendent toutefois de la susceptibilité du consommateur,ainsi que de son mode et surtout de son niveau de consommation.En France, le fait de consommer des boissons alcooliques (vin, bière, spiritueux{)correspond pour une majorité d’hommes et de femmes à des habitudesalimentaires ou culturelles bien ancrées, la plupart des individus ne présentantpas de problème particulier lié à cet usage. Les données épidémiologiquesrécentes suggèrent même une relation entre une consommation modéréed’alcool et un risque moindre de mortalité. L’association la plus significativeest essentiellement observée après l’âge de 50 ans, dans les pays industrialisésoù l’incidence des maladies cardiovasculaires est élevée. Il n’existe toutefoisaucun argument prouvant une relation de cause à effet.La Caisse nationale d’assurance maladie des travailleurs salariés (Cnamts), leCFES et la Mission interministérielle de lutte contre la drogue et la toxicomanie(Mildt), parties prenantes des politiques de prévention en matière deconsommation d’alcool, ont souhaité interroger l’Inserm à travers la procédured’expertise collective pour disposer des données scientifiquement validéesles plus récentes concernant les effets sur la santé de l’alcool, afind’informer la population sur les risques liés aux différents niveaux de consommationet mieux adapter les messages de prévention. Pour répondre à cetobjectif, l’Inserm a réuni un groupe pluridisciplinaire d’experts dans les domainesde l’épidémiologie, de la biologie, de la toxicologie et de la clinique desdifférentes pathologies liées à une consommation excessive d’alcool. Le groupe d’experts a structuré sa réflexion autour des questions suivantes :• Quel est le devenir de l’alcool dans l’organisme ? Comment différentsparamètres biologiques (sexe, âge, poids, patrimoine génétique) ou environnementaux(alimentation, niveaux d’exposition) influencent-ils la toxicocinétiquede l’alcool ?• Quels sont les effets d’une consommation aiguë ou chronique d’alcool surles systèmes nerveux central et périphérique, sur les fonctions cognitives ?Quels sont les mécanismes de la neurotoxicité ?• Quelles sont les conséquences d’une exposition in utero sur le développementdu fœtus (tératogénicité, fœtotoxicité) et de l’enfant ? Quels sont lesmécanismes impliqués dans les lésions fœtales ?• Quelle est la toxicité hépatique de l’alcool ? Quels en sont les mécanismesd’action (cytokines, stress oxydant{) ?• Quel est l’impact de la consommation d’alcool sur les facteurs de risque et lamorbi-mortalité cardiovasculaire ? Quelle est la relation dose-effet ?• Quels sont les risques de cancer liés à la consommation d’alcool ?• Quelles sont les susceptibilités génétiques individuelles aux maladies liées àla consommation d’alcool ?• Quelles sont les relations entre consommation d’alcool et statut nutritionnel,et corpulence ?L’interrogation des bases bibliographiques internationales a conduit à sélectionnerplus de 1 500 articles. Au cours de sept séances de travail organiséesentre les mois de novembre et mai 2001, les experts ont présenté une analysecritique et une synthèse des travaux publiés au plan international sur lesdifférents effets de la consommation d’alcool. Les trois dernières séances ontété consacrées à l’élaboration des principales conclusions et des recommandations.Enfin, les apports de l’imagerie médicale anatomique et fonctionnelledans la compréhension des lésions liées à la consommation d’alcool et lesdonnées de mortalité due à l’imprégnation alcoolique chronique en Franceont fait l’objet de communications
Efficacy of a 12-week simeprevir plus peginterferon/ribavirin (PR) regimen in treatment-naïve patients with Hepatitis C virus (HCV) genotype 4 (GT4) infection and mild-to-moderate fibrosis displaying early on-treatment virologic response
Background: HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12.
Methods: This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18–70 years with METAVIR F0–F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24.
Results: Of 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3–4 adverse events was lower in the 12-week group than in the 24-week group.
Conclusions: Our findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study
SVR12 among patients with HCV GT4 in the 12-week treatment group.
<p>SVR12 among patients with HCV GT4 in the 12-week treatment group.</p
Eligibility for 12-week simeprevir plus PR regimen according to patient baseline characteristics.
<p>Eligibility for 12-week simeprevir plus PR regimen according to patient baseline characteristics.</p
On-treatment AEs Reported During the Study Period.
<p>On-treatment AEs Reported During the Study Period.</p
Patient Demographics and Disease Characteristics at Baseline for Patients with HCV GT4 by Treatment Duration and Overall (n = 67).
<p>Patient Demographics and Disease Characteristics at Baseline for Patients with HCV GT4 by Treatment Duration and Overall (n = 67).</p
Effect of age and frequency of injections on immune response to hepatitis B vaccination in drug users
Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2) : results of a randomised, double-blind, placebo-controlled, phase 3 trial
Background Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.
Methods ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.
Findings Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36 center dot 0 (15 center dot 0-62 center dot 0) days. Vaccine efficacy was 75 center dot 2% (adjusted 95% CI 54 center dot 6-87 center dot 3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55 center dot 6%] of 3015 vs 896 [57 center dot 5%] of 1559, respectively; systemic adverse events, 1764 [58 center dot 5%] of 3015 vs 821 [52 center dot 7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.
Interpretation A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed. Funding Janssen Research & Development.
Copyright (c) 2022 The Author(s). Published by Elsevier Ltd