Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a

The aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously.Patients with symptomatic acute hepatitis C were recruited from two "fever hospitals" in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 microg/week).Between May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%-43.2%]) at three months and 41.5% (95%CI [33.0%-51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4-6 months after onset of symptoms was 15/17 = 88.2% (95%CI [63.6%-98.5%]).Spontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C

Injection Drug Use Is a Risk Factor for HCV Infection in Urban Egypt

OBJECTIVE: To identify current risk factors for hepatitis C virus (HCV) transmission in Greater Cairo. DESIGN AND SETTING: A 1:1 matched case-control study was conducted comparing incident acute symptomatic hepatitis C patients in two "fever" hospitals of Greater Cairo with two control groups: household members of the cases and acute hepatitis A patients diagnosed at the same hospitals. Controls were matched on the same age and sex to cases and were all anti-HCV antibody negative. Iatrogenic, community and household exposures to HCV in the one to six months before symptoms onset for cases, and date of interview for controls, were exhaustively assessed. RESULTS: From 2002 to 2007, 94 definite acute symptomatic HCV cases and 188 controls were enrolled in the study. In multivariate analysis, intravenous injections (OR = 5.0; 95% CI = 1.2-20.2), medical stitches (OR = 4.2; 95% CI = 1.6-11.3), injection drug use (IDU) (OR = 7.9; 95% CI = 1.4-43.5), recent marriage (OR = 3.3; 95% CI = 1.1-9.9) and illiteracy (OR = 3.9; 95% CI = 1.8-8.5) were independently associated with an increased HCV risk. CONCLUSION: In urban Cairo, invasive health care procedures remain a source of HCV transmission and IDU is an emerging risk factor. Strict application of standard precautions during health care is a priority. Implementation of comprehensive infection prevention programs for IDU should be considered

Hépatites aiguës C symptomatiques en Egypte (facteurs de risque, guérison spontanée et traitement)

Nous avons étudié les facteurs de risque actuels d'infection par le VHC en milieu urbain en Égypte; pour cela, nous avons mené une étude cas-témoins recrutant des patients présentant une infection aiguë par le VHC dans deux hôpitaux du Grand Caire, entre 2002 à 2007. Pour mieux documenter la transmission intra-familiale de l'infection à VHC, définie comme la transmission entre personnes vivant sous le même toit, nous avons comparé les séquences du VHC de cas d'hépatite C aiguë avec celles de membres de la famille virémiques. L importance relative de la transmission intra-familiale par rapport aux modes actuels de transmission a été étudiée dans la même population. Nous présentons également les résultats de suivi des patients ayant présenté une hépatite aiguë C symptomatique. Nous avons estimé la proportion de la clairance virale spontanée (SVC) après hépatite aiguë symptomatique. Les patients qui n'ont pas éliminé le virus trois mois après l'apparition des symptômes ont reçu après évaluation un traitement par interféron pégylé alfa-2a. pendant 12 semaines.Les injections intraveineuses données pour des raisons médicales (OR [IC à 95%] = 5.0 [1.2, 20.2]), les sutures chirurgicales (4.2 [1.6, 11.3]), et l usage de drogues par voie intraveineuse (7.9 [1.4, 43.5]) étaient indépendamment associés à une augmentation du risque d hépatite aiguë C. La transmission du VHC intra-familiale a contribué pour moins de 5% des nouveaux cas d'hépatite aiguë C. La clairance virale spontanée dans les 6 mois suivant l'apparition des symptômes était de 41.5% (IC à 95% = 33.0%, 51.2%). Le traitement a été associé à une réponse virologique soutenue de 88.2% (IC à 95% = 63.6%, 98.5%).PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

SNP-SNP Interactions Discovered by Logic Regression Explain Crohn's Disease Genetics

<div><p>In genome-wide association studies (GWAS), the association between each single nucleotide polymorphism (SNP) and a phenotype is assessed statistically. To further explore genetic associations in GWAS, we considered two specific forms of biologically plausible SNP-SNP interactions, ‘SNP intersection’ and ‘SNP union,’ and analyzed the Crohn's Disease (CD) GWAS data of the Wellcome Trust Case Control Consortium for these interactions using a limited form of logic regression. We found strong evidence of CD-association for 195 genes, identifying novel susceptibility genes (e.g., <em>ISX</em>, <em>SLCO6A1</em>, <em>TMEM183A</em>) as well as confirming many previously identified susceptibility genes in CD GWAS (e.g., <em>IL23R</em>, <em>NOD2</em>, <em>CYLD</em>, <em>NKX2-3</em>, <em>IL12RB2</em>, <em>ATG16L1</em>). Notably, 37 of the 59 chromosomal locations indicated for CD-association by a meta-analysis of CD GWAS, involving over 22,000 cases and 29,000 controls, were represented in the 195 genes, as well as some chromosomal locations previously indicated only in linkage studies, but not in GWAS. We repeated the analysis with two smaller GWASs from the Database of Genotype and Phenotype (dbGaP): in spite of differences of populations and study power across the three datasets, we observed some consistencies across the three datasets. Notable examples included <em>TMEM183A</em> and <em>SLCO6A1</em> which exhibited strong evidence consistently in our WTCCC and both of the dbGaP SNP-SNP interaction analyses. Examining these specific forms of SNP interactions could identify additional genetic associations from GWAS. R codes, data examples, and a ReadMe file are available for download from our website: <a href="http://www.ualberta.ca/~yyasui/homepage.html">http://www.ualberta.ca/~yyasui/homepage.html</a>.</p> </div

Logic structures, frequencies, and associated Crohn's Disease odds ratios of the <i>ISX</i> gene (p-value<3.8×10⁻⁶).

<p>Logic structures, frequencies, and associated Crohn's Disease odds ratios of the <i>ISX</i> gene (p-value<3.8×10⁻⁶).</p

Forty genes with the strongest evidence for association with Crohn's Disease risk, with chromosomal locations, numbers of SNPs, approximate p-values, and Bayes factors.

**<p>indicates genes in the chromosomal locations where the WTCCC single-SNP analysis showed <b>strong</b> evidence.</p>*<p>indicates genes in the chromosomal locations where the WTCCC single-SNP analysis showed <b>moderate</b> evidence.</p>+<p>indicates chromosomal locations are those with three or more genes in the 195 genes (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0043035#pone.0043035.s001" target="_blank">Table S1</a>) showing strong evidence in our WTCCC logic-regression-based analysis, but without strong or moderate evidence in the single-SNP analysis of WTCCC.</p

Circulating Plasmacytoid Dendritic Cells in Acutely Infected Patients with Hepatitis C Virus Genotype 4 Are Normal in Number and Phenotype

International audienceThe incidence of hepatitis C virus (HCV) genotype 4 infection in Egypt provides a unique opportunity to study the innate immune response to symptomatic acute HCV infection. We investigated whether plasmacytoid dendritic cells (pDCs) are activated as a result of HCV infection. We demonstrate that, even during symptomatic acute infection, circulating pDCs maintained a similar precursor frequency and resting phenotype, compared with pDCs in healthy individuals. Moreover, stimulation with a Toll-like receptor 9 agonist resulted in an intact inflammatory response. These data support the growing consensus that pDCs are not directly activated by HCV and therefore are viable targets for immunotherapy throughout HCV infection